ARTICLE Download: 6| View: 26| Comments: 0 | doi:10.20944/preprints202004.0108.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: prebiotics; oligosaccharides; GOS; FOS; RNA-seq; transcriptome; differential gene expression; functional pathway analysis; Caco-2; polarized monolayers
Online: 7 April 2020 (13:37:18 CEST)
Prebiotic oligosaccharides are widely used as human and animal feed additives for their beneficial effects on the gut microbiota. However, there are limited data to assess the direct effect of such functional foods on the transcriptome of intestinal epithelial cells. The purpose of this study is to describe the differential transcriptomes and cellular pathways of colonic cells directly exposed to galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). We have examined the differential gene expression of polarized Caco-2 cells treated with GOS or FOS and their respective mock-treated cells using mRNA sequencing (RNA-seq). A total of 89 significant differentially expressed genes were identified between GOS and mock-treated groups. For FOS treatment, a reduced number of 12 significant genes were observed to be differentially expressed relative to the control group. KEGG and Gene Ontology functional analysis revealed that genes up-regulated in the presence of GOS were involved in digestion and absorption processes, fatty acids and steroids metabolism, potential antimicrobial proteins, energy-dependent and -independent transmembrane trafficking of solutes and amino acids. Using our data, we have established complementary non-prebiotic modes of action for these frequently used dietary fibers.
ARTICLE Download: 6| View: 8| Comments: 0 | doi:10.20944/preprints202004.0107.v1
Subject: Engineering, General Engineering Keywords: Discrete Multiphysics Modelling; Smoothed Particle Hydrodynamics; Lattice Spring Model; Particle-base method; Aortic Valve; Calcification; Stenosis
Online: 7 April 2020 (13:33:02 CEST)
This study proposes a 3D particle-base (discrete) multiphysics approach for modelling calcification in the aortic valve. Different stages of calcification (from mild to severe) were simulated, and their effect on the cardiac output assessed. The cardiac flow rate decreases with the level of calcification. In particular, there is a critical level of calcification below which the flow rate decreases dramatically. Mechanical stress on the membrane is also calculated. The results show that, as calcification progresses, spots of high mechanical stress appear. Firstly, they concentrate in the regions connecting two leaflets; when severe calcification is reached, then they extend to the area at the basis of the valve.
ARTICLE Download: 3| View: 7| Comments: 0 | doi:10.20944/preprints202004.0106.v1
Subject: Engineering, Civil Engineering Keywords: Meta-analysis; Effect size; Precision; Ultra-high strength concrete; Ultra-high strength fiber reinforced concrete
Online: 7 April 2020 (13:28:16 CEST)
The purpose of this study was to conduct a meta-analysis that shows the influence of fiber on ultimate compressive strength and tensile strength of ultra-high performance concrete. The internet scholarly search engines and ScienceDirect article references were used to illustrate the papers concerning the experimental investigations of mechanical properties of ultra-high strength concrete with and without fiber with clearly, completely and comparative raw data. The normal concrete test results were dismissed from this search. Seven trials were identified based on the adopted inclusion and exclusion criteria above. The meta-analysis based on standardized mean difference was carried out on the basis of a fixed-effects model for the major outcomes of the ultimate compressive and tensile properties of ultra-high performance concrete. A total of 888 test specimens were enrolled in these seven trials. The combined analysis yielded a sign of a significant improvement in ultimate compressive strength and tensile strength of ultra-high strength concrete with fiber addition of 2% by concrete volume. The summary effect size of ultimate compressive strength was 2.34 while a more improvement in term of tensile strength with effect size of 2.64. By addition fiber of 2% provides a significant benefit in mechanical properties of ultra-high performance concrete.
REVIEW Download: 2| View: 7| Comments: 0 | doi:10.20944/preprints202004.0105.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Mulberry fruit; phytochemicals; bioactive components; pharmacological properties
Online: 7 April 2020 (13:25:29 CEST)
Mulberry (Morus) cultivated worldwide in diverse agro-ecological conditions recognized as the fodder of silkworms (Bombyx mori). In India, ranging from high altitude Himalayan region to coastal region, the farmers generally cultivate these four species of mulberry (Morus alba, M. indica, M. serrata, and M. laevigata). Mulberry fruit is used in traditional medicine for several years in China and also consumed as food material in different countries of Asia and Africa. Mulberry fruit, along with high nutritious value, contains many bioactive phytochemicals that are30 of health benefits and can fight against many diseases. Many researchers attracted to this property of mulberry fruit, and they isolated bioactive polysaccharides, anthocyanins, flavonols, flavonols, phenolic acids, alkaloids, and melatonins. These compounds have antioxidant property and due to this, either in synergistically or in the pure form, these components have direct or indirect curative activity on diabetes, inflammation, tumor, hepatic diseases, immunomodulation, hyperlipidemia, neural damage, and chronic diseases. This tremendous bioactivity of mulberry fruit extract may open up a new dimension in the food and medicine industry. The present review provides recent findings of the phytochemical foundation and their bioactivities, which may encourage many researchers to explore the molecular mechanism of the biological activities which can be used for human welfare.
CASE REPORT Download: 9| View: 16| Comments: 0
Subject: Medicine & Pharmacology, Anesthesiology Keywords: Covid-19; airway extubation; aerosols; laryngeal masks; occupational health
Online: 7 April 2020 (12:33:07 CEST)
We report smooth weaning from mechanical ventilation in a patient with COVID-19. The use of the supraglottic airway device can cause fewer coughs in weaning from mechanical ventilation. This procedure avoids the aerosol-generating procedure, tracheal extubation, and is beneficial in terms of occupational health for health care workers.
REVIEW Download: 26| View: 17| Comments: 0 | doi:10.20944/preprints202004.0103.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Coronavirus; SARS-CoV-2; Medical Laboratory; Resource-limited setting, Good Laboratory Practice (GLP)
Online: 7 April 2020 (12:11:35 CEST)
The 2019 Coronavirus pandemic which was initially referred to as 2019-nCoV, was first identified in Wuhan, China. Early response from the Chinese government included quarantine of infected persons, isolation and total lockdown of Wuhan province to prevent further spread. With the spread of the disease across national borders and declaration of the disease as a global pandemic, there has been a robust response by the international community to contain this deadly virus and prevent its further spread worldwide. Africa is not left out of this rampaging pandemic with documented cases in over 40 countries and still rising. Although extensive studies have been carried out on the novel SARS-CoV-2 on its pathogenesis, mode of infection and virulence but much is still unknown. However, potentially infectious samples are received routinely in the medical laboratory for analysis. This technical note reviews good laboratory practice (GLP) and processes across the different specialities of Medical Laboratory practice that should minimize the risk of infection to laboratory staff especially in resource-limited settings.
ARTICLE Download: 32| View: 116| Comments: 1 | doi:10.20944/preprints202004.0102.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Medicinal plants; Mpro; 3CLpro; spike (S) glycoprotein; COVID-19; SARS-CoV-2
Online: 7 April 2020 (12:08:57 CEST)
Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.
HYPOTHESIS Download: 11| View: 14| Comments: 0 | doi:10.20944/preprints202004.0101.v1
Online: 7 April 2020 (12:07:22 CEST)
On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.
REVIEW Download: 3| View: 11| Comments: 0 | doi:10.20944/preprints202004.0100.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: ellagic acid; oral administration; bioavailability; microformulations; nanoformulations; solubility enhancement
Online: 7 April 2020 (12:02:54 CEST)
Ellagic acid, a polyphenolic compound present in fruits and berries, has recently been object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as chemopreventive agent has been debated because of its poor bioavailability associated to low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro-nanoparticles, inclusion complexes, self-emulsifying systems, polymorphs have been proposed. Here, we have listed an updated description of pursued micro/nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro/nano-sized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.
ARTICLE Download: 1| View: 5| Comments: 0 | doi:10.20944/preprints202004.0099.v1
Subject: Engineering, Control & Systems Engineering Keywords: Active Steering bogie; Steering angle; Steering Performance; Bogie angle; Lateral force; Derailment coefficient
Online: 7 April 2020 (11:58:49 CEST)
The steering performance according to the steering angle control was tested by using the active steering bogie developed to reduce excessive wheels and rail wear and noise generated when the railway vehicle run in a curved section. As a result of the test of increasing the steering angle in accordance with the target steering angle in the 300m radius of curvature, the bogie is gradually aligned in the radial steering position, and when the control is carried out to 100% of the target steering angle, the bogie angles of the front and rear bogies appeared almost the same. As the steering angle increased, wheel lateral force and derailment coefficient also decreased. Therefore, the validity of the radial steering position control method applied in this paper was confirmed experimentally. This test results will be used for future research on active steering bogie commercialization.
ARTICLE Download: 7| View: 11| Comments: 0 | doi:10.20944/preprints202004.0098.v1
Subject: Engineering, Mechanical Engineering Keywords: Compression Ratio (CR); CI Diesel Engine; Ethanol; Biodiesel; Performance; Combustion; Emissions and Emulsifier
Online: 7 April 2020 (11:56:15 CEST)
In the present scenario of increased industrialization and transportation in the world leads to increased consumption of fossil fuels which in turns leads to depletion of fossil fuels at a faster rate. Fossil fuels combustion is the dominant source for greenhouse gases and global warming. In view of energy crisis raised in 1970’s and environmental concern, many researches are directed towards search of alternative fuels which can replace consumption of fossil fuels as well as reduce pollution. In developing countries like India which is agriculture land the best alternative fuels are biodiesel and ethanol as they are produced from renewable feedstocks like sugarcane, corn etc. and they are also less hazardous to environment because of lower emission property. Ethanol blends results in significant reduction of emissions of hydrocarbon (HC), carbon monoxide (CO) and particulates matter but increase in nitrogen oxides (NOx). The main purpose of ethanol addition is to reduce the viscosity of biodiesel blends. This paper represents significance of Compression Ratio(CR) on performance, combustion and emission of single cylinder four stroke CI diesel engine by using various compression ratios such as 17.5:1, 18.5:1 and 19.5:1. Experimental research has been conducted with four types of ethanol blends, namely E10, E20, E30 and E40. Ethanol-biodiesel mixture mixed with 2% emulsifier 1% diethyl carbonate and 1% ethyl acetate to maintain similarity and to avoid phase separation. Ethanol subjected to high compression ratio has been used to increase brake thermal efficiency (BTE). The compression ratio has been increased to improve the combustion and performance of the diesel engine.
REVIEW Download: 25| View: 27| Comments: 0 | doi:10.20944/preprints202004.0097.v1
Subject: Life Sciences, Microbiology Keywords: convalescent plasma; serology; pathogen reduction technologies; pathogen inactivation; COVID-19; SARS-CoV2
Online: 7 April 2020 (11:47:15 CEST)
Convalescent blood product therapy has been introduced since early 1900s to treat emerging infectious disease based on the evidence that polyclonal neutralizing antibodies can reduce duration of viremia. Recent large outbreaks of viral diseases for whom effective antivirals or vaccines are still lacking has revamped the interest in convalescent plasma as life-saving treatments. This review summarizes historical settings of application, and surveys current technologies for collection, manufacturing, pathogen inactivation, and banking, with a focus on COVID-19.
ARTICLE Download: 2| View: 8| Comments: 0
Subject: Engineering, Electrical & Electronic Engineering Keywords: automated visual inspection; convolutional neural network; deep learning; pattern classification; semiconductor inspection; wafer map
Online: 7 April 2020 (11:30:38 CEST)
This article presents an automated vision-based algorithm for the die-scale inspection of wafer images captured using scanning acoustic tomography (SAT). This algorithm can find defective and abnormal die-scale patterns, and produce a wafer map to visualize the distribution of defects and anomalies on the wafer. The main procedures include standard template extraction, die detection through template matching, pattern candidate prediction through clustering, and pattern classification through deep learning. To conduct the template matching, we first introduce a two-step method to obtain a standard template from the original SAT image. Subsequently, a majority of the die patterns are detected through template matching. Thereafter, the columns and rows arranged from the detected dies are predicted using a clustering method; thus, an initial wafer map is produced. This map is composed of detected die patterns and predicted pattern candidates. In the final phase of the proposed algorithm, we implement a deep learning-based model to determine defective and abnormal patterns in the wafer map. The experimental results verified the effectiveness and efficiency of our proposed algorithm. In conclusion, the proposed method performs well in identifying defective and abnormal die patterns, and produces a wafer map that presents important information for solving wafer fabrication issues.
ARTICLE Download: 4| View: 9| Comments: 0 | doi:10.20944/preprints202004.0095.v1
Subject: Materials Science, Other Keywords: ceramic materials; composite structure; additive technologies; dynamic loading; transformation hardening
Online: 7 April 2020 (11:27:49 CEST)
This paper presents a physical and mathematical model that has been developed in the framework of the approach used in the computational mechanics of materials. The model is designed to enable the study of the patterns of deformation and fracture of ceramic composites with a transformation-hardened matrix that are obtained by additive technologies at the mesoscopic and macroscopic levels under intense dynamic loading. The influence of the loading rate on the formation of the fracture and energy dissipation fronts for composite materials, based on the Al2O3 20%ZrO2 system, is shown. Nonlinear effects under intense dynamic loading in the considered composites are associated with the processes of self-organization of structural fragments at the mesoscopic level, as well as the occurrence of martensitic phase transformations in matrix volumes adjacent to the strengthening particles.
HYPOTHESIS Download: 28| View: 21| Comments: 0 | doi:10.20944/preprints202004.0094.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; zinc; zn; zinc-deficiency; cytokine storm
Online: 7 April 2020 (11:22:53 CEST)
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic for which there is no established treatment available yet, has caused more than 68,000 deaths so far. Following the SARS-CoV outbreak in 2003, an Italian group described a hypothesis about the efficacy of two old drugs: Chloroquine (CQ) and Hydroxychloroquine (HCQ), against SARS-CoV and its future emergents. Later, this hypothesis was shown to be relevant in-vitro. Due to the high genetic similarity of SARS-CoV-2 and SARS-CoV, the hypothesis introduced by Savarino et al. and the further supportive in-vitro evidence served a rational ground for three different Chinese groups to test the efficacy of CQ or HCQ against SARS-CoV-2 in-vitro. These studies showed promising in-vitro efficacy of CQ and HCQ against SARS-CoV-2. Unfortunately, in the absence of sufficient clinical data on the (in)efficacy of CQ and HCQ in SARS-CoV-2 patients, the compassionate and off-label use of these medications is becoming politicized. Herein, we underline some critical features of the CQ/HCQ mechanism of action concerning SARS-CoV-2. Moreover, we put forward a hypothesis based on three lines of evidence on a probable link between zinc-deficiency/zinc correction and response to CQ/HCQ- and possibly other SARS-CoV-2 treatments.
COMMUNICATION Download: 21| View: 41| Comments: 0 | doi:10.20944/preprints202004.0093.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS-CoV-2; virus, bioaerosol; social distancing; aerodynamic size; infection
Online: 7 April 2020 (11:20:42 CEST)
The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine and antidote, resulted in the decision of multiple governments to force measurements of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 6.0 ft (1.8 m) from persons with COVID-19. The eventual exposure to the bioaerosol can result in the deposition o the pathogen in the respiratory track of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic particle size in carrying RNA copies of the novel coronavirus. A COVID-19 carrier person talking, sneezing, or coughing at distance of 1.8 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.
ARTICLE Download: 5| View: 11| Comments: 0 | doi:10.20944/preprints202004.0092.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Acute coronary syndrome; inflammation; neutrophil; outcome
Online: 7 April 2020 (11:18:03 CEST)
Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.
REVIEW Download: 43| View: 148| Comments: 0 | doi:10.20944/preprints202004.0091.v1
Subject: Life Sciences, Virology Keywords: Coronavirus; Pneumonia; COVID-19; Virus; Flu; Vaccine; Epidemic; Pandemic
Online: 7 April 2020 (11:15:55 CEST)
The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.
HYPOTHESIS Download: 26| View: 32| Comments: 0 | doi:10.20944/preprints202004.0090.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19: hydroxychloroquine aerosol; pharmacotherapy; prevention; SARS-CoV-2
Online: 7 April 2020 (11:11:09 CEST)
Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.
SHORT NOTE Download: 10| View: 15| Comments: 0 | doi:10.20944/preprints202004.0089.v1
Subject: Life Sciences, Other Keywords: Sars-CoV-2; Homology modelling; Envelope Membrane glycoprotein; Bat; Pangolin; Sars-CoV
Online: 7 April 2020 (11:09:23 CEST)
The Coronavirus disease (COVID-19) is a new viral infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) that was initially reported in city of Wuhan, China and afterwards spread globally. Genomic analyses revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) Pangolin and Bat coronavirus specific isolates. In this study we focused on two proteins of Sars-CoV-2 surface: Envelope protein and Membrane protein. Sequences from Sars-CoV-2 isolates and other closely related virus were collected from the GenBank through TBlastN searches. The retrieved sequences were multiply aligned with MAFFT. The Envelope protein is identical to the counterparts from Pangolin CoV MP798 isolate and Bat CoV isolates CoVZXC21, CoVZC45 and RaTG13. However, a substitution at position 69 where an Arg replace for Glu, and a deletion in position 70 corresponding to Gly or Cys in other Envelope proteins were found. The Membrane glycoprotein appears more variable with respect to the SARS CoV proteins than the Envelope: a heterogeneity at the N-terminal position, exposed to the virus surface, was found between Pangolin CoV MP798 isolate and Bat CoV isolates CoVZXC21, CoVZC45 and RaTG13. Mutations observed on Envelope protein are drastic and may have significant implications for conformational properties and possibly for protein-protein interactions. Mutations on Membrane protein may also be relevant because this protein cooperates with the Spike during the cell attachment and entry. Therefore, these mutations may influence interaction with host cells. The mutations that have been detected in these comparative studies may reflect functional peculiarities of the Sars-CoV-2 virus and may help explaining the epizootic origin the COVID-19 epidemic.
ARTICLE Download: 4| View: 10| Comments: 0 | doi:10.20944/preprints202004.0088.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: Enhance heat transfer; Nanofluids; CNTs; Fractional derivatives; Laplace transform
Online: 7 April 2020 (11:04:32 CEST)
Nanofluids are a novel class of heat transfer fluid that plays a vital role in industries. In mathematical investigations, these fluids are modeled in terms of traditional integer-order partial differential equations (PDEs). It is recognized that traditional PDEs cannot decode the complex behavior of physical flow parameters and memory effects. Therefore, this article intends to study the mixed convection heat transfer in nanofluid over an inclined vertical plate via fractional derivatives approach. The problem in hand is modeled in connection with Atangana-Baleanu fractional derivatives without singular and local kernel having strong memory. The human blood is considered as base fluid dispersing carbon nanotube (CNTs) (single-wall carbon nanotubes (SWCNTs) and multi-wall carbon nanotubes(MWCNTs )) into it to form blood-CNTs nanofluid. The nanofluids are considered to flow in a saturated porous medium under the influence of an applied magnetic field. The exact analytical expressions for velocity and temperature profiles are acquired using the Laplace transform technique and plotted in various graphs. The empirical results indicate that the memory effect decreases with increasing fractional parameters in the case of both temperature and velocity profiles. Moreover, the temperature profile is higher for blood-SWCNTs by reason of higher thermal conductivity whereas, this trend is opposite in case of velocity profile due densities difference.
REVIEW Download: 27| View: 73| Comments: 0 | doi:10.20944/preprints202004.0087.v1
Online: 7 April 2020 (11:02:13 CEST)
Efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), have just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are known at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.
ARTICLE Download: 5| View: 9| Comments: 0 | doi:10.20944/preprints202004.0085.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: image denoising; multiplicative noise; speckle noise; total variation(TV) filter; multiquadric radial basis functions (MQ-RBF); restoration equation; meshless scheme
Online: 7 April 2020 (11:01:03 CEST)
This article introduces a fast meshless numerical algorithm to solve nonlinear partial di?erential equations (PDE) through Radial Basis Functions (RBFs) approximation connected with the Total Variation (TV)-based minimization functional and to show its application to image denoising containing multiplicative noise. These features in the proposed algorithm not only to remove the noise from the images and preserve the edges but also to reduce the staircase effect extensively from images that cause the image to look blocky. It is worth mentioning that the proposed approach can be easily employed for nonlinear problems due to the lack of dependence on a mesh or integration procedure. The numerical experiments and comparative examples illustrate the effectiveness of the proposed algorithm regarding the robustness and visual improvement as well as peak-signal-to-noise ratio (PSNR), signal-to-noise ratio (SNR), and mean structural similarity index (MSSIM) compared to the recent traditional TV-based methods.
ARTICLE Download: 6| View: 19| Comments: 0
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: 2019 novel coronavirus; COVID-19; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; GAN
Online: 7 April 2020 (10:59:04 CEST)
The coronavirus (covid-19) pandemic is putting healthcare systems across the world under unprecedented and increasing pressure according to the World Health Organization (WHO). With the advances in computer algorithms and especially Artificial Intelligence, the detection of this type of virus in the early stages will help in fast recovery and help in releasing the pressure off healthcare systems. In this paper, a GAN with deep transfer learning for coronavirus detection in chest x-ray images is presented. The lack of benchmark datasets for covid-19 especially in chest x-rays images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the writing of this research and use the GAN network to generate more images to help in the detection of the virus from the available x-rays images with the highest accuracy possible. The dataset used in this research was collected from different sources and it is available for researchers to download and use it. The number of images in the collected dataset is 307 images for four different types of classes. The classes are the covid-19, normal, pneumonia bacterial, and pneumonia virus. The dataset is divided into 90% for the GAN and the training and the validation phase, while 10% used in the testing phase. The GAN helps in generating more images from the original dataset to be 30 times larger than the originally collected dataset. The GAN also help in overcoming the overfitting problem and made the proposed model more robust. Three deep transfer models are selected in this research for investigation. The models are the Alexnet, Googlenet, and Restnet18. Those models are selected based on their small number of layers on their architectures, which will reflect in reducing the complexity of the models and the consumed memory and time. Using a combination of GAN and deep transfer models prove it is efficiency according to validation, testing accuracy, and performance measurements such as precision, recall, and F1 score. Three case scenarios are tested through the paper, the first scenario which includes 4 classes from the dataset, while the second scenario includes 3 classes and the third scenario includes 2 classes. All the scenarios include the covid-19 class as it is the main target of this research to be detected. In the first scenario, the Googlenet is selected to be the main deep transfer model as it achieves 80.6% in testing accuracy. In the second scenario, the Alexnet is selected to be the main deep transfer model as it achieves 85.2% in testing accuracy, while in the third scenario which includes 2 classes(covid-19, and normal), Googlenet is selected to be the main deep transfer model as it achieves 100% in testing accuracy and 99.9% in the validation accuracy. All the performance measurement strengthen the obtained results through the research. Finally, this research may be considered one of the first trails to use GAN and deep transfer models together to help in detecting coronaviruses (covid-19) within the absence of a benchmark dataset around the world, especially in x-rays chest images.
ARTICLE Download: 10| View: 65| Comments: 0 | doi:10.20944/preprints202004.0084.v1
Subject: Chemistry, Medicinal Chemistry Keywords: in silico repositioning; dual inhibitor; Covid-19; 3CLpro; PLpro; remdesivir
Online: 7 April 2020 (10:44:11 CEST)
Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.
REVIEW Download: 5| View: 10| Comments: 0 | doi:10.20944/preprints202004.0083.v1
Subject: Biology, Plant Sciences Keywords: drought-tolerance characteristics; maize breeding; maize drought tolerance; molecular markers; phenotype; screening of drought-tolerant plants
Online: 7 April 2020 (10:28:30 CEST)
Drought is among the most important abiotic stressors influencing food-crop production worldwide. Currently, drought-tolerant maize materials are rarely used for actual breeding because corn production primarily focuses on heterosis to generate desired varieties. In this article, we reviewed current work on assessing maize drought tolerance. We suggested that the development of enhanced screening techniques must clearly consider the connection between theory and application. We strongly recommend that agricultural scientists focus on translating the results of laboratory experiments into practical methods for improving crop productivity.
REVIEW Download: 29| View: 32| Comments: 0 | doi:10.20944/preprints202004.0082.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID-19; global pandemic; global health emergency; SARS-CoV-2
Online: 7 April 2020 (10:08:47 CEST)
The 2019 novel coronavirus (previously 2019-nCoV) or coronavirus infectious disease 2019 (COVID-19) outbreak has been summarized as on March 29, 2020. COVID-19 is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SERS-CoV-2). The disease was first seen during an outbreak in Wuhan, China and continuous spreading from human to human around the sphere. The disease is uncontrolled and increasing the death toll through. The world is facing a global challenge to protect human lives caused by coronavirus outbreak. The number of infected patients is increasing day by day due to COVID-19 as a pandemic. The world health organization (WHO) has declared global public health emergency on January 30, 2020. The disease has been spread around 201 countries with total confirmed cases 634835 and death cases 29891 as on March 29, 2020. The goal of this review to summaries and update the clinical/medical features and suggestions for diagnosis of the COVID-19 as a pandemic. The discussion of the various therapeutic algorithms, risk, prevention and control based on the latest reports has been provided.
ARTICLE Download: 4| View: 13| Comments: 0 | doi:10.20944/preprints202004.0081.v1
Subject: Engineering, Other Keywords: physiological traits; element contents; drought stress; nano fertilizers
Online: 7 April 2020 (09:56:05 CEST)
Nano fertilizers offer benefits in nutrition management through their strong potential to increase nutrient use efficiency. Nutrients, either applied alone or in combination, are bound to nano-dimensional adsorbents, which release nutrients very slowly as compared to conventional fertilizers. Traditional fertilizers are not only costly for the producer, but may be harmful to humans and the environment. Furthermore, nanofertilizers may also be used for enhancing abiotic stress tolerance. This study was performed to evaluation of nano chelated nitrogen and urea fertilizers on physiological characteristic of wheat under drought stress condition. Experiments were carried out in two locations in Fars province, Iran. Experimental design was performed as split-split plot in RCBD design. The first factor included irrigation treatments (normal and withholding irrigation at flowering stage), sub factor was nitrogen treatment (0, 37, 74 and 110 kg.ha-1) in the form of Urea fertilizer, and sub-sub factor was nitrogen (0, 14, 27 and 41 kg.ha-1) in the form of nano chelated nitrogen fertilizer. Studied traits were RWC, Ion Leakage, Protein, Phosphorus and Potassium content, Remobilization and photosynthesis rate. According to analysis of variances, stress, nitrogen (urea) and nano chelated nitrogen had significant effects on all studied traits. Mean comparisons showed that drought stress led to 13% reduction in RWC, 21% Ion Leakage, 26% Protein, 13% Phosphorus and 26% Potassium content, 22% Remobilization and 69% photosynthesis rate compared to normal irrigation In conclusion Application of 41 kg.ha-1 nano chelated nitrogen fertilizer in comparison with urea led to increase 4% in Rwc, 3% Ion leakage, 52% protein, 26% phosphor, 6% potassium, 6% Remobilization and 21% photosynthesis rate compared to control, respectively.
REVIEW Download: 6| View: 14| Comments: 0 | doi:10.20944/preprints202004.0080.v1
Subject: Life Sciences, Biotechnology Keywords: cancer-related viruses; CRISPR-Cas diagnostic tools; DETECTR; infectious disease; SHERLOCKv2
Online: 7 April 2020 (09:43:22 CEST)
Sensitive and precise nucleic acid detection is critical for clinical diagnostics and biotechnological advancements. Diagnostic in infectious disease field is very unique from diagnosing any other disease, that is time is of the essence; in outbreaks people die even with each passing hour in some cases, if the correct diagnosis wasn't make; for example Zika in particularly is a very challenging virus to diagnose, because it's in very few numbers of copies in the infected person, so it need high sensitive diagnostic approach to spot it, In particular, the advanced tools SHERLOCKv2 and DETECTR, give almost an immediate detection of attomolar amounts of pathogenic nucleic acids with specificity similar to that of PCR but with slight technical settings and that will guide the correct intervention for the patient. SHERLOCKv2 and DETECTR technologies are game changers for our ability to identify infectious disease and rapid detection of tumor DNA or cancer-related viruses with ultra-sensitive tests that don’t require a lot of complicated processing to go through. In this paper, we will review cutting-edge infectious disease diagnosis by CRISPR-Cas systems.
ARTICLE Download: 24| View: 63| Comments: 0 | doi:10.20944/preprints202004.0079.v1
Subject: Chemistry, Medicinal Chemistry Keywords: COVID-19; Nigella Sativa; 6LU7; 2GTB; molecular docking; MOE software
Online: 7 April 2020 (08:58:42 CEST)
The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of Nigella Sativa against coronavirus infection.
ARTICLE Download: 7| View: 19| Comments: 1 | doi:10.20944/preprints201911.0004.v2
Subject: Physical Sciences, Particle & Field Physics Keywords: monopoles; tachyons; elliptic orbits; photographic emulsion; detection; Coulomb’s law; Kepler orbits; hydrogen
Online: 7 April 2020 (04:18:26 CEST)
Based on detection of elliptic particle tracks, $\simeq 137^2 n^2$ bigger than Bohr-Sommerfeld electron orbits, indicating the possible detection of superluminal electrons masquerading as magnetic monopoles, a new structure emerges leading to: (i) a new set of seven elementary lengths; (ii) replacement of the usual motion (Lorentz) transformations by scale transformations between $v^2<c^2$ and $v^2>c^2$ frames; (iii) equivalence of charge between $v^2<c^2$ and $v^2>c^2$ frames based on the Dirac-Schwinger quantization condition; (iv) a relativistic foundation for the Dirac-Schwinger quantization condition; (v) a possible cause of charge quantization; and (vi) the prospect of symmetry in Maxwell's equations. If the elliptic particle tracks are viewed as a magnification of electron orbits, the effect is suggestive of a spacetime distortion such as those predicted in general relativistic theories.
ARTICLE Download: 25| View: 44| Comments: 0 | doi:10.20944/preprints202004.0078.v1
Subject: Behavioral Sciences, Social Psychology Keywords: COVID-19; R0; WHO; social distancing; H1N1; H2N2; influenza
Online: 7 April 2020 (02:48:13 CEST)
The current outbreak of the novel coronavirus also known as COVID-19 was declared as a public health emergency by the WHO where over a million people have been affected by the disease with over 50000 deaths till date. Social distancing is a method to minimize crowd interactions and prevent the spread of disease within groups of people. This is a common practice which has been carried out over generations to minimize the spread of virus by limiting its reproduction rate (R0) among communities. The article focuses on how social distancing has been used to deal previous pandemics globally and the issues that needs to be addressed to tackle the COVID-19 threat.
REVIEW Download: 55| View: 38| Comments: 0 | doi:10.20944/preprints202004.0077.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; native American Indian; treatment; ACE2 receptor; pathophysiology; virulence
Online: 7 April 2020 (02:40:24 CEST)
Background: On Dec 19, 2019 it was reported by the public health department of China 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 or MERSs viruses and on March 11, 2020 the World Health Department (WHO) declared world -wide pandemic. Understanding the pathophysiology of virulence of the COVID-19 virus is absolutely necessary in understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance to any current or future treatment protocols. Methodology: A PubMed search was performed 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 COVID-19 virus is much more virulent than either the SARs or MERs 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 do not vary among different ethnic groups but do in 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.
BRIEF REPORT Download: 10| View: 26| Comments: 0 | doi:10.20944/preprints202004.0076.v1
Online: 7 April 2020 (02:27:40 CEST)
Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21st century. Here, the host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a shared pool of variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants were of the utmost importance to the viral entry and infection. In the absence of gender bias for the gene expression profiles, the hemizygous rare variants of ACE2 describe the observed higher mortality rate in males. Finally, a personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.
REVIEW Download: 47| View: 94| Comments: 0 | doi:10.20944/preprints202004.0075.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; immunotherapeutics; therapeutics; vaccines
Online: 7 April 2020 (02:01:34 CEST)
A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.
REVIEW Download: 7| View: 14| Comments: 1
Subject: Biology, Other Keywords: stress granules; G3BP1; G3BP2; Caprin-1; USP10; TIA1; TIAR; cancer prognosis; biomarker; metastasis; resistance; cell death; pro-survival properties
Online: 7 April 2020 (01:56:12 CEST)
Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.
REVIEW Download: 9| View: 18| Comments: 0 | doi:10.20944/preprints202004.0074.v1
Subject: Keywords: breast tumor; mammary neoplasm; breast carcinoma; meta-analysis; population at risk
Online: 7 April 2020 (01:22:38 CEST)
To systematically investigate the epidemiology of breast cancer risk factors in Iran, we performed a systematic search via PubMed, Scopus, Web of Science and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models.Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), HRT (OR: 5.48, 95%CI 0.84-1.74), ER positive (OR: 1.87, 95%CI 1.41-2.33), PR positive (OR: 1.84, 95%CI 1.38-2.29), stress condition (OR: 2.67, 95%CI 1.84-3.50), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13 to 24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46).This study suggest that factors such as family history, HRT, ER and PR positive status, stress condition, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.
ARTICLE Download: 18| View: 29| Comments: 0 | doi:10.20944/preprints202004.0073.v1
Subject: Mathematics & Computer Science, Numerical Analysis & Optimization Keywords: SARS-CoV-2; COVID-19; SEIR modeling; Italy; stochastic modeling; swarm intelligence
Online: 7 April 2020 (01:13:15 CEST)
We applied a generalized SEIR epidemiological model to the recent SARS-CoV-2 outbreak in the world, with a focus on Italy and its Lombardia, Piemonte, and Veneto regions. We focus on the application of a stochastic approach in fitting the model numerous parameters, to improve the reliability of predictions in the medium term (30 days). We analyze the official data and the predicted evolution of the epidemic in the Italian regions, and we compare their results also with data and predictions of Spain and South Korea. We discuss the effectiveness of policies taken by different regions and countries and how they have an impact on past and future infection scenarios.
CASE REPORT Download: 24| View: 46| Comments: 1
Subject: Life Sciences, Virology Keywords: COVID-19; coronavirus; fulminant myocarditis; infection; echocardiography.
Online: 7 April 2020 (01:03:22 CEST)
Background: Coronavirus Disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/ml. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.
ARTICLE Download: 18| View: 15| Comments: 0 | doi:10.20944/preprints202004.0072.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Bacillus pumilus HY1; solid-state fermentation; cheonggukjang; surfactin; mass spectrum; anticancer effect
Online: 7 April 2020 (00:54:39 CEST)
The cyclic lipopeptide produced from Bacillus pumilus strain HY1 was isolated from Korean soybean sauce. The chemical structures of the surfactin isomers were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). The five potential surfactin isoforms were detected with protonated masses of m/z 994.7, 1,008.7, 1022.7, 1036.7, and 1,050.7 and different structures in combination with Na+, K+, and Ca2+ ions. ESI-MS/MS analysis revealed that the isolated surfactin possessed the precise amino acid sequence LLVDLL and hydroxyl fatty acids with 12 to 16 carbons. The surfactin content during cheonggukjang fermentation increased from 0.3 to 51.2 mg/kg over 60 h of fermentation. The surfactin extraction of cheonggukjang inhibited the growth of two cancer cell lines. The growth of both MCF-7 and Caco-2 cells was strongly inhibited with 100 μg/μL surfactin. These results suggest that surfactins produced from strain HY1 have anticancer properties.
Mon, 6 April 2020
REVIEW Download: 56| View: 91| Comments: 0 | doi:10.20944/preprints202004.0071.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS CoV; macrophage activation syndrome; cytokine storm; immunology
Online: 6 April 2020 (16:22:42 CEST)
Introduction: The COVID-19 pandemic is a global crisis, the number of cases and deaths are on a steep incline. This article reviews the possible immunological mechanisms which underlie the disease pathogenesis by looking at the behaviour of previous coronaviruses not only in humans but also other mammals which possibly act as reservoir hosts. Observations: A key aspect of this coronavirus as well as the previous SARS CoV seems to be the importance of host immune response in the pathology and clinical severity of illness caused by them. A hyperactive innate immune state in combination with an exhausted adaptive immune response are possible determinants of severe illness. Conclusion: There is a possibility that the current SARS CoV 2 has immune evasive tactics similar to SARS CoV in its repertoire, since they share a 76% homology. These might have been learnt behaviour from long periods of persistence in their reservoir hosts and they may be the reason behind the dysregulated immune response evoked in humans. That in turn is highly likely to be one of the factors which govern disease severity. With this in mind we want to bring the medical community’s attention to a ‘hit early, hit hard’ intervention as a possible strategy to modify the course of the disease and bring down the numbers of severe sufferers.
ARTICLE Download: 14| View: 43| Comments: 0 | doi:10.20944/preprints202004.0070.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: doxycycline; assay; dosage uniformity; hardness; friability; dissolution profile
Online: 6 April 2020 (15:56:54 CEST)
Persistent post market quality evaluation helps produce clear information on the current quality status of the different brands of a given drug and hence introduces biopharmaceutically and therapeutically equivalent list of the products to the prescribers and users of it. This in turn facilitates access to essential medicines by breaking the high cost barrier imposed by few expensive brands of the product. This study was aimed at determining the quality and evaluating equivalence of doxycycline hyclate capsules and tablets in Jimma, Ethiopia. Ten brands of doxycycline hyclate capsules and tablets were tested for physic-chemical parameters. All investigated brands of doxycycline complied with the USP for dosage unifor¬mity, assay of active ingredient and single-point dissolution tests. One brand, D09 failed both hardness and friabilty tests. Comparisons of dissolution profiles applying fit factors confirmed that only brands D04, D06 and D07 had similarity with innovator. Ratio test approaches also showed significant variability existence between test products and comparators. This may question the product’s being categorized as a <biowaiver> to mean in-vitro dissolution evaluation suffices its market approval. This work, however, found equivalence problems between ‘comparators’ and interchangeability issues among doxycycline different brands already distributed in the market.
REVIEW Download: 33| View: 66| Comments: 0 | doi:10.20944/preprints202004.0069.v1
Subject: Earth Sciences, Environmental Sciences Keywords: coronavirus; SARS-CoV-2; COVID-19; respiratory diseases; air pollution
Online: 6 April 2020 (15:48:46 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.
ARTICLE Download: 41| View: 160| Comments: 0 | doi:10.20944/preprints202004.0068.v1
Subject: Life Sciences, Biotechnology Keywords: coronavirus; COVID-19; hACE-2; MPro; multi-target-directed ligand; protease inhibito; RdRp; SARS-CoV-2 virus
Online: 6 April 2020 (15:35:33 CEST)
The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Coronaviridae family. The disease has infected more than 1 million individuals worldwide with a mortality rate ranging from 5 to 10 %. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was also corroborated with the structural comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of the custom-made library of ~ 7000 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. It has been observed that natural molecules like d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin, Phyllaemblicin B and other several molecules show strong binding with the SARS-CoV-2 MPro. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.
ARTICLE Download: 10| View: 31| Comments: 0 | doi:10.20944/preprints202004.0067.v1
Subject: Engineering, Energy & Fuel Technology Keywords: wind power; wind energy; coastal regions; statistical distributions; wind turbine capacity factor
Online: 6 April 2020 (15:29:16 CEST)
Wind power output is highly dependent on the wind speed at the selected site, therefore wind-speed distribution modeling is the most important step in the assessment of wind energy potential. This study aims at accurate evaluation of onshore wind energy potential in seven coastal cities in the south of Iran. Six Probability Distribution Functions (PDFs) were examined over representative stations. It has been deduced that the Weibull function, which was the most used PDF in similar studies, was only applicable to one station. Here, Gamma offered the best fit for three stations and for the other ones, Generalized Extreme Value (GEV) performed better. Considering the ranking of six examined PDFs and the simplicity of Gamma, it was identified as the effective function in the southern coasts of Iran bearing in mind the geographic distribution of stations. Besides, six turbine power curve functions were contributed to investigate the capacity factor. That was very important, as using only one function could cause under- or over-estimation. Then, stations were classified based on the National Renewable Energy Laboratory system. Last but not least, examining a range of wind turbines enabled scholars to extend this study into the practice and prioritize development of stations considering budget limits.
ARTICLE Download: 37| View: 95| Comments: 0 | doi:10.20944/preprints202004.0066.v1
Subject: Life Sciences, Biotechnology Keywords: mitigation strategy; COVID-19; epidemics; health policy; public and global health; demographics; social distancing
Online: 6 April 2020 (15:20:55 CEST)
COVID-19 severity is heterogeneously distributed over age strata, but current mitigation strategies are homogeneously applied to all population. Social-distancing and stay-home are effective conservative approaches but lack economical sustainability on long term. Conversely, herd-immunity is a nonrestrictive strategy which can cost remarkable number of human lives and can melt the healthcare system down.Here I propose an Age Adaptive Social Distancing (AASD) engineering strategy to mitigate COVID-19 outbreak. AASD is based on the scientific evidence that the fatality rate grows nonlinearly with age, hence also the containing strategy should adapt nonlinearly. Essentially, AASD suggests that ‘silent spreaders’ (age 0-39) should avoid/minimize direct and indirect contacts with individuals in ‘dangerous zone’ (age 40+). The rationale is: 0-19 should follow parents strategy, healthy 20-39 (low fatality rate) might conduct screened life under active surveillance, to sustain economy and acquire rational immunity; 40-59 should respect social distancing (waiting a therapy); 60+ should stay at home (waiting a vaccine). This might save human lives, reduce healthcare demand and improve economical sustainability. The final take-home message is that future studies should design precision and personalized strategies for specific contagious diseases that integrate different social constrains, active surveillance and contact tracing.
REVIEW Download: 140| View: 313| Comments: 0 | doi:10.20944/preprints202004.0065.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; case fatality rate; Italy; testing; health care system; demographics; comorbidites; epidemiological trends
Online: 6 April 2020 (15:17:12 CEST)
There is much discussion among clinicians, epidemiologists, and public health experts about why case fatality rate from COVID-19 in Italy (at 12.1% as of April 2, 2020, versus a global case fatality rate of 5.2%) is considerably higher than estimates from other countries (especially China, South Korea, and Germany). In this article, we propose several potential explanations for these differences. We suggest that Italy’s overall and relative case fatality rate, as reported by public health authorities, is likely to be inflated by such factors as heterogeneous reporting of coronavirus-related fatalities across countries and the iceberg effect of under-testing, yielding a distorted view of the global severity of the COVID-19 pandemic. We also acknowledge that deaths from COVID-19 in Italy are still likely to be higher than in other equally affected nations due to its unique demographic and socio-economic profile. Lastly, we discuss the important role of the stress imparted by the epidemic on the Italian healthcare system, which weakened its capacity to adequately respond to the sudden influx of COVID-19 patients in the most affected areas of the country, especially in the Lombardy region.
ARTICLE Download: 5| View: 15| Comments: 0 | doi:10.20944/preprints202004.0064.v1
Subject: Life Sciences, Virology Keywords: erythroparvovirus, tetraparvovirus, protein sequence analyses, overlapping genes, overlapping reading frames VP1, capsid
Online: 6 April 2020 (14:20:35 CEST)
30 years ago, researchers noticed that the capsid (VP1) gene of B19 parvovirus might encode a second protein, called "X", in an overlapping reading frame. Since then, experimental approaches failed to detect it. In contrast, sequence analyses can reliably predict whether a protein is expressed from an overlapping frame, provided that it is beneficial to the virus and thus under selection pressure. We used a dedicated software, Synplot2, to identify regions of VP1 likely to encode functional proteins in overlapping frames. Synplot2 detected the X open reading frame and confirmed it is under highly significant selection pressure. We discovered that the X protein is homologous to the ARF1 protein of human parvovirus 4, another suspected protein encoded in a frame overlapping VP1. These findings provide compelling evidence that the X protein must be expressed and functional. We predict that it contains a predicted transmembrane region. We found that the X frame contains a potential AUG start codon in parvovirus B19 and in all related species. Yet no currently known viral transcript has the potential to encode the X protein in a monocistronic fashion. Therefore, the X protein is probably expressed either from an unmapped monocistronic mRNA, or translated by a non-canonical mechanism from the VP1 mRNA or from a short transcript, R3, which has no currently known function. Finally, Synplot2 also detected proteins likely to be expressed from a frame overlapping VP1 in species distantly related to parvovirus B19: porcine parvovirus 2 and bovine parvovirus 3.
ARTICLE Download: 66| View: 129| Comments: 0 | doi:10.20944/preprints202004.0063.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2; COVID-19; Pandemic geographical distribution; Epidemic forecasting; Weather conditions; Climatic zones.
Online: 6 April 2020 (14:11:52 CEST)
This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic – also known as COronaVIrus Disease 19 (COVID-19) – could have been favored by specific weather conditions. It was found that the 2020 winter weather in the region of Wuhan (Hubei, Central China) – where the virus first broke out in December and spread widely from January to February 2020 – was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic has been very severe from February to March. The similarity suggests that this pandemic worsens under weather temperatures between 4°C and 11°C. Based on this result, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From January to March, this isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, coinciding with the geographic regions most affected by the pandemic from January to March. It is predicted that next spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year. Google-Earth-Pro interactive-maps are provided as supplements.
COMMUNICATION Download: 23| View: 45| Comments: 1 | doi:10.20944/preprints202003.0184.v2
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; diagnosis; antibody; serology; screening
Online: 6 April 2020 (14:09:34 CEST)
To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.
COMMUNICATION Download: 80| View: 203| Comments: 0 | doi:10.20944/preprints202004.0062.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; FDA approved drugs; High Throughput Virtual Screening; Sincalide; Pentagastrin.
Online: 6 April 2020 (14:09:04 CEST)
In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.
REVIEW Download: 31| View: 24| Comments: 0 | doi:10.20944/preprints202004.0061.v1
Subject: Biology, Ecology Keywords: Forests; Emerging infectious diseases; Disease transmission; Human pathogen; Environmental impacts
Online: 6 April 2020 (14:06:44 CEST)
Deforestation and associated changing landscapes are major components of environmental changes, with important implications for ecosystem functioning and biodiversity conservation. Tropical forests are hot spots of biodiversity and provide multiple goods and ecosystem services which benefit people in many ways Forest also play an important role in health-related legends, myths, and fairy tales from all over the world, and are important sources of new potential emerging microbial threats to human. Although plausibly numerous abundant microbial forms with a forest origin may exist, our systematic literature review shows that forest-derived infection studies are relatively unexplored, and both taxonomically and geographically biased. Since biodiversity has been associated with emergence of novel infectious diseases at macro-scale, we describe the main biogeographical patterns in the emerging infection-biodiversity-forest loss nexus. Then, we illustrate four fine-scale case studies to decipher the underlying processes of increased infection risk in changing forest clearing landscapes. Finally, we identify scientific challenges and regional management measures required to mitigate these important new emerging threats.
HYPOTHESIS Download: 45| View: 128| Comments: 0 | doi:10.20944/preprints202004.0060.v1
Subject: Life Sciences, Immunology Keywords: COVID-19; coronavirus; cytokine storm; immunity; ADE; cross-reactive antibody; rapamycin; mTOR inhibotors
Online: 6 April 2020 (14:03:00 CEST)
COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.
ARTICLE Download: 19| View: 32| Comments: 1 | doi:10.20944/preprints202004.0034.v2
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: Shannon entropy; Hurst exponent; Amino acid; Frequency distribution; \& SARS-CoV2
Online: 6 April 2020 (14:00:15 CEST)
The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.
ARTICLE Download: 7| View: 18| Comments: 0 | doi:10.20944/preprints202004.0059.v1
Subject: Engineering, Civil Engineering Keywords: ground tire rubber (GTR); anti stripping agents (ASA); stone matrix asphalt (SMA); waste polyethylene terephthalate (PET); rutting; fatigue
Online: 6 April 2020 (13:50:00 CEST)
The current study assessed the influence of Anti Stripping Agents (ASA), Ground Tire Rubber (GTR) and waste polyethylene terephthalate (PET) on performance behavior of binder and Stone Matrix Asphalt (SMA) mixtures. Through this paper, the 85/100 penetration grade bitumen was utilized as original bitumen. Also, three liquid ASA’s (ASA (A), ASA (B), ASA (C)) were used as a mixture modifier. For this purpose, softening point, penetration, rotational viscosity, Dynamic Shear Rheometer, Multi Stress Creep Recovery (MSCR) and Linear Amplitude Sweep (LAS) tests were implemented to investigate the rheological properties of modified bitumen. For evaluating the behavior of modified mixtures several tests such as; Resilient Modulus, Tensile Strength, dynamic creep, wheel track and four-point beam fatigue tests were implemented. Based on MSCR test results, utilization of mentioned polymers enhanced the elasticity of bitumens and therefore the permanent deformation resistance of binders increases. Also by the addition of PET percentage, the rutting resistance improves. Results indicated that utilization of ASAs, PET and Crumb Rubber (CR) enhance the Resilient Modulus (Mr), Indirect Tensile Strength (ITS), rutting resistance, fatigue life and Fracture Energy (FE) of asphalt mixtures. Also based on results, modification of binder by PET/CR with a ratio of 50%/50% and ASA (B) have the highest fatigue life which indicates that this mixture has highest resistance against fatigue cracking.
ARTICLE Download: 1408| View: 9945| Comments: 0 | doi:10.20944/preprints202004.0058.v1
Subject: Medicine & Pharmacology, Other Keywords: coronavirus disease 2019 (COVID-19); school closure; time series analysis; Japan
Online: 6 April 2020 (13:11:12 CEST)
Background: Coronavirus disease 2019 (COVID-19) pandemic are causing significant damages to many nations. For mitigating its risk, Japan’s Prime Minister called on all elementary, junior high and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing disease burden has not been investigated. Methods: We used daily data on the report of COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time series analysis were conducted using Bayesian method. Local linear trend models with interventional effect were constructed for number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of intervention start to appear 9 days after the school closure; i.e., on March 9. Results: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, mean coefficient α for effectiveness of the measure was calculated to be 0.08 (95% credible interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with rather wide credible interval. Sensitivity analyses using different dates also showed similar results. Conclusions: School closure carried out in Japan did not show the effectiveness to mitigate the transmission of novel coronavirus infection.
ARTICLE Download: 12| View: 18| Comments: 2 | doi:10.20944/preprints201908.0037.v3
Subject: Mathematics & Computer Science, General & Theoretical Computer Science Keywords: complexity classes; completeness; polynomial time; reduction; logarithmic space; one-way
Online: 6 April 2020 (12:57:55 CEST)
P versus NP is considered as one of the most important open problems in computer science. This consists in knowing the answer of the following question: Is P equal to NP? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the P versus NP problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity classes are L and NL. Whether L = NL is another fundamental question that it is as important as it is unresolved. We demonstrate that every problem in NP could be NL-reduced to another problem in L. In this way, we prove that every problem in NP is in NL with L Oracle. Moreover, we show the complexity class NP is equal to NL, since it is well-known that the logarithmic space oracle hierarchy collapses into NL.
ARTICLE Download: 48| View: 115| Comments: 0 | doi:10.20944/preprints202004.0057.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: COVID-19; social distancing model; sentiment analysis; physical distancing; social media; measuring attitudes
Online: 6 April 2020 (12:50:00 CEST)
The COVID-19 outbreak has focused attention on the use of social distancing as the primary defence against community infection, yet forcing social animals to maintain that physical distance has presented significant challenges for health authorities and law enforcement. Anecdotal media reports suggest widespread dissatisfaction with social distancing as a policy, yet there is little prior work aimed at measuring community acceptance of social distancing. In this paper, we propose a new approach to measuring attitudes towards social distancing by using social media and sentiment analysis. Over a 4 month period, we found 82.5% of tweets were in favour of social distancing. The results indicate a widespread acceptance of social distancing in the community. We conclude by examining options for estimating the optimal (minimal) social distance required at scale, and the implications for securing widespread community support and acceptance of public health messaging.
ARTICLE Download: 6| View: 12| Comments: 0 | doi:10.20944/preprints202004.0056.v1
Subject: Physical Sciences, General & Theoretical Physics Keywords: de Sitter; Anti de Sitter; group representation; hadronization; dark matter; zero-point energy; quark-gluon plasma; critical point
Online: 6 April 2020 (12:45:16 CEST)
An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.
ARTICLE Download: 25| View: 56| Comments: 0 | doi:10.20944/preprints202004.0055.v1
Subject: Engineering, General Engineering Keywords: Laser powder bed fusion; automatic quality assessment; machine learning; automatic relevance determination
Online: 6 April 2020 (12:41:05 CEST)
This study evaluates whether a combination of photodiode sensor measurements, taken during laser powder bed fusion (L-PBF) builds, can be used to predict the resulting build quality via a purely data-based approach. We analyse the relationship between build density and features that are extracted from sensor data collected from three diﬀerent photodiodes. The study uses a Singular Value Decomposition to extract lower-dimensional features from photodiode measurements, which are then fed into machine learning algorithms. Several unsupervised learning methods are then employed to classify low density (< 99% part density) and high density (≥ 99% part density) specimens. Subsequently, a supervised learning method (Gaussian Process regression) is used to directly predict build density. Using the unsupervised clustering approaches, applied to features extracted from both photodiode sensor data as well as observations relating to the energy transferred to the material, build density was predicted with up to 93.54% accuracy. With regard to the supervised regression approach, a Gaussian Process algorithm was capable of predicting the build density with a RMS error of 3.65%. The study shows, therefore, that there is potential for machine learning algorithms to predict indicators of L-PBF build quality from photodiode build-measurements. Moreover, the work herein describes approaches that are predominantly probabilistic, thus facilitating uncertainty quantiﬁcation in machine-learnt predictions of L-PBF build quality.
REVIEW Download: 75| View: 546| Comments: 0 | doi:10.20944/preprints202004.0054.v1
Subject: Engineering, Industrial & Manufacturing Engineering Keywords: pandemic; influenza pandemic; open source; open hardware; COVID-19; COVID-19 pandemic; medical hardware; open source medicine
Online: 6 April 2020 (12:38:59 CEST)
Distributed digital manufacturing offers a solution to medical supply and technology shortages during pandemics. To prepare for the next pandemic, this study reviews the state-of-the-art for open hardware designs needed in a COVID-19-like pandemic. It evaluates the readiness of the top twenty technologies requested by the Government of India. The results show that the majority of the actual medical products have had some open source development, however, only 15% of the supporting technologies that make the open source device possible are freely available. The results show there is still considerable work needed to provide open source paths for the development of all the medical hardware needed during pandemics. Five core areas of future work are discussed that include: i) technical development of a wide-range of open source solutions for all medical supplies and devices, ii) policies that protect the productivity of laboratories, makerspaces and fabrication facilities during a pandemic, as well as iii) streamlining the regulatory process, iv) developing Good-Samaritan laws to protect makers and designers of open medical hardware, as well as to compel those with knowledge that will save lives to share it, and v) requiring all citizen-funded research to be released with free and open source licenses.
ARTICLE Download: 8| View: 17| Comments: 0 | doi:10.20944/preprints202004.0053.v1
Subject: Life Sciences, Genetics Keywords: calcium signaling; chemokine signaling; gap junction; NOD-like receptor signaling; oli-neu cells; pannexin1; PI3K-Akt pathway; thyroid hormone pathway
Online: 6 April 2020 (12:36:20 CEST)
We profiled the transcriptomes of primary mouse cortical astrocytes cultured alone or co-cultured with immortalized precursor oligodendrocytes. The experimental set-up (insert systems) prevented formation of gap junction channels but allowed free exchange of the two culture media. The study complements our previously published reports that the genomic fabrics of major functional pathways in oligodendrocytes are substantially remodeled by the proximity of non-touching astrocytes. Here, we present new analysis indicating that the transcriptomic landscape of astrocytes likewise changes significantly in the proximity of non-touching oligodendrocytes. The research was stimulated by the reported transcriptomic similarity between the brains of Cx43KO and Cx32KO mice, both substantially different from that of the Cx36KO mice. Since the three connexins are expressed in different cell types (Cx43 in astrocytes, Cx32 in oligodendrocytes and Cx36 in neurons), altogether these findings support the idea of a “panglial transcriptomic syncytium” in the mouse brain. Going further, our results suggest that integration in a heterocellular tissue modulates not only the expression profile but also the expression control and networking of the genes in each cell phenotype.
ARTICLE Download: 42| View: 45| Comments: 0 | doi:10.20944/preprints202004.0052.v1
Subject: Medicine & Pharmacology, Other Keywords: novel coronavirus; epidemiology; COVID-19; epidemic model
Online: 6 April 2020 (12:30:42 CEST)
In the midst of the novel coronavirus (SARS-CoV-2) epidemic, examining reported case data could lead to biased speculations and conclusions. Indeed, estimation of unreported infections is crucial for a better understanding of the current emergency in China and in other countries. In this study, we aimed to estimate the unreported number of infections in China prior to 23 March 2020 restrictions. To do that, we developed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model which estimated unreported cases and infections from the reported number of deaths. Our approach relied on the fact that observed deaths were less likely to be affected by reporting biases than reported infections. Interestingly, we estimated that R0 was 2.43 (95%CI= 2.42 – 2.44) at the beginning of the epidemic, and that 92.9% (95%CI= 92.5% - 93.1%) of total cases were not reported. Similarly, the proportion of unreported new infections by day ranged from 52.1% to 100%, with a total of 91.8% (95%CI= 91.6% - 92.1%) unreported infections. Agreement between our estimates and those from previous studies proved that our approach was reliable to estimate prevalence and incidence of undocumented SARS-CoV2 infections. Once tested on Chinese data, our model could be applied on other countries with different surveillance and testing policies.
ARTICLE Download: 14| View: 19| Comments: 0 | doi:10.20944/preprints202004.0051.v1
Subject: Social Sciences, Marketing Keywords: problematic smartphone use; adolescence; marketing; unhook; gamification
Online: 6 April 2020 (11:46:48 CEST)
Background: Smartphones have become an indispensable part of the daily lives of adolescents in the 21st century, which is characterized by a highly digitized modern world. Besides their many advantages, smartphones might pave the way to compulsive usage and addictive experiences. To remedy this problem, this study proposes an authentic approach which integrates consumer behavior theories and techniques such as unhook and gamification. An education program has been designed based on these approaches to decrease the problematic smartphone use. Method: The participants of the education program consisted of 305 students (48.2% girls and 51.8% boys) with a mean age of 14.57 (SD = 0.74). The Demographic Form and Smartphone Addiction Scale for Adolescents (SASA) were conducted before the education program and three weeks after the education. Results: The results of the paired sample t-test analysis before and after the education program revealed that the SASA total scores decreased significantly (p < 0.01). There are significant differences in terms of gender, mothers’ education and class levels. Conclusion: This research emphasizes the role of an interdisciplinary approach to the addiction problem. The content used in the education program includes strategies that originally aimed at increasing consumption. The effectiveness of the program can be enhanced further in the future along with self-regulatory additions.
ARTICLE Download: 13| View: 45| Comments: 0 | doi:10.20944/preprints202004.0050.v1
Subject: Life Sciences, Biophysics Keywords: Banach–Tarski paradox; brain; power law; fractal; oscillations; information
Online: 6 April 2020 (11:36:49 CEST)
Neuroscientists are able to detect physical changes in information entropy in available neurodata. However, the information paradigm is inadequate to fully describe nervous dynamics and mental activities such as perception. This paper provides an effort to build explanations to neural dynamics alternative to thermodynamic and information accounts. We recall the Banach–Tarski paradox (BTP), which informally states that, when pieces of a ball are moved and rotated without changing their shape, a synergy between two balls of the same volume is achieved instead of the original one. We show how and why BTP might display this physical and biological synergy meaningfully, making it possible to tackle nervous activities. The anatomical and functional structure of the central nervous system’s nodes and edges allows to perform a sequence of moves inside the connectome that doubles the amount of available cortical oscillations. In particular, a BTP-based mechanism permits scale-invariant nervous oscillations to amplify and propagate towards far apart brain areas. Paraphrasing the BPT’s definition, we could state that: when a few components of a self-similar nervous oscillation are moved and rotated throughout the cortical connectome, two self-similar oscillations are achieved instead of the original one. Furthermore, based on topological structures, we illustrate how, counterintuitively, the amplification of scale-free oscillations does not require information transfer.
ARTICLE Download: 340| View: 868| Comments: 0 | doi:10.20944/preprints202004.0049.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Covid-19; epidemic in Italy; statistical forecast
Online: 6 April 2020 (11:28:31 CEST)
We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a ‘laboratory’ case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.
ARTICLE Download: 7| View: 15| Comments: 0 | doi:10.20944/preprints202004.0048.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: dissipativity analysis; generalized neural networks; Markovian jump parameters; stochastic disturbance
Online: 6 April 2020 (11:06:56 CEST)
This paper analyzes the robust dissipativity of uncertain stochastic generalized neural networks (USGNNs) with Markovian jumping parameters and time-varying delays. In practical applications most of the systems refer to uncertainties, hence, the norm-bounded parameter uncertainties and stochastic disturbance are considered. Then, by constructing an appropriate Lyapunov-Krasovskii functional (LKF) and by employing integral inequalities LMI-based sufficient conditions of the considered systems are established. Numerical simulations are given to show the merit of the presented results.
ARTICLE Download: 40| View: 125| Comments: 0 | doi:10.20944/preprints202004.0047.v1
Subject: Engineering, Civil Engineering Keywords: sustainable development; system resilience; resilient and sustainable infrastructure; pandemics; COVID-19
Online: 6 April 2020 (10:14:50 CEST)
Humanity’s social and economic development has been challenged by a range of adversities over the millennia that have caused widespread and unimaginable suffering. At the same time, these challenges have forced humans to evolve more wisely, overcoming adversity through creativity and leading to advancements in science and technology, medicine, ethics and legal systems, and socio-political systems. The dynamics of risks and opportunities caused by COVID-19, in the built, cyber, social and economic environments, present opportunities for deepening our understanding of resilient and sustainable development and infrastructure. This article reflects on five lessons that COVID-19 is teaching us about what it means to develop sustainably through the lens of transportation: (1) sustainable development planning and analytical frameworks must be comprehensive, for long-term sustainability; (2) multi-modal transportation is a superior vision for sustainable development than any one particular mode; (3) tele-activities are part of an effective infrastructure sustainability strategy; (4) economic capital is critically important to sustainable development even when it is not a critical existential threat, and, (5) effective social capital is essential in global disaster resistance and recovery, and can and must be leveraged between fast-moving and slow-moving disasters. Resilient and sustainable infrastructure will continue to be critical to addressing evolving natural and man-made hazards in the 21st Century.
ARTICLE Download: 7| View: 29| Comments: 0
Subject: Engineering, Automotive Engineering Keywords: autonomous vehicles; speed planning; optimization; required passing time; two-lane highways
Online: 6 April 2020 (09:48:27 CEST)
In passing maneuvers on two-lane highways, assessing the needed distance and the potential power reserve to ensure the required speed mode of the passing vehicle is a critical task of speed planning. This task must meet several mutually exclusive conditions that lead to successful maneuver. The paper addresses three main aspects. First, the issues of rational distribution of the speed of the passing vehicle for overtaking a long commercial vehicle on two-lane highways are discussed. The factors that affect maneuver effectiveness are analyzed, considering safety and cost. Second, a heuristic algorithm is then proposed based on the rationale for choosing the necessary space and time for overtaking. The initial prediction's sensitivity to fluctuations of current measurements of the position and speed of the overtaking participants is examined. Third, an optimization technique for passing vehicle speed distribution over the overtaking time using the finite element method is presented. The adaptive model predictive control is applied for tracking the references being generated. The presented model is illustrated using simulation.
REVIEW Download: 35| View: 60| Comments: 0 | doi:10.20944/preprints202004.0045.v1
Online: 6 April 2020 (09:28:00 CEST)
The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase (PARP) hyperactivated due to virus entry and extensive DNA damage sequentially leading to NAD+ depletion, ATP depletion and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection like the role of CD38 which functions as NADase and intensifies NAD depletion which in turn affects NAD+ dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a as one of the virus-encoded proteins induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.
ARTICLE Download: 8| View: 29| Comments: 0 | doi:10.20944/preprints202004.0044.v1
Subject: Biology, Plant Sciences Keywords: halophyte; salt-tolerance; N-nutrition; Portulaca oleracea; oxalic acid; ammonium nutrition
Online: 6 April 2020 (09:21:14 CEST)
Halophytic plants are, by definition, well adapted to saline soils. However, even halophytes can face nutritional imbalance and accumulation of high levels of compounds such as oxalic acid (OA), and nitrate (NO3¯). These compounds compromise the potential nutritional health benefits associated with salt tolerant plants such as Portulaca oleracea. Thus, preventing the accumulation of non-nutritional compounds will allow plants to be grown in saline conditions as crops. To this end, two ecotypes (ET and RN) of Portulaca oleracea plants were grown under growth room conditions with two levels of salinity (0, 50 mM NaCl) and three ratios of nitrate: ammonium (0:100%; 33:66%; 25:75% NO3¯:NH4+). The results showed that both ecotypes exposed to elevated NO3¯, showed severe leaf chlorosis, high levels of OA, citric acid, and malic acid, while plants of ecotype ET exposed to elevated NH4+ concentrations (33% and 75%) and 50 mM NaCl displayed a marked reduction in OA content, increased total chlorophyll and carotenoid contents, crude protein content, total fatty acid (TFA) and α-Linolenic acid (ALA) thus enhancing leaf quality. This opens the potential to grow high biomass, low OA P. oleracae crops. Lastly, our experiments suggest that ecotype ET copes with saline conditions and elevated NH4+ through shifts in leaf metabolites.
BRIEF REPORT Download: 8| View: 19| Comments: 0 | doi:10.20944/preprints202004.0043.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: lactation; physiology-based lactation models; drug exposure prediction; fasting; drug safety; newborn; infant; human milk
Online: 6 April 2020 (09:11:05 CEST)
There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.
ARTICLE Download: 11| View: 37| Comments: 0 | doi:10.20944/preprints202004.0042.v1
Subject: Engineering, Automotive Engineering Keywords: autonomous vehicles; parking; path planning; space restrictions; optimization
Online: 6 April 2020 (07:26:45 CEST)
The paper presents models of path and control planning for parking, docking, and movement of autonomous vehicles at low speeds considering space constraints. Given the low speed of motion, and in order to test and approve the proposed algorithms, vehicle kinematic models are used. Recent works on the development of parking algorithms for autonomous vehicles are reviewed. Bicycle kinematic models for vehicle motion are considered for three basic types of vehicles: passenger car, long wheelbase truck, and articulated vehicles with and without steered semitrailer axes. Mathematical descriptions of systems of differential equations in matrix form and expressions for determining the linearization elements of nonlinear motion equations that increase the speed of finding the optimal solution are presented. Options are proposed for describing the interaction of vehicle overall dimensions with the space boundaries, within which a maneuver should be performed. An original algorithm that considers numerous constraints is developed for determining vehicle permissible positions within the closed boundaries of the parking area, which are directly used in the iterative process of searching for the optimal plan solution using nonlinear model predictive control (NMPC). The process of using NMPC to find the best trajectories and control laws while moving in a semi-limited space of constant curvature (turnabouts, roundabouts) are described. Simulation tests were used to validate the proposed models for both constrained and unconstrained conditions and the output (state-space) and control parameters' dependencies are shown. The proposed models represent an initial effort to model the movement of autonomous vehicles for parking and has the potential for other highway applications.
ARTICLE Download: 22| View: 35| Comments: 0 | doi:10.20944/preprints202004.0041.v1
Online: 6 April 2020 (07:25:12 CEST)
COVID-19 (SARS-Cov-2) is spreading around the globe in a highly contagious manner. China has shown the way to halt the progression of the disease by totally sealing Wuhan from rest of china but they could not prevent community spread resulting in more than 4000 deaths in a short period of time. India, following example of china, ordered national Lockdown early on 23 March, 2020. But it is difficult to determine the transition Here we have changed the way we look at available data to detect an early onset of the effect of Lockdown. Here a simple method is described for the first time to determine at the earliest when a change is beginning to take effect after Lockdown on the progression/regression of the spread of novel COVID-19 virus which could help to frame strategy for intervention to prevent community spread and save lives.
Fri, 3 April 2020
ARTICLE Download: 20| View: 49| Comments: 0 | doi:10.20944/preprints202004.0035.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: research data management; FAIR; file structure; file system
Online: 3 April 2020 (15:56:22 CEST)
Storing scientific data on the file system in a meaningful and transparent way is no trivial task. In particular when the data have to be accessed after their originator has left the lab the importance of a standardized file structure cannot be underestimated. It is desirable to have a structure that allows for the unique categorization of all kinds of data from experimental results to publications. It has to be accessible to a broad variety of workflows, e.g., via graphical user interface as well as via command line, in order to find widespread acceptance. Furthermore, the inclusion of already existing data has to be as simple as possible. We propose a three-level structure to organize and store scientific data that incorporates the full chain of scientific data management from data acquisition to analysis to publications. Metadata are saved in a standardized way and connect original data to analyses and publication as well as to their originators. A simple software tool to check a file structure for compliance with the proposed structure is presented.
REVIEW Download: 123| View: 293| Comments: 3 | doi:10.20944/preprints202004.0040.v1
Subject: Life Sciences, Virology Keywords: Dengue; COVID-19; SARS-CoV-2; epidemiology; infection; mortality; cross-protection; Dengue vaccine; ELISA; Dengvaxia
Online: 3 April 2020 (15:48:36 CEST)
We observed that global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries where dengue is highly endemic (>1.5 million cases/year) appear to be less hit by COVID-19 pandemic in terms of infection and transmission. Other evidences also support our proposition that pre-exposure to other wide-spread viral infections like dengue may thwart the spread of the COVID-19 pandemic.
ARTICLE Download: 16| View: 42| Comments: 0 | doi:10.20944/preprints202004.0039.v1
Subject: Engineering, Mechanical Engineering Keywords: IoT device; Convolutional neural network; RMSprop algorithm; Continue wavelet transform; , Chain sprocket drive; Wireless MEMS accelerometer
Online: 3 April 2020 (15:38:55 CEST)
This paper proposes a health monitoring method for the early detection of defects in a chain sprocket drive (CSD) system and classification of fault types before a catastrophic failure occurs. In the operation of a CSD system, the early detection of defects is very useful to prevent system failure. Specially, if the type of defect is known, it will be easy to find a method to fix it. In this work, eight fault types in the components of the CSD system, such as the gear tooth, bearings, and shaft of the drive motor, were arbitrarily made and assembled. To detect the fault signals during the CSD system operation, the vibration is measured by an Internet of Things (IoT) device, which features a wireless MEMS accelerometer, Bluetooth function, Wi-Fi function, and battery. The IoT device is mounted on the gearbox housing. The measured one-dimensional vibration time-series is transformed into time-scale images by continuous wavelet transform (CWT). A convolution neural network (CNN) is employed to extract deep features embedded in the images, which are closely related to fault types. To update the learning parameters of the CNN, the RMSprop learning algorithm is applied, and the CNN is trained using 500 image samples. Multiple classification performance of the trained network is tested using 100 image samples. Feature maps for different fault types are obtained from the final convolution layer of the CNN. For the visualization of fault types, t-stochastic neighbor embedding is employed and applied to the feature maps to convert high-dimensional data into two-dimensional data. Two-dimensional features enabled excellent classification of the eight fault types and one normal type.
ARTICLE Download: 12| View: 29| Comments: 0
Subject: Mathematics & Computer Science, Analysis Keywords: asymptotic expansion; Borel-Laplace transform; Fourier transform; initial value problem; formal power series; partial differential equation; singular perturbation
Online: 3 April 2020 (15:35:10 CEST)
The work is devoted to the study of a family of linear initial value problems of partial differential equations in the complex domain, dealing with two complex time variables. The use of a truncated Laplace-like transformation in the construction of the analytic solution allows to overcome a small divisor phenomenon arising from the geometry of the problem and represents an alternative approach to the one proposed in a recent work by the last two authors. The result leans on the application of a fixed point argument and the classical Ramis-Sibuya theorem.
REVIEW Download: 12| View: 19| Comments: 0
Subject: Engineering, General Engineering Keywords: cloud computing; cloud broker; PuLSAR; IaaS; PaaS; SaaS; QoS; SOS
Online: 3 April 2020 (15:31:23 CEST)
Abstract—as the complexity in the cloud services increases day by day the role of brokers used in the cloud gain more importance. Here we basically resolve this issue by discussing preference based cloud service recommender that support MCDM approach. The implementation and specifications details are properly discussed in a unified way to deal with the problem. SC3 is a tool that compromises capabilities of the quality assurance dimension of CSB and also it strengthen the flexibility of cloud services. The anxieties between definition procedure and implementation procedure are separated by service completeness compliance checker (SC3). Now a days companies use cloud computing for their economic benefits and market competitions that increase the demand of “cloud computing”. So for the calculation of critical success factor of “cloud computing” we focus on plan do check act strategy.
ARTICLE Download: 6| View: 16| Comments: 0 | doi:10.20944/preprints202004.0036.v1
Subject: Physical Sciences, Mathematical Physics Keywords: Bell theorem; Local function computer program; Violation CHSH
Online: 3 April 2020 (15:29:01 CEST)
If a clear and valid no-go for Einsteinian hidden parameters is real, it must in no way be possible to violate the CHSH with a local hidden variables based computer simulation. In the paper we show that with the use of a modied Glauber-Sudarshan method it is possible to violate the CHSH.The criterion value comes close to the quantum value and is approximately 2.4. The proof (POC) is presented with the use of an R computer program. The important snippets of the code are discussed and the complete code is presented in an appendix.
REVIEW Download: 50| View: 115| Comments: 1 | doi:10.20944/preprints202004.0019.v2
Online: 3 April 2020 (15:23:50 CEST)
OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2.MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the keywords “severe acute respiratory syndrome coronavirus”, “2019-nCoV”, “COVID-19, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection.RESULTS: The global cases of COVID-19 as of April 2, 2020 have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness.Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from a underlying chronic medical condition like hypertension, diabetes, cancer, respiratory illness or cardiovascular diseases.CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.
ARTICLE Download: 14| View: 29| Comments: 0 | doi:10.20944/preprints202004.0034.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: Shannon entropy; Hurst exponent; Amino acid; Frequency distribution; \& SARS-CoV2
Online: 3 April 2020 (15:10:51 CEST)
The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.
ARTICLE Download: 37| View: 79| Comments: 1 | doi:10.20944/preprints202004.0015.v2
Online: 3 April 2020 (15:08:50 CEST)
Ligand and structure based virtual screening approaches were applied to clinical stage drugs as well as those approved for human use in an attempt to repurpose drugs for potential use against COVID-19. This approach involved ligand-based shape similarity searches, structure-based docking and pharmacophore searches with the help of pharmacophore queries derived from available ligands and receptor structures. Several compounds appeared as hits in pharmacophore and shape similarity searches and those docking to the SARS-CoV-2 viral 3CL protease were then ranked on the basis of docking scores.
ARTICLE Download: 10| View: 10| Comments: 0
Subject: Physical Sciences, Optics Keywords: integrated waveguides; nonlinear optics; 2D; materials; silicon nanophotonics graphene
Online: 3 April 2020 (14:09:34 CEST)
Layered two-dimensional (2D) GO films are integrated with silicon-on-insulator (SOI) nanowire waveguides to experimentally demonstrate an enhanced Kerr nonlinearity, observed through self-phase modulation (SPM). The GO films are integrated with SOI nanowires using a large-area, transfer-free, layer-by-layer coating method that yields precise control of the film thickness. The film placement and coating length are controlled by opening windows in the silica cladding of the SOI nanowires. Owing to the strong mode overlap between the SOI nanowires and the highly nonlinear GO films, the Kerr nonlinearity of the hybrid waveguides is significantly enhanced. Detailed SPM measurements using picosecond optical pulses show significant spectral broadening enhancement for SOI nanowires coated with 2.2-mm-long films of 1−3 layers of GO, and 0.4-mm-long films with 5−20 layers of GO. By fitting the experimental results with theory, the dependence of GO’s n2 on layer number and pulse energy is obtained, showing interesting physical insights and trends of the layered GO films from 2D monolayers to quasi bulk-like behavior. Finally, we show that by coating SOI nanowires with GO films the effective nonlinear parameter of SOI nanowires is increased 16 fold, with the effective nonlinear figure of merit (FOM) increasing by about 20 times to FOM > 5. These results reveal the strong potential of using layered GO films to improve the Kerr nonlinear optical performance of silicon photonic devices.
ARTICLE Download: 12| View: 19| Comments: 0 | doi:10.20944/preprints202004.0032.v1
Subject: Earth Sciences, Geoinformatics Keywords: indoor positioning system; image-based positioning system; computer vision; SIFT; feature detection; feature description; cell phone camera; PnP problem; projection matrix; epipolar geometry; OpenCV
Online: 3 April 2020 (11:59:48 CEST)
As people grow a custom to effortless outdoor navigation there is a rising demand for similar possibility indoors as well. Unfortunately, indoor localization, being one of the necessary requirements for navigation, continues to be problem without a clear solution. In this article we are proposing a method for an indoor positioning system using a single image. This is made possible using small preprocessed database of images with known control points as the only preprocessing needed. Using feature detection with SIFT algorithm we can look through the database and find image which is the most similar to the image taken by user. Pair of images is then used to find coordinates of database image using PnP problem. Furthermore, projection and essential matrices are determined allowing for the user image localization ~ determining the position of the user in indoor environment. Benefits of this approach lies in the single image being the only input from user and no requirements for new onsite infrastructure and thus enables a simpler realization for the building management.
ARTICLE Download: 434| View: 227| Comments: 0 | doi:10.20944/preprints202004.0031.v1
Subject: Keywords: Saudi Arabia, COVID-19, Sentiment Analysis, Twitter, Measures
Online: 3 April 2020 (11:45:33 CEST)
Background: Countries around the world are facing extraordinary challenges in implementing various measures to slow down the spread of the novel coronavirus (COVID-19). Guided by international recommendations, Saudi Arabia has implemented a series of infection control measures after the detection of the first confirmed case in the country. However, in order for these measures to be effective, public attitudes and compliance must be conducive as perceived risk is strongly associated with health behaviors. The primary objective of this study is to assess Saudis’ attitudes towards COVID-19 preventive measures to guide future health communication content. Methods: Naïve Bayes machine learning model was used to run Arabic sentiment analysis of Twitter posts through the Natural Language Toolkit (NLTK) library in Python. Tweets containing hashtags pertaining to seven public health measures imposed by the government were collected and analyzed. Results: A total of 53,127 tweets were analyzed. All measures, except one, showed more positive tweets than negative. Measures that pertain to religious practices showed the most positive sentiment. Discussion: Saudi Twitter users showed support and positive attitudes towards the infection control measures to combat COVID-19. It is postulated that this conducive public response is reflective of the overarching, longstanding popular confidence in the government. Religious notions may also play a positive role in preparing believers at times of crises. Findings of this study broadened our understanding to develop proper public health messages and promote stronger compliance with control measures to control COVID-19.
ARTICLE Download: 20| View: 32| Comments: 0 | doi:10.20944/preprints202004.0029.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Mobility; infrastructure; flexible pavement; pavement condition index (PCI); international roughness index (IRI); artificial intelligence (AI); predictive models; ensemble learning; structural health monitoring; machine learning
Online: 3 April 2020 (09:35:44 CEST)
The construction of different roads, such as freeways, highways, major roads or minor roads must be accompanied by constant monitoring and evaluation of service delivery. Pavements are generally assessed by engineers in terms of the smoothness, surface condition, structural condition and surface safety. Pavement assessment is often conducted using the qualitative indices such as international roughness index (IRI), pavement condition index (PCI), structural condition index (SCI) and skid resistance value (SRV), which are used for smoothness assessment, surface condition assessment, structural condition assessment, and surface safety assessment, respectively. In this paper, Tehran-Qom Freeway in Iran has been selected as the case study and its smoothness and pavement surface conditions are assessed. At 2-km intervals, a 100-meter sample unit is selected in the slow-speed lane (totally, 118 sample units). In these sample units, the PCI is calculated after a visual inspection of the pavement and the recording of distresses. Then, in each sample unit, the average IRI is computed. The purpose of this study is to provide a method for estimating PCI based on IRI. The proposed theory was developed by Random Forest (RF), and Random Forest optimized by Genetic Algorithm (RF-GA) methods and these methods were validated using correlation coefficient (CC), scattered index (SI), and Willmott’s index of agreement (WI) criteria. The proposed method reduces costs, saves time and eliminates the safety risks.
REVIEW Download: 15| View: 24| Comments: 0 | doi:10.20944/preprints202004.0028.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: brain organoids; stem cells; brain in a vat
Online: 3 April 2020 (08:14:18 CEST)
Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).
ARTICLE Download: 7| View: 18| Comments: 0 | doi:10.20944/preprints202004.0027.v1
Subject: Engineering, Other Keywords: wildfire smoke detection; target-aware; depthwise separable; fixed convolution kernel; DSATA
Online: 3 April 2020 (04:43:58 CEST)
Since smoke usually occurs before a flame arises, fire smoke detection is especially significant for early warning systems. In this paper, a DSATA(Depthwise Separability And Target Awareness) algorithm based on depthwise separability and target awareness is proposed. Existing deep learning methods with convolutional neural networks pretrained by abundant and vast datasets are always used to realize generic object recognition tasks. In the area of smoke detection, collecting large quantities of smoke data is a challenging task for small sample smoke objects. The basis is that the objects of interest can be arbitrary object classes with arbitrary forms. Thus, deep feature maps acquired by target-aware pretrained networks are used in modelling these objects of arbitrary forms to distinguish them from unpredictable and complex environments. In this paper, this scheme is introduced to deal with smoke detection. The depthwise separable method with a fixed convolution kernel replacing the training iterations can improve the speed of the algorithm to meet the enhanced requirements of real-time fire spreading for detecting speed. The experimental results demonstrate that the proposed algorithm can detect early smoke, is superior to the state-of-the-art methods in accuracy and speed, and can also realize real-time smoke detection.
ARTICLE Download: 11| View: 22| Comments: 0 | doi:10.20944/preprints202004.0026.v1
Subject: Physical Sciences, General & Theoretical Physics Keywords: quantum cosmology; the problem of the time; initial conditions in the quantum universe; quantum gravity
Online: 3 April 2020 (04:36:11 CEST)
We argue that the problem of time is not a crucial issue inherent in the quantum picture of the universe evolution. On the minisuperspace model example with the massless scalar field, we demonstrate four approaches to the description of quantum evolution, which give similar results explicitly. The relevance of these approaches to building a quantum theory of gravity is discussed.
CONCEPT PAPER Download: 21| View: 25| Comments: 0 | doi:10.20944/preprints202004.0025.v1
Subject: Biology, Other Keywords: historical kinds; individuation; cultural evolution; evolutionary innovation
Online: 3 April 2020 (04:28:34 CEST)
Since its inception, evolutionary theory has experienced a number of extensions. The most important of these took the forms of the Modern Evolutionary Synthesis (MES), embracing genetics and population biology in the early 20th century, and the Extended Evolutionary Synthesis (EES) of the last thirty years, embracing, among other factors, non-genetic forms of inheritance. While we appreciate the motivation for this recent extension, we argue that it does not go far enough, since it restricts itself to widening explanations of adaptation by adding mechanisms of inheritance and variation. Here we argue that a more thoroughgoing extension is needed, one that broadens the explanatory scope of evolutionary theory. In addition to adaptation and its various mechanisms, evolutionary theory must recognize as a distinct intellectual challenge the origin of what we call “historical kinds.” Under historical kinds we include any process that acquires a quasi-independent and traceable lineage-history in biological and cultural evolution. A limited number of historical kinds have been recognized in evolutionary biology, and corresponding research programs have been formed around them. The best characterized examples are biological species and genes. We propose that the conceptual category of historical kinds can and needs to be extended, and we develop the notion of a historical kind in a series of paradigmatic exemplars, from genes and cell types to rituals and music. The explanation of the origin of historical kinds should be a main objective of biological and cultural sciences.
BRIEF REPORT Download: 77| View: 225| Comments: 0 | doi:10.20944/preprints202004.0024.v1
Subject: Life Sciences, Virology Keywords: COVID-19; SARS-nCoV-2; vaccine; antibody; immune escape; variant; spike protein; genomic drift; convalescent plasma
Online: 3 April 2020 (04:24:52 CEST)
New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.
HYPOTHESIS Download: 618| View: 1079| Comments: 3 | doi:10.20944/preprints202004.0023.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; bradykinin; ACE2; pulmonary angioedema; ARDS; icatibant
Online: 3 April 2020 (04:13:43 CEST)
Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.
COMMUNICATION Download: 74| View: 130| Comments: 0
Subject: Life Sciences, Virology Keywords: anti-viral; COVID-19, SARS-CoV-2; autophagy; chloroquine; hydroxychloroquine; immunology; infection; inflammation; lysophagy; microbiology; Plaquenil; SARS; virophagy
Online: 3 April 2020 (03:57:49 CEST)
At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One of the most recent has drawn worldwide hype to the possible benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of these articles evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss some pros and cons concerning the current therapeutic options targeting this process.
CONCEPT PAPER Download: 165| View: 383| Comments: 0 | doi:10.20944/preprints202004.0021.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; face masks; epidemiology; coronavirus; pandemics
Online: 3 April 2020 (03:47:23 CEST)
The US and UK governments, as well as the World Health Organization, currently advise against the use of masks by the public to fight the ongoing Coronavirus Disease 19 (COVID-19) pandemic (1). But could they be wrong? The governments of China, South Korea, Hong Kong, Viet Nam, Czechia, Slovakia, Bosnia and Taiwan all recommend that the public wear masks to slow the spread of the coronavirus. In some countries, like Japan, masks aren’t officially recommended, but are still widely used by the public. Many countries treat masks as a strategic resource. China has ramped up production of facemasks, converting Foxconn factories that once made iPhones to make face masks. Taiwan has also ramped up the production of facemasks, prohibited their export, and implemented price controls and rationing. It’s hard to see how both approaches could be right. Increasingly, advice against the use of face masks has been questioned (1) (2) (3), including by the head of China’s CDC (4). Common sense, scientific studies, but perhaps most of all the success of countries using masks to fight the coronavirus suggest that masks may make a difference. There are fewer scientific studies available to guide decision making than we might like, and the evidence is not always clear-cut. However, decision-making in a crisis requires that decisions be made in the absence of perfect clarity. What is clear is that the exponential mathematics of pandemics mean that even if masks are of limited benefit in reducing infection rates, masks could make a large difference over time, potentially slowing the pace of the pandemic, limiting its spread, saving lives, and finally, letting countries to restart the economies that their people depend on for their livelihoods.
ESSAY Download: 15| View: 20| Comments: 1 | doi:10.20944/preprints202002.0298.v3
Subject: Engineering, Energy & Fuel Technology Keywords: photovoltaics; solar energy; Father Verspieren; solar energy in Africa; rainwater harvesting; solar pump
Online: 3 April 2020 (03:38:43 CEST)
Almost fifty years after the first installations, I identify the main lessons learned from fighting drought and poverty in Africa with direct solar-powered pumps thanks to Father Bernard Verspieren and Mali Aqua Viva. Six main findings and three main recommendations emerge from the present analysis. They are of direct relevance to all Africa’s countries whose population has gone from 438 million in 1977 to 1,308 million in 2019, with about 600 million still having no access to electricity. In place of “awareness campaigns” and extraordinary courses held by international organizations, I recommend to establish national solar energy institutes whose task will include the education of solar energy professionals giving practice-oriented workshops on solar-powered drip irrigation and rainwater harvesting throughout each Africa’s country. Said education will critically include the economic and social aspects of distributed “generation” of energy and water from sunlight and rainfall.
ARTICLE Download: 8| View: 15| Comments: 0 | doi:10.20944/preprints202004.0020.v1
Subject: Engineering, General Engineering Keywords: shakedown; plasticity; limit design; ratcheting; experimental comparison; residual displacement
Online: 3 April 2020 (03:35:36 CEST)
Safety assessment of structures can be obtained by means of limit design in order to overcome uncertainties concerning actual response due to inelastic constitutive behaviour and more generally to non-linear structural response and loads’ random variability. The limit analysis is used for evaluating the safety of the structures directly starting from load level without any knowledge of the load history. In the paper, the lower bound calculation is proposed based on permanent strain parametric description of the residual stress. The strategy allows considering the permanent strain as the effective parameters of the procedure and can be used to control the ductility requirements until complete load program develops. In this way one can control if the structure can develop entirely its possibility of plastic adaptation up to required load level. The procedure is compared to experimental results obtained on aluminium beams in shake down.
Thu, 2 April 2020
ARTICLE Download: 39| View: 81| Comments: 1 | doi:10.20944/preprints202002.0379.v4
Subject: Mathematics & Computer Science, Computational Mathematics Keywords: complexity classes; regular languages; reduction; number theory; conjecture; primes
Online: 2 April 2020 (18:25:32 CEST)
The strong Goldbach's conjecture states that every even integer greater than 2 can be written as the sum of two primes. The conjecture that all odd numbers greater than 7 are the sum of three odd primes is known today as the weak Goldbach conjecture. A principal complexity class is NSPACE(S(n)) for some S(n). We show if the weak Goldbach's conjecture is true, then the problem PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n). However, if this happens, then the strong Goldbach's conjecture is true or this has an infinite number of counterexamples. In addition, if this happens, then the Twin prime conjecture is true. Moreover, if this happens, then the Beal's conjecture is true. Furthermore, if this happens, then the Riemann hypothesis is true. Since the weak Goldbach's conjecture was proven, then this will certainly happen.
REVIEW Download: 57| View: 85| Comments: 0 | doi:10.20944/preprints202004.0019.v1
Online: 2 April 2020 (12:20:19 CEST)
OBJECTIVE: Recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), another member of coronavirus family is an ongoing worldwide life-threatening crisis. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2. MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the key words “severe acute respiratory syndrome coronavirus”, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information attained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection. RESULTS: The global cases of COVID-19 till 30th March 2020 have rose more than 700,000 and morbidity has gone more than 37,000. The infection rate for COVID-19 has been predicted to be higher than the previous outbreaks of same family members, that includes the SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness. High risk includes elderly people and patients with weak immune system or suffering from chronic medical condition like hypertension, diabetes, cancer, respiratory illness and cardiovascular diseases. CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, affecting almost each and every country on globe. As there is still growing understanding of SARS-CoV-2 in relation to its virology, epidemiology and clinical management strategies, we need to learn our lessons to conceive comprehensive measures to prevent such outbreaks in future.
REVIEW Download: 21| View: 34| Comments: 1 | doi:10.20944/preprints202002.0374.v2
Online: 2 April 2020 (12:16:16 CEST)
The parasitic mite, Varroa destructor, has shaken the beekeeping and pollination industries since its spread from its native host, the Asian honey bee (Apis cerana), to the naïve European honey bee (A. mellifera) used commercially for pollination and honey production around the globe. Varroa is the greatest threat to honey bee health. Worrying observations include increasing acaricide resistance in the varroa population and sinking economic treatment thresholds, suggesting that the mites or their vectored viruses are becoming more virulent. Highly infested weak colonies facilitate mite dispersal and disease transmission to stronger and healthier colonies. Here, we review recent developments in the biology, pathology and management of varroa, and integrate older knowledge that is less well known.