With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.

The recurrent coronavirus outbreaks in China (SARS-CoV and its relative, SARS-CoV-2) have raised speculations that perhaps Asians are somehow more susceptible to these coronaviruses. Here, we test this possibility based on an analysis of the lung-specific expression of ACE2, which encodes the known cell-entry receptor of both SARS-CoV and SARS-CoV-2. We show that ACE2 expression is not affected during tumorigenesis, supporting that the abundant transcriptomes in cancer genomic studies can be informatively used to study ACE2 expression among diverse individuals without cancer. We find that ACE2 expression in the lung increases with age, but is not associated with sex. Further, Asians do not differ from other populations for ACE2 expression and do not harbor unique genetic polymorphisms in the ACE2 locus. Thus, beyond illustrating an innovative method for assessing the potential impacts of demographic factors for non-cancer diseases from large-scale cancer sample datasets, our statistically robust findings emphasize that individuals of all races require the same level of personal protection against SARS-CoV-2.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options

SARS-CoV2 (corona virus) has spread globally at an unprecedented rate; so far, increasing SARS-CoV2-infected individuals have been identified. Although the situation in China is improving and is currently under control, the outbreak in other countries and its pandemic management is only beginning to develop. Based on 154 SARS-CoV2 genome sequence analyses, we used receptor–ligand docking to identify one potential point mutation (V354F) on the spike structure which enhances spike binding to ACE2 receptors underlying potential super infection. Importantly, the V354F site on spike S1 had been identified in 5/10 infected French patients living in Paris, who sharing 100% identical SARS-CoV2 genomes. With Covid-19 cases increasing rapidly in France that could lead to a new explosion, we suggest that the French government should identify all potential super spreaders and treat them accordingly. In summary, our study provides on of the measures to avoid the potential second worldwide explosion of SARS-CoV2.

Biomolecular structure drives function, and computational capabilities have progressed such that the prediction and computational design of biomolecular structures is increasingly feasible. Because computational biophysics attracts students from many different backgrounds and with different levels of resources, teaching the subject can be challenging. One strategy to teach diverse learners is with interactive multimedia material that promotes self-paced, active learning. We have created a hands-on education strategy with a set of fifteen modules that teach topics in biomolecular structure and design, from fundamentals of conformational sampling and energy evaluation to applications like protein docking, antibody design, and RNA structure prediction. Our modules are based on PyRosetta, a Python library that encapsulates all computational modules and methods in the Rosetta software package. The workshop-style modules are implemented as Jupyter Notebooks that can be executed in the Google Colaboratory, allowing learners access with just a web browser. The digital format of Jupyter Notebooks allows us to embed images, molecular visualization movies, and interactive coding exercises. This multimodal approach may better reach students from different disciplines and experience levels as well as attract more researchers from smaller labs and cognate backgrounds to leverage PyRosetta in their science and engineering research. All materials are freely available at https://github.com/RosettaCommons/PyRosetta.notebooks.

Background: On Dec 19, 2019, the public health department of China reported that an outbreak of pneumonia was caused by a novel Coronavirus. The virulence of the new virus COVID-19 was much greater than either the SARs and MERSs viruses and on March 11, 2020, the World Health Department (WHO) declared a worldwide pandemic. Understanding the pathophysiology of virulence of the SARS-COV-2 virus is absolutely necessary for understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance for any current or future treatment protocols. Methodology: A comprehensive PubMed search was performed during December 20, 2019 and April 03, 2020, utilizing the words: Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S-protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal. Results: The SARS-COV-2 virus is much more virulent than either the SAR’s or MER’s virus and its ability to cause serious disease inversely corresponds to the person’s ability to produce T-cells which declines linearly with age. The ACE2 receptor binding site does not vary among different ethnic groups but do in ACE-2 expression levels. This variance in expression level may explain for different infectivity rates among men and women and predict and explain different susceptibilities to infection by different ethnic groups. Furthermore, by understanding the underlying pathophysiology one can explain and provide guidance to the clinical effectiveness of any treatment. Conclusions: The underlying pathophysiology of COVID-19 explains not only the virulence, and clinical presentation, but, explains at a molecular level the comorbidity risk factors such as hypertension, sex, and age. Ethnic and anatomic expression patterns of ACE-2 and associated pathophysiology suggests that Native Americans and Asians may be particularly susceptible to this disease.

The European Space Agency (ESA) defines as Earth observation (EO) Level 2 information product a single-date multi-spectral (MS) image corrected for atmospheric, adjacency and topographic effects, stacked with its data-derived scene classification map (SCM), whose thematic map legend includes quality layers cloud and cloud-shadow. ESA EO Level 2 product generation is an inherently ill-posed computer vision (CV) problem never accomplished to date in operating mode by any EO data provider at the ground segment. Herein, it is considered: (I) necessary not sufficient pre-condition for the yet-unaccomplished dependent problems of semantic content-based image retrieval (SCBIR) and semantics-enabled information/knowledge discovery (SEIKD) in multi-source EO big data cubes. (II) Synonym of EO Analysis Ready Data (ARD) format. (III) Equivalent to a horizontal policy for background developments in Space Economy 4.0. In compliance with the GEO-CEOS Quality Assurance Framework for EO Calibration/Validation guidelines, to contribute toward filling an analytic and pragmatic information gap from multi-sensor EO big data to timely, comprehensive and operational EO value-adding information products and services, this work presents an innovative AutoCloud+ CV software toolbox for cloud and cloud-shadow quality layer detection in ESA EO Level 2 product. In vision, spatial information dominates color information. Inspired by this true-fact, the inherently ill-posed AutoCloud+ CV software was conditioned, designed and implemented to be “universal”, meaning fully automated (no human-machine interaction is required), near real-time, robust to changes in input data and scalable to changes in MS imaging sensor’s spatial and spectral resolution specifications.

Both SARS-CoV-2 and SARS-CoV initially appeared in China and spread to other parts of the world. SARS-CoV-2 has generated a COVID-19 pandemic causing more than 6 million human deaths worldwide while the SARS outbreak quickly ended in six months with a global total of 774 reported deaths. One of the factors contributing to this stunning difference in the outcome between these two outbreaks is the inaccuracy of the RT-qPCR tests for SARS-CoV-2, which generated a large number of false-negative and false-positive test results that have misled patient management and public health policy-makers. This article presented Sanger sequencing evidence to show that the RT-PCR diagnostic protocol established in 2003 for SARS-CoV can in fact detect SARS-CoV-2 accurately due to the well-known nonspecific PCR amplification of DNAs with similar sequences. Using nested RT-PCR followed by Sanger sequencing to retest 50 patient samples collected in January, 2022 and sold as RT-qPCR positive reference confirmed 21 (42%) were false-positive. Although the other 29 positive isolates were categorized as Omicron variant by partial sequencing of the N gene, and the RBD and the NTD of the S gene, 9 (31%) showed focal to complete sequencing failure in the S gene segments due to multi-allelic SNPs. During the course of the study, an Omicron variant isolate containing a BA.1 NTD and a BA.2 RBD in its S gene was also detected. Routine partial S gene sequencing of all PCR-positive samples can timely discover multi-allelic SNPs and viral recombination in the circulating variants for investigation of their impacts on vaccine efficacies, therapeutics and diagnostics.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

As the world grapples with a pandemic with various and expanding epicenters, a flurry of medical and scientific activity has gained speed and momentum in a race to halt COVID-19. A controversial topic has been the connection between COVID-19 and the Renin-Angiotensin system (RAS). COVID-19, like Sars before it, enters by way of the Angiotensin Converting Enzyme 2 (ACE2). ACE2 is ubiquitously expressed in many tissues in the body serving as the doorway by which the virus can enter and spread causing inflammatory havoc. Demographic evidence coming out of China and other locations make it clear that the elderly and those suffering cardiovascular complications such as hypertension etc are most at risk. The connection to RAS and the demographic nature of the data coming out has led many to advance hypothesis, recommendations and even therapies based on existing RAS inhibitors and other components of the renin-Angiotensin system. It is pertinent to review the literature in the context of our understanding of the renin-angiotesnin system to allow better judgements to be made as well as lines of research initiated advancing a quick resolution to COVID-19. Covid-19 appears invincible as if dipped in the river Styx, but even Achilles had a vulnerable heel. Understanding the homeostatic balance that the coronavirus disrupts, we can discover the arrow in corona’s heel.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

Ecosystems are not merely vulnerable to climate change but, if sustainably restored and protected, are a major source of human resilience. Not only is the evidence-base for the importance of these “Nature-based Solutions” (NbS) growing rapidly, but NbS are featuring with increasing prominence in global climate change policy. Here we report on the prominence of NbS in the 141 adaptation components of the 167 Nationally Determined Contributions (NDCs) that were submitted to UNFCCC by all signatories of the Paris Agreement. In total, 103 nations include NbS in the adaptation component of their NDC, 76 nations include them in both their adaptation and mitigation component, and an additional 27 include them as part of their mitigation plans only. In other words, 130 nations—or 66% of all signatories to the Paris Agreement—have articulated intentions of working with ecosystems, in one form or another, to address the causes and consequences of climate change. However, commitments rarely translate into robust science-based targets. As climate pledges are revised in 2020, we urge the ecosystem science community to work closely with policymakers to identify meaningful adaptation targets that benefit both people and the ecosystems on which they depend.

The current focus on afforestation in climate policy runs the risk of compromising both longterm carbon storage and human adaptation. It also works against efforts to stem the tide of biodiversity loss. We outline why an emphasis on diverse, intact natural ecosystems—as opposed to tree plantations with fast-growing exotic species—will help nations deliver the goals of the Paris Agreement and much more.

Work has begun in earnest to formulate a post-2020 Global Biodiversity Framework which will outline the vision and targets for the next decade of biodiversity conservation and beyond. However, the performance of the 2011-2020 Strategic Plan for Biodiversity suggests that even a meaningful target can fail to deliver if not accompanied by fit-for-purpose indicators. Here we provide a review of how ‘protected area’ effectiveness was addressed in the 2011-2020 plan and based on this, provide recommendations for fit-for-purpose indicators that will measure how such efforts contribute to the conservation of biodiversity. Indicators need to be built on quantitative data from site-level biodiversity monitoring of species and ecosystems combined with measurements of the state of nature in near-time, informed by remote-sensed products and other technologies. Additionally, indicators need to capture whether the essential elements of good management are in place including the identification of ecological values, threats, and objectives, equitable governance, and sufficient management resources and capacity. These fit-for-purpose indicators will require multilateral collaboration to galvanize support for, and resources to develop, the necessary infrastructure to collate and store information from countries.

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

Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A₁ receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH₃ cells via upregulating the expression of adenosine A₁ receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A₁ receptor.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

Effectively mapping and monitoring rubber plantation is still changing. Previous studies have explored the potential of phenology features for rubber plantation mapping through a pixel-based approach (pixel-based phenology approach). However, in fragmented mountainous Xishuangbanna, it could lead to noises and low accuracy of resultant maps. In this study, we investigated the capability of an integrated approach by combining phenology information with an object-based approach (object-based phenology approach) to map rubber plantations in Xishuangbanna. Moderate Resolution Imaging Spectroradiometer (MODIS) data were firstly used to acquire the temporal profile and phenological features of rubber plantations and natural forests, which delineates the time windows of defoliation and foliation phases. Landsat images were then used to extract a phenology algorithm comparing three different approaches: pixel-based phenology, object-based phenology, and extended object-based phenology to separate rubber plantations and natural forests. The results showed that the two object-based approaches achieved higher accuracy than the pixel-based approach, having overall accuracies of 96.4%, 97.4%, and 95.5%, respectively. This study proved the reliability of a phenology-based rubber mapping in fragmented landscapes with a distinct dry/cool season using Landsat images. This study indicated that the object-based phenology approaches can effectively improve the accuracy of the resultant maps in fragmented landscapes.

Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (M^pro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 M^pro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 M^pro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 M^pro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.

Wetlands benefits can be summarized but are not limited to their ability to store floodwaters and improve water quality, providing habitats for wildlife and supporting biodiversity, as well as aesthetic values. Over the past few decades, remote sensing and geographical information technologies has proven to be a useful and frequent applications in monitoring and mapping wetlands. Combining both optical and microwave satellite data can give significant information about the biophysical characteristics of wetlands and wetlands` vegetation. Also, fusing data from different sensors, such as radar and optical remote sensing data, can increase the wetland classification accuracy. In this paper we investigate the ability of fusion two fine spatial resolution satellite data, Sentinel-2 and the Synthetic Aperture Radar Satellite, Sentinel-1, for mapping wetlands. As a study area in this paper, Balikdami wetland located in the Anatolian part of Turkey has been selected. Both Sentinel-1 and Sentinel-2 images require pre-processing before their use. After the pre-processing, several vegetation indices calculated from the Sentinel-2 bands were included in the data set. Furthermore, an object-based classification was performed. For the accuracy assessment of the obtained results, number of random points were added over the study area. In addition, the results were compared with data from Unmanned Aerial Vehicle collected on the same data of the overpass of the Sentinel-2, and three days before the overpass of Sentinel-1 satellite. The accuracy assessment showed that the results significant and satisfying in the wetland classification using both multispectral and microwave data. The statistical results of the fusion of the optical and radar data showed high wetland mapping accuracy, with an overall classification accuracy of approximately 90% in the object-based classification. Compared with the high resolution UAV data, the classification results give promising results for mapping and monitoring not just wetlands, but also the sub-classes of the study area. For future research, multi-temporal image use and terrain data collection are recommended.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.

Background: Microbiome-Inspired Green Infrastructure (MIGI) was recently proposed as an integrative system to promote healthy urban ecosystems, through multidisciplinary design. Specifically, MIGI is defined as nature-centric infrastructure restored and/or designed and managed to enhance health-promoting interactions between humans and environmental microbiomes, whilst sustaining microbially-mediated ecosystem functionality and resilience. MIGI also aims to stimulate a research agenda that focuses on considerations for the importance of urban environmental microbiomes. Objectives: In this paper we provide details of what MIGI entails from a bioscience and biodesign perspective, highlighting the potential dual benefits for human and ecosystem health. We present ‘what is known’ about the relationship between urban microbiomes, green infrastructure and environmental factors that may affect urban ecosystem health (ecosystem functionality and resilience as well as human health). We discuss how to start operationalising the MIGI concept based on current available knowledge, and present a horizon scan of emerging and future considerations in research and practice. We conclude by highlighting challenges to the implementation of MIGI and propose a series of workshops to discuss multi-stakeholder needs and opportunities. Discussion: This article will enable urban landscape managers to incorporate initial considerations for the microbiome in their development projects to promote human and ecosystem health. However, overcoming the challenges to operationalising MIGI will be essential to furthering its practical development. Although the research is in its infancy, there is considerable potential for MIGI to help deliver sustainable urban development driven by considerations for reciprocal relations between humans and the foundations of our ecosystems –– the microorganisms.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

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

Cloud Computing is a promising and emerging technology that is rapidly being adopted by many IT companies due to a number of benefits that it provides, such as large storage space, low investment cost, virtualization, resource sharing, etc. Users are able to store a vast amount of data and information in the cloud and access it from anywhere, anytime on a pay-per-use basis. Since many users are able to share the data and the resources stored in the cloud, there arises a need to provide access to the data to only those users who are authorized to access it. This can be done through access control schemes which allow the authenticated and authorized users to access the data and deny access to unauthorized users. In this paper, a comprehensive review of all the existing access control schemes has been discussed along with analysis. Keywords: role-based access control, attribute-based access control, attribute-based encryption

Titania is one of the most comprehensively studied nanostructures due to its widespread applications in production of catalytic, gas- sensing and corrosion- resistance materials [1]. M-polynomial of nanotubes has been vastly investigated as it produces many degree-based topological indices which are numerical parameters capturing structural and chemical properties. These indices are used in the development of quantitative structure-activity relationships (QSARs) in which the biological activity and other properties of molecules are correlated with their structure like boiling point, stability, strain energy etc of chemical compounds. In this paper, we determine M-polynomials of single-walled titanium (SW TiO2) nanotubes and recover important topological degree based indices of them to theoretically judge these nanotubes. We also use Maple to plot surfaces associated to different types of single-walled titanium (SW TiO2) nanotubes.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Recently, it was confirmed that ACE2 is the receptor of 2019-nCoV, the pathogen causing the recent outbreak of severe pneumonia in China. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. It remains unclear why it is the lung but not other tissues among which ACE2 highly expressed is mainly infected. We hypothesized that there could be some other genes playing key roles in the entry of 2019-nCoV into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of 2019-nCov than ACE2 (energy score: -15.7 vs. -6.9 [kcal/mol]). Given these observations, we suggest that AGTR2 could be a putative novel gene for the the entry of 2019-nCoV into human cells but need further confirmation by biological experiments. Finally, a number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted.

The software industry has adopted component-based software development (CBSD) to rapidly build and deploy large and complex software systems with significant savings at minimal engineering effort, cost, and time. However, CBSD encounters issues on security trust, mainly with respect to dependability attributes. A system is considered dependable when it can produce the outputs for which it was designed with no adverse effect on its intended environment. Dependability consists of several attributes that imply availability, confidentiality, integrity, reliability, safety, and maintainability. Dependability attributes must be embedded in a CBSD model to develop dependable component software. Motivated by the importance of these attributes, this paper pursues two objectives: to design a model for developing a dependable system that mitigates the vulnerabilities of software components, and to evaluate the proposed model. The model proposed in this study is labelled as developing dependable component-based software (2DCBS). To develop this model, the CBSD architectural phases and processes must be framed and the six dependability attributes embedded according to the best practice method. The expert opinion approach was applied to evaluate 2DCBS framing. In addition, the 2DCBS model was applied to the development of an information communication technology (ICT) portal through an empirical study method. Vulnerability assessment tools (VATs) were employed to verify the dependability attributes of the developed ICT portal. Results show that the 2DCBS model can be adopted to develop web application systems and to mitigate the vulnerabilities of the developed systems. This study contributes to CBSD and facilitates the specification and evaluation of dependability attributes throughout model development. Furthermore, the reliability of the dependable model can increase confidence in the use of CBSD for industries.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

Global climate change requires urgent solutions. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon, partly compensating for the anthropogenic CO₂ emissions that are a major cause of rising global temperatures. However, poorly planned and executed tree-planting could actually increase CO₂ emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose ten golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery, while simultaneously improving livelihoods. These are: i) Protect existing forest first; ii) Work together (involving all stakeholders); iii) Maximize biodiversity recovery to meet multiple goals; iv) Select appropriate areas; v) Use natural regeneration wherever possible; vi) Select species to maximise biodiversity; vii) Use resilient plant material (with appropriate genetic variability and provenance); viii) Plan ahead for infrastructure, capacity and seed supply; ix) Learn by doing (using an adaptive management approach); and x) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities and their dependence on benefits from successful reforestation programmes that restore ecosystem functioning and deliver a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is now crucial to build on the public and private interest in this topic to ensure interventions provide effective, long-term carbon sinks and maximise benefits for biodiversity and people.

The human androgen receptor (AR) is a ligand inducible transcription factor harboring an amino terminal domain (AR-NTD) hosting the ligand independent activation function. AR-NTD is intrinsically disordered and display aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence of 22 residues. The length of the polyQ sequence, as well as the presence of adjacent sequence motifs modulate this aggregation property. AR-NTD contains also a conserved sequence motif KELCKAVSVSM that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions of its conserved cysteine residue. As peptide sequences with intrinsic ability to oligomerize are reported to have an impact on the aggregation of polyQ tract, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR NTD, using Atomic Force Microscopy (AFM). Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR NTD.

Nature-based solutions (NbS) are increasingly recognised for their potential to address both the climate and biodiversity crises. These outcomes are interdependent, and both rely on the capacity of NbS to support and enhance the health of an ecosystem: its biodiversity, the condition of its abiotic and biotic elements, and its capacity to function normally despite environmental change. However, while understanding of ecosystem health outcomes of nature-based interventions for climate change mitigation is growing, the outcomes of those implemented for adaptation remain poorly understood with evidence scattered across multiple disciplines. To address this, we conducted a systematic review of the outcomes of 109 nature-based interventions for climate change adaptation using 33 indicators of ecosystem health across eight broad categories (e.g. diversity, biomass, ecosystem functioning and population dynamics). We showed that 88% of interventions with positive outcomes for climate change adaptation also reported measurable benefits for ecosystem health. We also showed that interventions were associated with a 67% average increase in local species richness. All eight studies that reported benefits in terms of both climate change mitigation and adaptation also supported ecosystem health, leading to a triple win. However, there were also trade-offs, mainly for forest management and creation of novel ecosystems such as monoculture plantations of non-native species. Our review highlights two major limitations of research to date. First, only a limited selection of metrics are used to assess ecosystem health and these rarely include key aspects such as functional diversity and habitat connectivity. Second, taxonomic coverage is poor: 67% of outcomes assessed only plants and 57% did not distinguish between native and non-native species. Future research addressing these issues will allow the design and adaptive management of NbS to support healthy and resilient ecosystems, and thereby enhance their effectiveness for meeting both climate and biodiversity targets.

A SARS-CoV receptor-binding domain (RBD) recombinant protein was developed and manufactured under current good manufacturing practices in 2016. The protein known as RBD219-N1 when formulated on Alhydrogel®, induced high-level neutralizing antibodies and protective immunity with minimal immunopathology in mice after a homologous virus challenge with SARS-CoV (MA15 strain). In this report, we examined published evidence in support of whether the SARS-CoV RBD219-N1 could be repurposed as a heterologous vaccine against Coronavirus Infectious Disease (COVID)-19. Our findings include evidence that convalescent serum from SARS-CoV patients can neutralize SARS-CoV-2. Additionally, a review of published studies using monoclonal antibodies (mAbs) raised against SARS-CoV RBD and that neutralize the SARS-CoV virus in vitro, finds that some of these mAbs bind to the receptor-binding motif (RBM) within the RBD, while others bind to domains outside this region within RBD. This information is relevant and supports the possibility of developing a heterologous SARS-CoV RBD vaccine against COVID-19, especially due to the finding that the overall high amino acid similarity (82%) between SARS-CoV and SARS-CoV-2 spike and RBD domains is not reflected in RBM region (59%). However, the high similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.

Although microgrids facilitate the increased penetration of distributed generations (DGs) and improve the security of power supplies, they have some issues that need to be better understood and addressed before realising the full potential of microgrids. This paper presents a comprehensive list of challenges and opportunities supported by a literature review on the evolution of converter-based microgrids. The discussion in this paper presented with a view to establishing microgrids as distinct from the existing distribution systems. This is accomplished by, firstly, describing the challenges and benefits of using DG units in a distribution network and then those of microgrid ones. Also, the definitions, classifications and characteristics of microgrids are summarised to provide a sound basis for novice researchers to undertake ongoing research on microgrids.

Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Recent discovery of triangular boron Nanotubes makes it a competitor of carbon in many respects. Closed forms of M-polynomial of nanotubes produce closed forms of many degree-based topological indices which are numerical parameters of the structure and, in combination, determine properties of the concerned nanotubes. In this report, we give M-polynomials of triangular boron nanotubes and recover many important topological degree-based indices of these nanotubes. We also plot surfaces associated to these nanotubes.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

This study proposes a novel hybrid machine learning approach for modeling of rainfall-induced shallow landslides. The proposed approach is a combination of an instance-based learning algorithm (k-NN) and Rotation Forest (RF), state of the art machine techniques that have seldom explored for landslide modeling. The Lang Son city area (Vietnam) is selected as a case study. For this purpose, a spatial database for the study area was constructed, and then, was used to build and evaluate the hybrid model. Performance of the model was assessed using Receiver Operating Characteristic (ROC), area under the ROC curve (AUC), success rate and prediction rate, and several statistical evaluation metrics. The results showed that the model has high performance with both the training data (AUC = 0.948) and the validation data (AUC = 0.848). The results were compared with those obtained from soft computing techniques i.e. Random Forest, J48 Decision Trees, and Multilayer Perceptron Neural Networks. Overall, the performance of the proposed model is better than those obtained from the above methods. Therefore, the proposed model is a promising tool for landslide modeling. The research result can be highly useful for land use planning and management in landslide prone areas.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

A comprehensive kinetic model of the Fischer-Tropsch synthesis (FTS) is developed in a fixed bed reactor under operating conditions (temperature, 230–235°C, pressure, 20–25 bar, gas hourly space velocity, 4000–5000 cm³(STP)/h/g_catalyst ,H₂/CO feed molar ratio, 2.1) over a Co based catalyst. Reaction rate equations based on Eley-Rideal (ER) type model for initiation step and Langmuir-Hinshelwood-Hougen-Watson (LHHW) type model for propagation and termination steps of the FTS reactions have been considered and the readsorption of olefins were taken into account. The model that was reported in the literature was modified in order to explain many significant deviations from the ASF distribution. Optimum parameters have been obtained by Genetic Algorithms (GA). The calculated activation energies to produce n-paraffins and 1-olefins were in the range of 82.24 to 90.68 kJ/mol and 100.66 to 105.24 kJ/mol, respectively. The hydrocarbon distribution in FTS reactions was satisfactorily predicted particularly for paraffins.

The Internet-of-Things (IoT) triggers new types of cyber risks. Therefore, the integration of new IoT devices and services requires a self-assessment of IoT cyber security posture. By security posture this article refers to the cybersecurity strength of an organisation to predict, prevent and respond to cyberthreats. At present, there is a gap in the state-of-the-art, because there are no self-assessment methods for quantifying IoT cyber risk posture. To address this gap, an empirical analysis is performed of 12 cyber risk assessment approaches. The results and the main findings from the analysis is presented as the current and a target risk state for IoT systems, followed by conclusions and recommendations on a transformation roadmap, describing how IoT systems can achieve the target state with a new goal-oriented dependency model. By target state, we refer to the cyber security target that matches the generic security requirements of an organisation. The research paper studies and adapts four alternatives for IoT risk assessment and identifies the goal-oriented dependency modelling as a dominant approach among the risk assessment models studied. The new goal-oriented dependency model in this article enables the assessment of uncontrollable risk states in complex IoT systems and can be used for a quantitative self-assessment of IoT cyber risk posture.

Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on the tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer, and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be up-regulated in multiple cancer types. In this study, EphaA2 and EphB4 are evaluated as target for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be an especially promising candidate for IGOS of colorectal cancer.

In our study we investigated the additive manufacturing (AM) of ceramic-based Functionally Graded Materials (FGM) by the direct AM technology Thermoplastic 3D-Printing (T3DP). Zirconia components with a varying microstructure were additively manufactured by using thermoplastic suspensions with different contents of pore forming agents (PFA) and were co-sintered defect-free. Different materials were investigated concerning their suitability as PFA for the T3DP process. Different zirconia-based suspensions were prepared and used for AM of single- and multi-material test components. All samples were sintered defect-free and in the end we could realize a brick wall-like component consisting of dense (<1% porosity) and porous (approx. 5% porosity) zirconia areas to combine different properties in one component. The T3DP opens the door to AM of further ceramic-based 4D-components like multi-color or multi-material, especially multi-functional components.

The microstructural evolution, thermodynamics and kinetics of Mo-21%Tm₂O₃ (mass fraction, %) powder mixtures during ball milling were investigated using X-ray diffraction and transmission electron microscopy. Ball milling induced Tm₂O₃ to be decomposed and then dissolved into Mo crystal. The supersaturated nanocrystalline solid solution of Mo (Tm, O) was obtained after 96 h of ball milling. The elements of Mo, Tm and O were distributed uniformly in the ball-milled particles. Based on the semi-experimental theory of Miedema, a thermodynamic model was developed to calculate the driving force of phase evolution. There was no chemical driving force to form a crystal solid solution of Tm atoms in Mo crystal or an amorphous phase because the Gibbs free energy for both processes was higher than zero. For Mo-21%Tm₂O₃, it was mechanical work, not negative heat of mixing, that provided the driving force to form supersaturated nanocrystalline Mo (Tm, O) solid solution.

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Satellite-based rainfall estimation products provide a vital alternative source of rainfall data in areas where conventional precipitation measurement is not readily available. In order to facilitate the use of these products there is the need to evaluate their accuracies. This study evaluated the accuracy of three satellite rainfall products; TMPA 3B42RT, TMPA 3B42 and CMORPH in the Pra basin (23,330 km²) of Ghana. The evaluation was through the point-to-pixel method by comparing 0.25°x 0.25° satellite grids to gauged rainfall based on gauge locations and analyzed statistically using correlation coefficient (r), bias and percent bias (pBias) as the performance verification methods. Seven (7) gauge stations with no missing data for the period of 2003-2008 was used in the evaluation. The analysis was based on daily, monthly, annual and seasonal timescales. Our results showed a good correlation between the TMPA products and the gauged data on all timescales considered. The CMORPH on the other hand showed huge overestimation at all gauge locations. The TMPA 3B42 was seen to be the best amongst the three products. The overall rainfall in the basin was well depicted by the TMPA 3B42 and 3B42RT. Although there wasn’t a perfect match between the 3B42RT and 3B42 products and the gauged rainfall, these products can be used to supplement gauged rainfall measurements in the basin and in estimation of rainfall in ungauged basins with similar characteristics.

Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodelling, cell-signalling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (Phe), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than Phe, and that PhN causes a superset of the effects caused by Phe. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with Phe, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with Phe (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo.

The systematic sampling is used as a method to get the quantitative results from the tissues and the radiological images. Systematic sampling on real line (R) is a very attractive method within which the biomedical imaging is consulted by the practitioners. For the systematic sampling on R, the measurement function (MF) is occurred by slicing the three-dimensional object equidistant systematically. The currently used covariogram model in variance approximation proposed by [28,29] is tested for the different measurement functions in a class to see the performance on the variance estimation of systematically sampled R. This study is an extension of [17], and an exact calculation method is proposed to calculate the constant λ(q,N) of confidence interval in the systematic sampling. The exact value of constant λ(q,N) is examined for the different measurement functions as well. As a result, it is observed from the simulation that the proposed MF should be used to check the performances of the variance approximation and the constant λ(q,N). Synthetic data can support the results of real data.

The paper presents the design and the implementation of different advanced control strategies that are applied to a nonlinear model of a thermal unit. A data–driven grey–box identification approach provided the physically meaningful nonlinear continuous–time model, which represents the benchmark exploited in this work. The control problem of this thermal unit is important since it constitutes the key element of passive air conditioning systems. The advanced control schemes analysed in this paper are used to regulate the outflow air temperature of the thermal unit by exploiting the inflow air speed, whilst the inflow air temperature is considered as an external disturbance. The reliability and robustness issues of the suggested control methodologies are verified with a Monte–Carlo analysis for simulating modelling uncertainty, disturbance and measurement errors. The achieved results serve to demonstrate the effectiveness and the viable application the suggested control solutions to air conditioning systems. The benchmark model represents one of the key issues of this study, which is exploited for benchmarking different model–based and data–driven advanced control methodologies through extensive simulations. Moreover, this work highlights the main features of the proposed control schemes, while providing practitioners and heating, ventilating and air conditioning engineers with tools to design robust control strategies for air conditioning systems.

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

While the knowledge about the development of understanding positive integers is rapidly growing, the development of understanding zero is not well-known. Here we tested several components of preschoolers’ understanding zero: whether they can use empty sets in numerical tasks, whether they can use empty sets soon after they understand the cardinality principle, whether they know what the word “zero” refers to, and whether they categorize zero as a number. The results show that preschoolers can handle empty sets in numerical tasks as soon as they understand the cardinality principle or even earlier, and some of them know that these sets are labeled as “zero.” However, they are unsure whether zero is a number. These results identify three components of knowledge about zero: operational knowledge, linguistic knowledge, and meta knowledge. To account for these results we propose that preschoolers might understand numbers as the properties of items or objects in a set. In this view, zero cannot be a number, because an empty set does not include any items, and the missing items cannot have any property, excluding also the number property. This model might explain why zero is handled correctly in numerical tasks, while it is not regarded to be a number.

Web-Based GIS is a platform that deals with the representation, management and storage of locational information for real-time online retrieval, viewing and manipulations. Web-based GIS incorporate all the functions of information systems: gathering, storing, retrieving, visualizing and dissemination of spatial information on the Internet. In modern-day GIS serve as vital means to not only geo-referenced locational information that are been retrieved but also the development in web-based technologies as well as there involvements in decision making processes. In recent time the increased used of GIS on the Internet have totally transformed and made three distinct changes across our GIS environment. These are: (i) how are GIS data being accessed (ii) what are modes of its transmission and (iii) what available GIS functionalities are within the environment for analysis. This paper examines the applications and technologies associated with web-based GIS architectures with an emphasis on the internet GIS based structure and case studies of GIS Web-based applications in MapInfo, Microsoft Silverlight Technology and the ArcGIS Server using ArcGIS JavaScript API.

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions > 2.5 Å and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, π-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.

This paper shows a method for pipeline leak detection using a transient-based method with MATLAB® functions. The simulation of a pipeline systems in the time domain are very complex. In the case of the dissipative model, transfer functions are hyperbolic Bessel functions. Simulating a pipeline system in the frequency domain using a dissipative model we could find an approximate transfer function with equal frequency domain response to in order get the pipeline system's time domain response. The method described in this paper can be used to detect, by comparison, to detect a leak in a pipeline system model.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

The feedback collection and analysis has remained an important subject matter since long. The traditional techniques for student feedback analysis are based on questionnaire-based data collection and analysis. However, the student expresses their feedback opinions on online social media sites, which need to be analyzed. This study aims at the development of fuzzy-based sentiment analysis system for analyzing student feedback and satisfaction by assigning proper sentiment score to opinion words and polarity shifters present in the input reviews. Our technique computes the sentiment score of student feedback reviews and then applies fuzzy-logic module to analyze and quantify student’s satisfaction at the fine-grained level. The experimental results reveal that the proposed work has outperformed the baseline studies as well as state-of-the-art machine learning classifiers.

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing post-surgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

The COVID-19 pandemic situation, disease intensity, weak healthcare facilities, unawareness, and misinformation led people to fear and anxiety in Bangladesh. This study intended to get peoples’ perception on psychosocial, socio-economic and environmental crisis amidst the pandemi. An online questionnaire was surveyed nationwide (respondents no.1066). Datasets were analyzed through the Principal Component Analysis (PCA), hierarchical Cluster Analysis (CA), Pearson’s correlation matrix (PCM), Linear regression analysis (LRA), and psychometric characteristics were included in the Classical Test Theory (CTT) analysis. There were good associations among the psychosocial, socio-economic and environmental parameters. A significant association between fear of COVID-19 with struggling healthcare system (p<0.05) was found. Also, negative association between fragile health system and government’s ability to deal with the pandemic (p<0.05) revealing poor governance. Again, a positive association of shutdown and social distancing with fear of losing life, and due to lack of health treatment (p<0.05) reveals that shut down hampers normal activities which may lead to mental and economic stress. However, a positive association of socio-economic impact of the shutdown with poor people’s suffering, the price hike of basic need, hamper of formal education (p<0.05) may lead to severe socio-economic and health crisis. There is a possibility of climate-induced disaster during/after the pandemic, which will create severe food insecurity (p<0.01). Daily wage earners and poors will suffer most by food and nutritional deficiency, and the country may face huge economic burden. Proper risk assessment and communications is needed to alleviate fear and anxiety. Thus, financial support and mental boosting is required.

Hydrogen peroxide is an important chemical of increasing demand in today’s world. Currently, the anthraquinone autoxidation process dominates the industrial production of hydrogen peroxide. Herein, hydrogen and oxygen are reacted indirectly in the presence of quinones to yield hydrogen peroxide. Owing to the complexity and multi-step nature of the process, it is advantageous to replace the process with an easier and straightforward one. The direct synthesis of hydrogen peroxide from its constituent reagents is an effective and clean route to achieve this goal. Factors such as water formation due to thermodynamics, explosion risk, and the stability of the hydrogen peroxide produced hinder the applicability of this process at an industrial level. Currently, the catalysis for the direct synthesis reaction is palladium based and the research into finding an effective and active catalyst has been ongoing for more than a century now. Palladium in its pure form, or alloyed with certain metals are some of the new generation of catalysts that are extensively researched. Additionally, to prevent the decomposition of hydrogen peroxide to water, the process is stabilised by adding certain promoters such as mineral acids and halides. A major part of today’s research in this field focusses on the reactor and the mode of operation required for synthesising hydrogen peroxide. The emergence of microreactor technology has helped in setting up this synthesis in a continuous mode, which could possibly replace the anthraquinone process in the near future. This review will focus on the recent findings of the scientific community in terms of reaction engineering, catalyst and reactor design in the direct synthesis of hydrogen peroxide.

The future of machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved in labs for the most common machining operations by using models based on equations describing the physical laws of the machining processes; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep-knowledge and models” that aid machine designers, production engineers or machinists to get the best of the machine-tools. This article proposes a methodology to reduce problems in machining by means of a simulation utility, which uses the main variables of the system&process as input data, and generates results that help in the proper decision-making and machining planification. Direct benefits can be found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter-free optimum cutting conditions and d) the right programming of cutting toolpaths at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies and are explained in the paper.

Many complex behaviours in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans multiple length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modelling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modelling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviours offers a means to take synthetic biology beyond single molecules or cells and towards the creation of systems with functions that can only emerge from collectives at multiple scales.

Virus-infected Flu is a common disease. To date, no specific drugs are available to manage the symptoms of cough, headache and sputum production. An alternative Chinese herb medicine is introduced for virus-infected Flu or similar infection. Before hospitalization, some of patients may scare for cross-infection with mild symptoms or hardly go to hospital if encountered a temporary lockdown or quarantine. Some Chinese practice self-treatment of cough, headache and sputum production by inhalation of volatile chemicals from onion and garlic. Author used to take the same alternative approach of inhalation of onion, garlic or scallions for self-treatment when suffered virus caused flu with cough, headache and sputum production at onset disease. In this article, the biomedical effects of onion and garlic are reviewed. To help patients with mild symptoms of virus infected Flu, a simple home-based treatment was suggested to self-treatment because of temporary isolation and hardly going to hospitalization. The alternative approach may also suggest for some mild virus infected respiratory diseases caused by virus at onset disease.

Background: Serious games are conceptualized as a broad topic and overlap segments of more modern forms of education: e-learning, edutainment, game-based learning, and digital game-based learning. Serious Games aligns with digitalization and the modern era and creates novel opportunities for learning and assessment in medical education. Escape rooms, a type of serious games, merge mental and physical aspects to reinforce critical skills useful in daily life. It challenges logic and reasoning and demands careful analysis of situations to correlate and solve different stages of the escape room under pressurized, timed conditions. Furthermore, it serves as an adequate environment to build problem-solving skills, communication skills, and leadership skills through the collaboration of people to achieve a common goal. The aim of this study was to investigate the applications of escape rooms in Medical Education. Method: This study investigated the applications of escape rooms in medical education. Serious games are expanding in education and have attained great relevance due to their intriguing and intrinsically motivating attributes. Within serious games, we focused on escape rooms in which participants are locked in a room, faced with puzzles that must be solved to ‘escape the room’. Compiling the data from the first 100 hits of medical application of escape rooms, we found 72 cases and categorized them by year, specialty, participants structure, simulation experience, and design. Results: We reported on escape rooms in medical education by the year in which they were reported, the medical specialty, the participant structure, grouped or individual, the experience design; real, hybrid, or digital, and the modality of the delivery. 72% of the escape rooms focused on four main areas: nursing education (25.0%), emergency medicine (22.2%), pharmacy (12.5%), and interprofessional education (12.5%). Most of the escape rooms had a group-based physical design and little attention was given to provide a detailed description of the design considerations, such as the pathway type (linear, semi-linear, open). Conclusion: Escape rooms are applied in a wide range of medical education areas. In Medical Education, group-based on-site escape rooms with a focus on nursing, emergency medicine, pharmacy and interprofessional education dominates the implementation landscape. To further advance the field, stronger emphasis on making explicit the design considerations will advance the research and inform implementations.

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.

the intermittency and variability of these permeated Distributed Generators (DGs) could critically cause many security and economy risks to distribution systems. This paper applied a certain mathematical distribution to imitate the output variability and uncertainty of DGs. And then, four risk indices EENS, PLC, EFLC and SI were established to reflect the system risk level of distribution system. For the certain mathematical distribution of the DGs' output power, a developed PEM (point estimate method)-based method was proposed to calculate these four system risk indices. In this developed PEM-based method, enumeration method was used to list the states of distribution systems, an improved PEM was presented to deal with the uncertainties of DGs and the value of load curtailment in distribution systems was calculated by an optimal power flow algorithm. Finally, the effectiveness and advantages of this proposed PEM-based method for distribution system assessment were verified by the tests of a modified IEEE 30-bus system. Simulation results have shown that this proposed PEM-based method has a high computational accuracy and highly reduced computational costs compared with other risk assessment methods and is very effective for risk assessments.

The COVID-19 pandemic has brought about unprecedented changes to human lifestyles across the world. The virus and associated social restriction measures have been linked to an increase in mental health conditions. A considerable body of evidence shows that spending time in and engaging with nature can improve human health and wellbeing. Our study explores nature’s role in supporting health during the COVID-19 pandemic. We created web-based questionnaires with validated health instruments and conducted spatial analyses in a geographic information system (GIS). We collected data on people’s patterns of nature exposure, associated health and wellbeing responses, and potential socioecological drivers such as relative deprivation, access to greenspaces, and land-cover greenness. We applied a range of statistical analyses including bootstrap resampled correlations and binomial regression models, adjusting for several potential confounding factors. We found that respondents significantly changed their patterns of visiting nature as a result of the COVID-19 pandemic. People spent more time in nature and visited nature more often during the pandemic. People generally visited nature for a health and wellbeing benefit and felt that nature helped them cope during the pandemic. Greater land-cover greenness within a 250 m radius around a respondent’s postcode was important in predicting higher levels of mental wellbeing. There were significantly more food-growing allotments within 100 m and 250 m of respondents with high mental wellbeing scores. The need for a mutually-advantageous relationship between humans and the wider biotic community has never been more important. We must conserve, restore and design nature-centric environments to maintain resilient societies and planetary health.

The early-mid Paleocene Farewell Formation is stratigraphically distributed across the southern Taranaki Basin (STB) which is also encountered within the Maui Gas Field. Using available 3D seismic and well log data, a challenging task to delineate the spatial distribution and geobody patterns of the potential reservoir sands of the formation was performed. Object based modeling coupled with sequential indicator simulation were used to analyze the spatial distribution of facies configuration and a conceptual model was developed based on the outputs from the structurally- modeled grids. The facies modeling followed a hierarchical object-based mechanism which was set to perform with constraints like channel geometry and heterogeneity within the formation. The resultant 3D geobody model showed that the distributary channels, mainly braided geobodies flowed from northeast cutting through several regional normal-fault systems to the southwest. Overbank facies was adhered to the fringe of the channels whereas the floodplain facies was at the periphery of the model. Meandering channel-sand facies were mostly observed at the center of the model flowing in a more random manner, occupying major flow directions of northwest to southwest and southeast to northwest within the model.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We have performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely 39 with major depression and 11 with bipolar disorder, compared to 42 age, sex and education matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume restricted to regions located in medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts), and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression the reductions remained significant only for the patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders mainly major depression, as compared with healthy controls.

This paper outlines evidence-based practice in the context of professionalism, and highlights the contribution evidence-based practice can make to the professional practice of higher education course managers. Implications of the changing HE landscape for the status of academics as professionals are reviewed, and evidence-based practice is proposed as a solution for both enhanced course management and to remedy perceived deprofessionalisation. Finally, questions regarding researching professional practice within one’s own institution are addressed.

The next future using machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved for the most common cases by sing models based on equations describing the physical laws dominating the machining process; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep knowledge and models” that aid the machine designer, the production engineer, or machinists to get the best of their machines. This article proposes a systematic methodology to reduce problems in machining by means of a simulation utility, which recognizes, collects and uses the main variables of the system/process as input data, and generates objective results that help in the proper decision-making. Direct benefits by such an application are found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter free optimum cutting conditions and the right programming of cutting tool path at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Over half of adult Americans now have diabetes or prediabetes and worse, this epidemic is now world-wide and shows no signs of slowing, with rates of both diabetes and diabetes-related health complications still rising. When advising patients with diabetes on food choices, many providers rely on nutrition guidelines provided by the American Diabetes Association (ADA), and these guidelines influence other recommendations across the globe. Given the alarming trends in diabetes, it is paramount to review the treatment guidelines to ensure they are based on rigorous and accepted scientific methods. Our review included the evidence cited by the ADA in support of its claims and recommendations for eating patterns to combat diabetes (see Description of Eating Patterns, Supplemental Appendix), as presented in the most current edition of the annual ADA’s Standards of Medical Care in Diabetes (2018 Standards). Our review also includes sources cited in the latest edition of the ADA’s Nutrition Therapy Recommendations for Adults with Diabetes (2014 Recommendations), which also informed the 2018 Standards. In October 2018 low carbohydrate was named as a recommended eating pattern by the ADA and European Association for the Study of Diabetes (EASD)⁵but only citations from the 2014 and early 2018 ADA documents were reviewed.

With the proliferation of locating devices, more and more raw spatial trajectories are formed, and many works enrich these raw trajectories with semantics, and mine patterns from both raw and semantic trajectories, but access control of spatial trajectories is not considered yet. We present a multi-policy secure model for semantic spatial trajectories. In our model, Mandatory Access Control, Role Based Access Control and Discretionary Access control are all enforced, separately and combined, and we represent the model semi-formally in Ontology Web Language.

Background: The aim of this study was to investigate the risk of obstructive sleep apnea (OSA) among ankylosing spondylitis (AS) patients in a nationwide population. Methods: We conducted a nationwide cohort study between 2003 and 2013 using the Taiwan National Health Insurance Research Database. The AS cohort included 2210 patients who were newly diagnosed between 2003 and 2013. Randomly selected non-AS controls were matched at a 1:4 ratio based on age, sex and index date. The endpoint of OSA was occurrence or the end of 2013. Cumulative incidences, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, comorbidities and co-medications. Multivariate analyses were performed using Cox proportional hazards model. Due to violation of the proportionality assumption, landmark analysis was conducted to explore the risk of OSA during specific follow-up periods. Results: The adjusted HR (aHR) of OSA for the AS group was 2.826 (95% C.I. = 1.727–4.625) compared to the control group. On landmark analysis, aHR was 7.919 (95% C.I. = 3.169–19.792) for AS group 0–24 months from index date, and decreased to 1.816 (95% C.I. = 0.944–3.494) at ≥ 24 months from index date. On subgroup analyses increased risks of OSA in AS group compared to the control group were found for both males and females (aHRs were 4.533 (95% C.I. = 1.441–14.262) and 2.672 (95% C.I. = 1.522–4.692) for females and males, respectively). On age stratified analysis, there was significant risk only for the 40–59 age group with aHR of 3.913 (95% C.I. = 1.890–8.102). Conclusions: A higher risk of developing OSA was found among newly diagnosed AS cohort during the 12-year follow-up period, especially within 2 years after AS index date and in the 40–59 age group.

Spatio-temporal aspects of data lead to critical information. Sensors capture data at all scales continually so it is imperative that useful information be extracted ubiquitously and regularly. Location plays a vital part by helping understand relations between datasets. It is crucial to link developmental works with spatial attributes and current challenge is to create an open platform that manages real-time sensor data and provides critical spatial analytics atop expert domain knowledge provided in the system. That is a two-faced problem where the solution tackles not only data from multiple sources but also runs data management platform, a spatial data infrastructure(SDI) as backbone framework able to harness sensor web(SW). The paper proposes development of such a globally shared open spatial expert system(ES), SmaCiSENS, a first of a kind geo-enabled knowledge based(KB) ES for multiple fields, smarter cities to climate modeling. SmaCiSENS is integration of SW and SDI with domain KB on data and problems, ready to infer solutions. The paper describes an architecture for semantic enablement for SW, SDI; connect interfaces, functions of SDI and SW, and sensor data application program interfaces (APIs) to better manage climate modeling, geohazard, global changes, and other vital areas of attention and action.

Indoor positioning based on the received signal strength (RSS) of the WiFi signal has become the most popular solution for indoor localization. In order to realize the rapid deployment of indoor localization systems, solutions based on crowdsourcing have been proposed. However, compared to conventional methods, crowdsourced RSS values are more erroneous and can result in large localization errors. To mitigate the negative effect of the erroneous measurements, a graph-based semi-supervised learning (G-SSL) method is used to exploit the correlation between the RSS values at nearby locations to estimate an optimal RSS value at each location. Before using the G-SSL method, the Linear Regression (LR) algorithm is proposed to solve the device diversity problem in crowdsourcing system. Since the spatial distribution of the APs is sparse, the Compressed Sensing (CS) method is applied to precisely estimate the location of the APs. Based on the location of the APs and a simple signal propagation model, the RSS difference between different locations is calculated and used as an additional constraint to improve the performance of G-SSL. Furthermore, to exploit the sparsity of the weights used in the G-SSL, we use the CS method to reconstruct these weights more accurately and make a further improvement on the performance of the G-SSL. Experimental results show improved results in terms of the smoothness of the radio map and the localization accuracy.

The comprehensibility of good predictive models learned from high-dimensional gene expression data is attractive because it can lead to biomarker discovery. Several good classifiers provide comparable predictive performance but differ in their abilities to summarize the observed data. We extend a Bayesian Rule Learning (BRL-GSS) algorithm, previously shown to be a significantly better predictor than other classical approaches in this domain. It searches a space of Bayesian networks using a decision tree representation of its parameters with global constraints, and infers a set of IF-THEN rules. The number of parameters and therefore the number of rules are combinatorial to the number of predictor variables in the model. We relax these global constraints to a more generalizable local structure (BRL-LSS). BRL-LSS entails more parsimonious set of rules because it does not have to generate all combinatorial rules. The search space of local structures is much richer than the space of global structures. We design the BRL-LSS with the same worst-case time-complexity as BRL-GSS while exploring a richer and more complex model space. We measure predictive performance using Area Under the ROC curve (AUC) and Accuracy. We measure model parsimony performance by noting the average number of rules and variables needed to describe the observed data. We evaluate the predictive and parsimony performance of BRL-GSS, BRL-LSS and the state-of-the-art C4.5 decision tree algorithm, across 10-fold cross-validation using ten microarray gene-expression diagnostic datasets. In these experiments, we observe that BRL-LSS is similar to BRL-GSS in terms of predictive performance, while generating a much more parsimonious set of rules to explain the same observed data. BRL-LSS also needs fewer variables than C4.5 to explain the data with similar predictive performance. We also conduct a feasibility study to demonstrate the general applicability of our BRL methods on the newer RNA sequencing gene-expression data.

Summary: Studying biological systems generally relies on computational modeling and simulation, e.g., for model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML), or the Open Modeling EXchange format (OMEX). Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in Java™. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations (ODEs); Stochastic Differential Equations (SDEs); constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation: SBSCL is freely available at https://draeger-lab.github.io/SBSCL/.

The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.

The ubiquity of mobile sensors (such as GPS, accelerometer and gyroscope) together with increasing computational power have enabled an easier access to contextual information, which proved its value in next generation of the recommender applications. The importance of contextual information has been recognized by researchers in many disciplines, such as ubiquitous and mobile computing, to filter the query results and provide recommendations based on different user status. A context-aware recommendation system (CoARS) provides a personalized service to each individual user, driven by his or her particular needs and interests at any location and anytime. Therefore, a contextual recommendation system changes in real time as a user’s circumstances changes. CoARS is one of the major applications that has been refined over the years due to the evolving geospatial techniques and big data management practices. In this paper, a CoARS is designed and implemented to combine the context information from smartphones’ sensors and user preferences to improve efficiency and usability of the recommendation. The proposed approach combines user’s context information (such as location, time, and transportation mode), personalized preferences (using individuals past behavior), and item-based recommendations (such as item’s ranking and type) to personally filter the item list. The context-aware methodology is based on preprocessing and filtering of raw data, context extraction and context reasoning. This study examined the application of such a system in recommending a suitable restaurant using both web-based and android platforms. The implemented system uses CoARS techniques to provide beneficial and accurate recommendations to the users. The capabilities of the system is evaluated successfully with recommendation experiment and usability test.

Real-time energy management of a converter-based microgrid is difficult to determine optimal operating points of a storage system in order to save costs and minimise energy waste. This complexity arises due to time-varying electricity prices, stochastic energy sources and power demand. Many countries have imposed real-time electricity pricing to efficiently control demand side management. This paper presents a particle swarm optimisation (PSO) for the application of real-time energy management to find optimal battery controls of a community microgrid. The modification of the PSO consists in altering the cost function to better model the battery charging/discharging operations. As optimal control is performed by formulating a cost function, it is suitably analysed and then a dynamic penalty function in order to obtain the best cost function is proposed. Several case studies with different scenarios are conducted to determine the effectiveness of the proposed cost function. The proposed cost function can reduce operational cost by 12% as compared to the original cost function over a time horizon of 96 hours. Simulation results reveal the suitability of applying the regularised PSO algorithm with the proposed cost function, which can be adjusted according to the need of the community, for real-time energy management.

Artificial intelligence (AI) applications in different fields are developing rapidly, among which AI painting technology, as an emerging technology, has received wide attention from users for its creativity and efficiency. This study aimed to investigate the factors that influence user acceptance of the use of AIBPS by proposing an extended model that combines the Extended Technology Acceptance Model (ETAM) with the AI-based Painting System (AIBPS).A questionnaire was administered to 528 Chinese participants, using validated factor analysis data and Structural Equation Modeling (SEM) was used to test the hypotheses. The findings showed that hedonic motivation (HM) and perceived trust (PE) had a positive effect (+) on users' perceived usefulness (PU) and perceived ease of use (PEOU), while previous experience (PE) and technical features (TF) had no effect (-) on users' perceived usefulness (PU). This study provides an important contribution to the literature on AIBPS and the evaluation of systems of the same type, which helps to promote the sustainable development of AI in different domains and provides a possible space for further extension of TAM, thus helping to improve the user experience of AIBPS. The results of the study provide insights for system developers and enterprises to better motivate users to use AIBPS.

Background: Research continues to search for blood-based biomarkers sensitive to Alzheimer’s disease (AD) pathology during the initial stages when symptoms of cognitive decline are not yet apparent. A blood-based biomarker candidate is metalloprotein p53, the conformation of which was previously found to be altered in peripheral cells from individuals with mild cognitive impairment (MCI) and AD, presenting as an unfolded p53 (U-p53) conformational variant. Methods: Plasma samples from the well-characterized Australian Imaging, Biomarkers, and Lifestyle (AIBL) cohort were used to identify the clinically relevant AZ 284^® peptide, specifically present in samples from individuals with symptomatic AD. The AZ 284^® peptide, which is a marker of the U-p53 conformational variant (U-p53^AZ), was identified by immunoprecipitation (IP) with a novel U-p53 conformational variant-specific antibody followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing. Using IP-LC surface-activated chemical ionization (SACI) MS/MS analysis, the prognostic and diagnostic performance of U-p53^AZ were examined in the longitudinal AIBL cohort, including 252 plasma samples derived from 214 elderly individuals. For the prognostic analyses, U-p53^AZ levels were assessed at 36, 72, and 90 months after baseline assessment. Results: The prognostic performance of U-p53^AZ to predict the progression to AD from preclinical or prodromal AD was high, with area under the receiver operating characteristic curve (AUC) values close to or above 0.90. Furthermore, U-p53^AZ predicted the progression to AD more than 6 years prior to symptom onset with positive and negative predictive values of about 90%. Additionally, the estimated prognostic performance of U-p53^AZ was superior to other main risk factors (i.e., age, sex, and either alone or in combination with amyloid status. Furthermore, U-p53^AZ had high diagnostic performance to differentiate cognitively normal individuals from those with AD (AUC values >0.88). Conclusion: These findings support the use of U-p53^AZ as a prognostic blood-based biomarker accurately predicting the progression to AD dementia during the preclinical and prodromal stages at least 6 years before receiving the clinical diagnosis of AD dementia.

Smart sensors based on graphene field effect transistor and biologically receptors are regarded as a promising nanomaterial that could be the basis for future generations of selective real-time monitoring of target analytes and smaller electronics. So the purpose of this paper is to provide details a real-time and selective explosive sensor based on GFETs and PDA-based lipid membranes coupled with biologically inspired TNT peptide receptors. Following an introduction, this paper describes the way of fabrication of the GFETs device by investigation methods for transferring graphene sheet from Cu substrates to target substrates, which is functionalized by the TNT peptide receptors, in order to offer a system which has the capability of answering the presence of related target molecules. Field effet transistor was fabricated using graphene as a channel and monitored by the source-drain current and back-gate voltage curves in the measurement. The transport property changed compared to that of the FET made by intrinsic graphene, that is, the Dirac point position moved from positive Vg to negative Vg, indicating the transition of graphene from p-type to n-type after annealing in TNT, and GFET sensor show good sensitivity and selectivity response.

Results-Based Funding (RBF) for Reducing Emissions from Deforestation and Forest Degradation (REDD+) has become an important instrument for channeling financial resources to forest conservation activities. At the same time, much literature on conservation funding is ambiguous about the effectiveness of existing RBF schemes. Many effectiveness evaluations follow a simplified version of the principal-agent model, although in practice the relation between aid providers and funding recipients is much more complex. As a consequence, intermediary steps of conservation funding are often not accounted for effectiveness studies. This research paper aims to provide a nuanced understanding of conservation funding by analyzing the allocation of financial resources for one of the largest RBF schemes for REDD+ in the world: the Brazilian Amazon Fund. As part of this analysis, this study has built a dataset of information on Amazon Fund projects at unprecedented detail in order to accurately reconstruct the allocation of financial resources across different stakeholders (i.e. governments, NGOs, research institutions), geographies and activities. The results show that stakeholders seem to hold preferences with respect to the type of activities that they support, thereby suggesting that project owners exert much influence on how deforestation reduction is to be attained. There are evidences that governmental organizations lack financial additionality of their projects, which renders the growing share of funding to this type of stakeholder particularly worrisome. By contrast, the geographical distribution of financial resources seemed to follow a more focused rationale as financial support tends to concentrate in areas where deforestation threats are highest. Overall, the allocation of the financial resources from the Amazon Fund reflects an arbitrary support of different projects that adopt very diverging theories of change that are not primarily concerned with attaining further deforestation reductions. As projects owners exert influence on funding effectiveness to some extent, the Amazon Fund may either seek to regulate the allocation of financial resources more actively or adopt funding effectiveness evaluations that account for this influence more comprehensively.

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4,000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. At this time, our model delivers the highest predictive power on estrogen receptor agonists in the world. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules.

Hang-ju was one of five officinal varieties of Flos chrysanthemum for its edible and potable usage. Besides Flos Chrysanthemum (FL), there were also Bud Chrysanthemum (BC) and Fetal Chrysanthemum (FC) at the early and late stage of buds, respectively, in the consumption market of Hang-ju with higher prices. Whether the quality and efficiency of BC and FC was superior to FL or merely consumption misunderstandings? Three commercial products of Hongxinju, a representive cultivar of Hang-ju were studied with a GC-MS based metabolomics approach, complemented with morphology, contents of moisture and protein and the anti-oxidant activity, to reveal the metabolic alterations of violate components in Hongxinju in different flowering stage and at different processing periods. It revealed that most of the violate components were increased from fresh FC to FL, and the low-boiling fractions, inflammatory methyl arachidonate and air-polluting component of ethylbenzene were declined while the representative components with pungent flavor and cool nature of a-curcumene and (Z,Z,Z)-9,12,15-octadecatrienoic acid, vision improving carotenol of rhodopin and high-boiling fractions were elevated after processed in final FL compared with that in BC and/or FC. Though the content of protein and anti-oxidative capacity of final BC and FC were nearly equal to those of FL, in comprehensive consideration of the representative components related with the efficiency in heat cooling and vision improving, as well as the representative components related with inflammation and air-pollution, final FL was recommended other than BC and FC in the practice of medicine with the yield and quality integrated into account.

Interfaces between layers in 3D-printed elements produced by extrusion-based material deposition were investigated on both macro- and micro-scales. On the macro-scale, compression and bend tests were performed on two 3D-printable cement-based compositions (3PCs), namely C1 and C2. The influences of binder composition and time interval between layers on layer-interface strength were critically analyzed. In the context of additive manufacturing, the optimized composition C2, containing pozzolanic additives, exhibited mechanical performance superior to that of the mixture with Portland cement as the sole binder. In particular, Mixture C2 showed a less pronounced decrease in interface tensile strength. Even for time intervals between depositions of two layers as long as 1 day the loss in corresponding flexural strength was below 25%, as compared with C2 specimens tested in the perpendicular direction. In contrast, the decrease in flexural strength measured for C1 specimens amounted to over 90% for the same set of parameters. Higher porosity at the interfaces of the printed concrete layers was identified as the cause for the lower interface strengths of C1. Microscopic observations supported the findings of the macroscopic investigations. While a pronounced recovery (“self-healing”) of the porous, discontinuous interlayers was observed with increasing age for Mixture C2, in case of C1 the filling products grown in the porous interlayer were found to be non-strengthening.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

With the rapid development of satellite remote sensing technology, the volume of image datasets in many application areas is growing exponentially and the demand for Land-Cover and Land-Use change remote sensing data is growing rapidly. It is thus becoming hard to efficiently and intelligently retrieve the change information that users need from massive image databases. In this paper, content-based image retrieval is successfully applied to change detection and a content-based remote sensing image change information retrieval model is introduced. First, the construction of a new model framework for change information retrieval in a remote sensing database is described. Then, as the target content cannot be expressed by one kind of feature alone, a multiple-feature integrated retrieval model is proposed. Thirdly, an experimental prototype system that was set up to demonstrate the validity and practicability of the model is described. The proposed model is a new method of acquiring change detection information from remote sensing imagery and so can reduce the need for image pre-processing, deal with problems related toseasonal changes as well as other problems encountered in the field of change detection. Meanwhile, the new model has important implications for improving remote sensing image management and autonomous information retrieval.

Cryptography has been used from time immemorial for preserving the confidentiality of data/information in storage or in transit. Thus, cryptography research has also been evolving from the classical Caesar cipher to the modern cryptosystems based on modular arithmetic to the contemporary cryptosystems based on quantum computing. The emergence of quantum computing imposes a major threat on the modern cryptosystems based on modular arithmetic whereby, even the computationally hard problems which constitute for the strength of the modular arithmetic ciphers could be solved in deterministic time. This threat triggered post-quantum cryptography research in order to design and develop post-quantum algorithms that can withstand quantum computing attacks. This paper provides a review of the various post-quantum cryptography and, in specific, code-based cryptography research dimensions. The research directions that are yet to be explored in code-based cryptography research is another key contribution of this paper.

The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multiscale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review mathematical modelling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next-generation multiscale picture of T-cell development.