Furin and the adaptive mutation of SARS-COV2: A computational framework

SARS-2 virus has reached its most harmful mutated form and has damaged the world's economy, integrity, health system and peace to a limit. An open problem is to address the release of antibodies after the infection and after getting the individuals vaccinated against the virus. The viral fusion process is linked with the furin enzyme and the adaptation is linked with the mutation, called D614G mutation. The cell-protein studies are extremely challenging. We have developed a mathematical model to address the process at the cell-protein level and the delay is linked with this biological process. Genetic algorithm is used to approximate the parametric values. The mathematical model proposed during this research consists of virus concentration, the infected cells count at different stages and the effect of interferon. To improve the understanding of this model of SARS-CoV2 infection process, the action of interferon (IFN) is quantified using a variable for the non-linear mathematical model, that is based on a degradation parameter gamma. This parameter is responsible for the delay in the dynamics of this viral action. We emphasize that this delay responds to the evasion by SARS-CoV2 via antagonizing IFN production, inhibiting IFN signaling and improving viral IFN resistance. We have provided videos to explain the modeling scheme

Modeling the crossover behavior of the bacterial infection with the COVID-19 epidemics

To explore the crossover linkage of the bacterial infections resulting from the viral infection, within the host body, a computational framework is developed. It analyzes the additional pathogenic effect of Streptococcus pneumonia, one of the bacteria that can trigger the super-infection mechanism in the COVID-19 syndrome and the physiological effects of innate immunity for the control or eradication of this bacterial infection. The computational framework, in a novel manner, takes into account the action of pro-inflammatory and anti-inflammatory cytokines in response to the function of macrophages. A hypothetical model is created and is transformed to a system of non-dimensional mathematical equations. The dynamics of three main parameters (macrophages sensitivity κ, sensitivity to cytokines η and bacterial sensitivity ϵ), analyzes a “threshold value” termed as the basic reproduction number R0 which is based on a sub-model of the inflammatory state. Piece-wise differentiation approach is used and dynamical analysis for the inflammatory response of macrophages is studied in detail. The results shows that the inflamatory response, with high probability in bacterial super-infection, is concomitant with the COVID-19 infection. The mechanism of action of the anti-inflammatory cytokines is discussed during this research and it is observed that these cytokines do not prevent inflammation chronic, but only reduce its level while increasing the activation threshold of macrophages. The results of the model quantifies the probable deficit of the biological mechanisms linked with the anti-inflammatory cytokines. The numerical results shows that for such mechanisms, a minimal action of the pathogens is strongly amplified, resulting in the “chronicity” of the inflammatory process.Taif University, Taif, Saudi Arabi

Forecasting the action of CAR-T cells against SARS-corona virus-II infection with branching process

The CAR-T cells are the genetically engineered T cells, designed to work specifically for the virus antigens (or other antigens, such as tumour specific antigens). The CAR-T cells work as the living drug and thus provides an adoptive immunotherapy strategy. The novel corona virus treatment and control designs are still under clinical trials. One of such techniques is the injection of CAR-T cells to fight against the COVID-19 infection. In this manuscript, the hypothesis is based on the CAR-T cells, that are suitably engineered towards SARS-2 viral antigen, by the N protein. The N protein binds to the SARS-2 viral RNA and is found in abundance in this virus, thus for the engineered cell research, this protein sequence is chosen as a potential target. The use of the sub-population of T-reg cells is also outlined. Mathematical modeling of such complex line of action can help to understand the dynamics. The modeling approach is inspired from the probabilistic rules, including the branching process, the Moran process and kinetic models. The Moran processes are well recognized in the fields of artificial intelligence and data science. The model depicts the infectious axis “virus—CAR-T cells—memory cells”. The theoretical analysis provides a positive therapeutic action; the delay in viral production may have a significant impact on the early stages of infection. Although it is necessary to carefully evaluate the possible side effects of therapy. This work introduces the possibility of hypothesizing an antiviral use by CAR-T cells

Computational model to explore the endocrine response to trastuzumab action in HER-2/neu positive breast cancer

Breast cancer is a very frequent type of cancer and much attention is paid to therapy with considerable efforts both in the pharmacological and clinical fields.The present work aims to create a non-linear dynamic model of action of the drug Trastuzumab against HER-2 + breast cancer, mainly considering its action of ADCP (antibody-dependent phagocytosis) killing of cancer cells. The model, while also considering the other therapeutic effects induced by Trastuzumab, shows how the action of this monoclonal antibody in the induction of ADCP through the action of macrophages, is strictly connected to the formation of a multi-complex “Trastuzumab -HER-2 - macrophage” that shows a prolonged action over time, responsible for the increase in the Overall Survivor (OS) parameter reported in various. The model shows the correlation between the various therapeutic effects and the killing action of cancer cells through the variation of the dynamic fluctuation of the representative ”c” parameter

Delayed Modeling Approach to Forecast the Periodic Behavior of SARS-2

The ongoing threat of Coronavirus is alarming. The key players of this virus are modeled mathematically during this research. The transmission rates are hypothesized, with the aid of epidemiological concepts and recent findings. The model reported is extended, by taking into account the delayed dynamics. Time delay reflects the fact that the dynamic behavior of transmission of the disease, at time t depends not only on the state at time t but also on the state in some period τ before time t. The research presented in this manuscript will not only help in understanding the current threat of pandemic (SARS-2), but will also contribute in making precautionary measures and developing control strategies.</jats:p

A CBCT based evaluation of root proximity of maxillary posterior teeth to sinus floor in a subset of Pakistani population

Abstract Objectives: To evaluate the vertical relationship of the roots of maxillary posterior teeth with maxillary sinus floorand its association with age, gender and bilateral jaw symmetry. Method: The cross-sectional study was conducted at a tertiary care hospital in Karachi from June to December 2018, and comprised patients who visited the dental clinics and underwent cone-beam computed tomography scans. The scans were evaluated in the axial, coronal and sagittal planes and roots were classified using Jungs classification for proximity to maxillary sinus floor. The distance between the sinus floor and the apices of maxillary posterior teeth was measured.  Data was analysed using SPSS 23. Results: There were 60 scans with 1066 roots. The most common maxillary tooth root in Type III group of Jung classification was the mesio-buccal root of the 2nd molar with the shortest mean distance of 0.44±3.05mm, followed by palatal roots of the 1st molar with the shortest mean distance of 1.58±4.01mm. The maxillary tooth root most frequent in Type I group was buccal root of 1st premolar with a mean distance of 8.15±6.65mm, and the 2nd premolar with a mean distance of 7.38±6.60mm. No significant difference was found in terms of gender and sides (p ?0.05). Conclusion: The most common root protruding in the sinus was found to be the mesio-buccal root of the 2nd molar, followed by palatal roots of the 1st molar. The most distant maxillary tooth root from the sinus was the buccal root of 1st and 2nd premolars. Continuous...</jats:p