Traveling Wave Solution to Two-Dimensional Burgers-Korteweg-De Vries Equation

In this thesis, we study the Two-Dimensional Burgers-Korteweg-de Vries (2D-BKdV) equation by analyzing the equivalent Abel equation, which indicates that under some particular conditions, the 2D-BKdV equation has a unique bounded traveling wave solution. By using the theorem of contractive mapping, a traveling wave solution to the 2D-BKdV equation is expressed explicitly. In the end, the behavior of the proper solution of the 2D-BKdV equation is established by applying the comparison theorem of differential equations

Halogen Bonding Increases the Potency and Isozyme-selectivity of Protein Arginine Deiminase 1 Inhibitors

Protein Arginine Deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure-activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology

Limitations and Improvements of the Intelligent Driver Model (IDM)

This contribution analyzes the widely used and well-known "intelligent driver model" (briefly IDM), which is a second order car-following model governed by a system of ordinary differential equations. Although this model was intensively studied in recent years for properly capturing traffic phenomena and driver braking behavior, a rigorous study of the well-posedness of solutions has, to our knowledge, never been performed. First it is shown that, for a specific class of initial data, the vehicles' velocities become negative or even diverge to $-\infty$ in finite time, both undesirable properties for a car-following model. Various modifications of the IDM are then proposed in order to avoid such ill-posedness. The theoretical remediation of the model, rather than post facto by ad-hoc modification of code implementations, allows a more sound numerical implementation and preservation of the model features. Indeed, to avoid inconsistencies and ensure dynamics close to the one of the original model, one may need to inspect and clean large input data, which may result practically impossible for large-scale simulations. Although well-posedness issues occur only for specific initial data, this may happen frequently when different traffic scenarios are analyzed, and especially in presence of lane-changing, on ramps and other network components as it is the case for most commonly used micro-simulators. On the other side, it is shown that well-posedness can be guaranteed by straight-forward improvements, such as those obtained by slightly changing the acceleration to prevent the velocity from becoming negative.Comment: 29 pages, 23 Figure

The succession of rhizosphere microbial community in the continuous cropping soil of tobacco

Introduction: Flue-cured tobacco is an important economic crop that is not tolerant of continuous cropping and can be influenced by planting soil conditions including rhizosphere microbial communities and soil physicochemical properties. The relationship between rhizosphere microbial communities and soil physicochemical properties under continuous cropping conditions is unclear.Methods: This study investigated the succession of rhizosphere microbial community in continuous tobacco cropping soil for 1, 3, 5, 8, 10, 15, and 30 years. The physicochemical properties of the soil were measured, high-throughput sequencing was performed on the rhizosphere microbial community, and correlation analysis was conducted.Results: The results suggested that continuous cropping could significantly enrich soil available nitrogen, available phosphorus, available potassium, and organic matter. Meanwhile, the alpha diversity of the bacterial community was significantly reduced with continuous cropping, indicating significant changes in the structure of bacterial and fungal communities. Based on linear discriminant analysis effect size (LEfSe), 173 bacterial and 75 fungal genera were identified with significant differences. The bacterial genera, Sphingomonas, Streptomyces, and Microvirga, were significantly positively correlated with continuous cropping years. The fungal genera, Tausonia, Solicocozyma, Pseudomycohila, and Fusarium, also showed significant positive correlation with continuous cropping years. Meanwhile, the fungal genera, Olpidium, Cephaliophora, and Cercophora, presented an opposite correlation. However, there are differences in the correlation between these bacterial and fungal genera related to continuous cropping years and other different soil physicochemical properties.Discussion: In summary, this work could provide a reference for soil management and scientific fertilization of tobacco under continuous cropping conditions

Eluding innate immune responses by IBV: role of non-structural protein 15

Upon virus infection, cells of the host develop various anti-viral defenses while viruses in turn have evolved strategies to antagonize the host defenses. This arms race between the viral antagonistic strategies and the host anti-viral defenses determines the final outcome of a virus infection. Knowledge on this virus-host arms race is crucial to understand the viral pathogenicity, and to develop anti-viral therapeutics. Coronaviruses (CoVs) are a group of RNA viruses that encode structural, non-structural and accessory proteins. The non-structural and accessory proteins, although not being part of the viral particles, usually play important roles in the aforementioned virus-host arms race. Infectious Bronchitis, caused by γ-CoV Infectious Bronchitis Virus (IBV), is an economically important disease of chickens and other fowl. IBV targets the upper respiratory tract causing near complete morbidity and high rates of mortality. Type I interferon plays a crucial role in fighting the virus infection and regulating the immune system of the host. It was previously reported that IBV resists the activity of type I interferon and suggests an important role of the four accessory proteins (3a, 3b, 5a, 5b). However, the roles of the non-structural proteins of IBV still remained to be addressed. Non-structural protein (nsp)15 of CoVs is an endoribonuclease (EndoU) that catalyzes the breakdown of RNAs. The role of the nsp15 EndoU of IBV in the IBV-host arms race was not investigated before. In this thesis, we describe for the first time the role of nsp15 EndoU in IBV’s antagonism against interferon-β (IFN-β) activity, as well as the activation of the protein kinase R (PKR)-pathway and the formation of stress granules (SGs). Following transfection of a plasmid encoding IBV nsp15, we demonstrate that the overexpressed IBV nsp15 inhibits global protein synthesis in the transfected cells. The EndoU activity of IBV nsp15 appears indispensable for the above-described inhibitory effect, implying that nsp15 EndoU targets cellular substrates. Suppression of host translation machinery is usually fine-tuned by the virus to avoid interference with the synthesis of viral proteins. In this thesis we also investigate how the role of nsp15 EndoU is fine-tuned during IBV infection to the advantage of IBV replication.In chapter 1, we generally introduce CoVs and particularly IBV, the induction of host anti-viral defenses, and the viral strategies to antagonize these host defenses. In chapter 2, we describe an improved protocol of CoV reverse genetics, via which a nsp15 EndoU-deficient recombinant mutant IBV was successfully retrieved. In chapter 3, we demonstrate that, compared to the wild type IBV, the EndoU-deficient rIBV-nsp15H238A generated more double stranded RNA (dsRNA), a molecule generated during IBV infection that is able to induce host defenses. Accordingly, the rIBV-nsp15H238A induced stronger dsRNA-induced anti-viral responses including IFN-β induction and PKR phosphorylation-mediated stress granules (SGs) formation. In chapter 4, we show that the overexpressed IBV nsp15 obtained by transfection inhibits the global protein synthesis in the transfected cells, for which the EndoU activity is indispensable. We discovered that the above-mentioned inhibition of global protein synthesis is via a cytoplasmic poly (A) binding protein (PABPC1) nuclear localization-involved mechanism. In addition, the above inhibition of global protein synthesis is conserved across nsp15 EndoU of α-CoVs (PEDV, TGEV) and β-CoVs (SARS-CoV-1, MERS-CoV, SARS-CoV-2). Together, via overexpressing nsp15 EndoU alone, we demonstrate that nsp15 EndoU of γ-CoV IBV, α-CoVs and β-CoVs, inhibits protein synthesis in the transfected cells. This suggests, for the first time, that nsp15 EndoU of CoVs targets cellular substrates of the host. In chapter 5, we show that both the wild type IBV and the EndoU-deficient rIBV-nsp15H238A induce host shutoff, albeit via different mechanisms. The rIBV-nsp15H238A-induced host shutoff does not benefit viral replication as it does not restrict the capacity for SGs formation or production of IFN-β. In chapter 4, we showed that IBV nsp15 EndoU inhibits protein synthesis in cells via a mechanism related to a nuclear localization of PABPC1. The IBV nsp15 EndoU-induced nuclear localization of PABPC1 was not detected after the wild type IBV infection, suggesting that IBV nsp15’s inhibitory effect of global protein synthesis in the host cells may be fine-tuned during IBV infection. Previous reports showed that PABPC1 is likely involved in CoV replication, and we therefore hypothesize that fine-tuning nsp15’s EndoU activity is a viral tactic to avoid interference with the viral replication. In addition, we describe two possible mechanisms how IBV nsp15’s EndoU activity is fine-tuned during IBV infection. One mechanism is related to the subcellular localization of nsp15 EndoU during IBV infection, which might separate nsp15 EndoU from its cellular substrates. Double membrane vesicles (DMVs), concentrated in the perinuclear area, are central hubs for the replication and transcription complex (RTC)-mediated synthesis of viral RNA. CoV nsp15 is likely associated with RTC as MHV nsp15 was previously reported to strongly colocalize with two RTC proteins nsp8, nsp12. We observed a perinuclear aggregation of nsp15 EndoU during IBV infection, implying that IBV nsp15 EndoU is located inside DMVs and separated from its cellular substrates. The other mechanism is mediated by the interaction between nsp15 EndoU and other IBV nsps. We demonstrated that the overexpressed nsp2, nsp7 or nsp16 of IBV restored nsp15 EndoU’s inhibition of global protein synthesis in the transfected cells. In chapter 6, I put the findings in this thesis on the nsp15 EndoU of IBV into the context of nsp15 EndoU of CoVs in general.In conclusion, the work described in this thesis demonstrates for the first time how nsp15 EndoU of IBV antagonizes dsRNA-induced anti-viral defenses. Also, this thesis demonstrates the regulation mechanisms of the role of nsp15 EndoU to avoid reduced IBV replication. In addition, we analyze the inhibitory effect on global protein synthesis by nsp15 EndoU of α- and β-CoVs. This thesis thereby provides novel insights into nsp15 EndoU’s role in the infection with IBV but also other coronaviruses, which can promote the development of novel vaccines for IBV or novel anti-viral drugs for coronaviruses in general

Diallyl Trisulfide, the Antifungal Component of Garlic Essential Oil and the Bioactivity of Its Nanoemulsions Formed by Spontaneous Emulsification

The aim of this study was to evaluate the chemical compounds of garlic essential oil (EO), and determine the antifungal efficacy of garlic EO and its major components, diallyl trisulfide and its nanoemulsions against wood-rotting fungi, Trametes hirsuta and Laetiporus sulphureus. GC-MS analysis revealed that the major constituents of garlic EO were diallyl trisulfide (39.79%), diallyl disulfide (32.91%), and diallyl sulfide (7.02%). In antifungal activity, the IC50 value of garlic EO against T. hirsuta and L. sulphureus were 137.3 and 44.6 μg/mL, respectively. Results from the antifungal tests demonstrated that the three major constituents were shown to have good antifungal activity, in which, diallyl trisulfide was the most effective against T. hirsuta and L. sulphureus, with the IC50 values of 56.1 and 31.6 μg/mL, respectively. The diallyl trisulfide nanoemulsions showed high antifungal efficacy against the examined wood-rotting fungi, and as the amount of diallyl trisulfide in the lipid phase increases, the antifungal efficacy of the nanoemulsions increases. These results showed that the nanoemulsions and normal emulsion of diallyl trisulfide have potential to develop into a natural wood preservative