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

L'interessamento del sistema linfatico nell'amiloidosi cardiaca da catene leggere: un possibile nuovo aspetto della patogenesi della malattia

L'amiloidosi a catene leggere (AL) è causata dalla deposizione, nell'interstizio cardiaco, di frammenti di anticorpi, le catene leggere. Ciò si verifica a causa della produzione incontrollata di immunoglobuline da parte di cellule che si trovano nel midollo osseo, le plasmacellule, nel corso di malattie neoplastiche delle stesse, le c.d. discrasie plasmacellulari. Tale tipologia di amiloidosi interessa sovente il cuore (nel 75% dei pazienti) con prognosi di solito infausta. La presente dissertazione, dopo una panoramica sull’amiloide e sulla sua formazione, prende in particolare considerazione l’interessamento del sistema linfatico cardiaco in questa patologia, ipotizzando che esso rappresenti un nuovo possibile aspetto della sua patogenesi. È infatti verosimile che la formazione della proteina amiloide, nel caso di amiloidosi AL, non solo riesca a compromettere direttamente l’attività dei miocardiociti, ma anche il flusso linfatico nel sistema linfatico cardiaco, costituendo un ipotetico nuovo meccanismo di danno. È possibile che in generale, nell'amiloidosi, proprio il sistema linfatico stesso rivesta un ruolo importante nel riassorbimento della proteina amiloide, e che il deposito di tale materiale patologico infici tale processo; questo evento può avvenire anche a carico del cuore, comportando una sorta di decompensazione dell’omeostasi linfatica dell'organo, alterando così il suo normale funzionamento. In virtù delle conoscenze relative al ruolo del sistema linfatico cardiaco nella risposta al danno miocardico, nel presente studio si ipotizza che la compromissione del sistema linfatico cardiaco possa contribuire al concomitante peggioramento della funzione cardiaca nell'amiloidosi AL, per una disregolazione dei meccanismi di controllo dell'infiammazione e per la mancata o abnorme linfangiogenesi, entrambi aspetti che potrebbero compromettere i meccanismi di omeostasi cellulare necessari al mantenimento della funzionalità dell'organo. Light chain amyloidosis (AL) is caused by the deposition, in the heart interstitium, of fragments of antibodies, the light chains. This occurs due to the uncontrolled production of immunoglobulins by cells found in the bone marrow, the plasma cells, in the course of neoplastic diseases of the same, the so-called plasma cell dyscrasias. This type of amyloidosis often affects the heart (in 75% of patients) with usually poor prognosis. This dissertation, after an overview of amyloid and its formation, takes into particular consideration the involvement of the cardiac lymphatic system in this pathology, assuming that it represents a new possible aspect of its pathogenesis. It is in fact likely that the formation of the amyloid protein, in the case of AL amyloidosis, not only manages to directly compromise the activity of myocardiocytes, but also the lymphatic flow in the cardiac lymphatic system, constituting a hypothetical new damage mechanism. It is possible that in general, in amyloidosis, the lymphatic system itself plays an important role in the reabsorption of the amyloid protein, and that the deposition of this pathological material affects this process; this event can also occur in the heart, leading to a sort of decompensation of the organ's lymphatic homeostasis, thus altering its normal functioning. Based on the knowledge about the role of the cardiac lymphatic system in the response to myocardial damage, in the present study it is hypothesized that the impairment of the cardiac lymphatic system may contribute to the concomitant worsening of cardiac function in AL amyloidosis, due to a dysregulation of the control mechanisms of inflammation and the lack of or abnormal lymphangiogenesis, both aspects that could compromise the mechanisms of cellular homeostasis necessary for maintaining the function of the organ

Contributo del telerilevamento da satellite alla comprensione dei fenomeni idrologici del fiume Congo

project Geoland2. Congo basin is one of the target area where NARMA has to contribute to the development of AMESD/CEMAC services in support to management of water resources focusing on environmental aspects of watersheds. In this contest and to better understand dynamics that occur in the watershed, an analysis has been conducted on the relation between precipitation, river discharge and vegetation dynamics by exploiting available time series of Earth Observation data. Rainfall dynamics has been described using FEWS-NET RFE estimations, river discharge has been monitored using ENVISAT radar altimeter data provided by LEGOS laboratory and vegetation dynamics have been examined through vegetation indices available from long term series of SPOT¿VGT data. The comparison between river discharge measured at Bangui (Central African Republic), gauging station and radar altimeter virtual station data demonstrated that these data can be used to estimate river discharge. Results on Uelè basin showed that a strong positive correlation is obtained between rain data and river discharge only at the end of the vegetation season when plants have reduced water demand for evapotranspiration and less intercept rain. Trend analysis on the considered time windows are provided and the contribution of these finding for river water alert monitoring system is discussed.JRC.DDG.H.3-Global environement monitorin

Analysis of earth observation time series to investigate the relation between rainfall, vegetation dynamic and streamflow in the Uele' basin (Central African Republic)

The hydrology of tropical forests play a key role in watershed processes such as soil erosion, streamflow and ground water recharge. However, tropical forests of Africa are least investigated due to the poor network for data acquisition. Earth Observations can fill this gap by providing consistent time series of data. We analyzed trends of rainfall, vegetation index and river water levels derived from satellite data for the Uele sub-basin and we pointed out that rainfall and river water levels are positively correlated only during the dry season when vegetation activities is low. The unexpected low correlation during the season of highest precipitations is due to the role of vegetation, which is characterized by a significant seasonality also in evergreen tropical forests. These results underline the importance of modeling the role of canopy in the interception and evapotranspiration of the available precipitation in order to provide reliable information on stream flow dynamics. Index Terms— River hydrology, Earth Observations, RFE, NDWI, radar altimeterJRC.H.3-Global environement monitorin

Identification of environmental anomaly hot spots in West Africa from time series of NDVI and rainfall

Studies of the impact of human activity on the vegetation dynamics in the Sahelian belt of Africa have been recently re-invigorated by new scientific findings that highlighted the primary role of climate in the drought crises of the 70-80s. Time series of satellite observations allowed identifying regreening of the Sahelian belt that indicate no noteworthy human effect on vegetation dynamics at sub continental scale from 80s to late 90s. However, several regional/local crises related to natural resources occurred in the last decades despite the re-greening thus underlying that more detailed studies are needed. This study contributes to the understanding of climate and human impacts on the vegetation in the Sahelian region in the last decade (1998-2010). The use of time-series of SPOT-VGT NDVI and FEWS-RFE rainfall estimates allowed us to analyze vegetation and rainfall trends and to identify local anomalous situations. Trend analysis has been conducted to map a) areas where vegetation has been significantly decreasing or increasing due to changes in rainfall patterns and b) anomalous hot spot zones where vegetation dynamics could not be fully explained by changes of rainfall patterns. Multi-temporal analysis of Landsat images allows us to evaluate the reliability of the identified trends and to provide an interpretation of some example hot spots. The frequency distribution of the anomalous situations among the land cover class of the GlobCover map shows that, at the regional scale, environmental degradation occurs mainly in herbaceous vegetation covers where pastoral and cropping practices are often critical due to low and very unpredictable rainfall. The results of this study show that even if a general positive re-greening trend due to increased rainfall is evident for the entire Sahel, some local anomalous hot spots exist and can be explained by human factors such as population growth whose level reaches the ecosystem carrying capacity as well as population displacement leading to vegetation recovery.JRC.H.5-Land Resources Managemen

Modeling and simulation of the "IL-36 cytokine" and CAR-T cells interplay in cancer onset

Background: CAR-T cells are chimeric antigen receptor (CAR)-T cells; they are target-specific engineered cells on tumor cells and produce T cell-mediated antitumor responses. CAR-T cell therapy is the "first-line" therapy in immunotherapy for the treatment of highly clonal neoplasms such as lymphoma and leukemia. This adoptive therapy is currently being studied and tested even in the case of solid tumors such as osteosarcoma since, precisely for this type of tumor, the use of immune checkpoint inhibitors remained disappointing. Although CAR-T is a promising therapeutic technique, there are therapeutic limits linked to the persistence of these cells and to the tumor's immune escape. CAR-T cell engineering techniques are allowed to express interleukin IL-36, and seem to be much more efficient in antitumoral action. IL-36 is involved in the long-term antitumor action, allowing CAR-T cells to be more efficient in their antitumor action due to a "cross-talk" action between the "IL-36/dendritic cells" axis and the adaptive immunity. Methods: This analysis makes the model useful for evaluating cell dynamics in the case of tumor relapses or specific understanding of the action of CAR-T cells in certain types of tumor. The model proposed here seeks to quantify the action and interaction between the three fundamental elements of this antitumor activity induced by this type of adoptive immunotherapy: IL-36, "armored" CAR-T cells (i.e., engineered to produce IL-36) and the tumor cell population, focusing exclusively on the action of this interleukin and on the antitumor consequences of the so modified CAR-T cells. Mathematical model was developed and numerical simulations were carried out during this research. The development of the model with stability analysis by conditions of Routh-Hurwitz shows how IL-36 makes CAR-T cells more efficient and persistent over time and more effective in the antitumoral treatment, making therapy more effective against the "solid tumor". Findings: Primary malignant bone tumors are quite rare (about 3% of all tumors) and the vast majority consist of osteosarcomas and Ewing's sarcoma and, approximately, the 20% of patients undergo metastasis situations that is the most likely cause of death. Interpretation: In bone tumor like osteosarcoma, there is a variation of the cellular mechanical characteristics that can influence the efficacy of chemotherapy and increase the metastatic capacity; an approach related to adoptive immunotherapy with CAR-T cells may be a possible solution because this type of therapy is not influenced by the biomechanics of cancer cells which show peculiar characteristics

The upper section shows high resolution LC maps (blue: Water; green: vegetation; orange: bare soil; white: clouds) from Landsat analysis and water maps from MODIS for VIS/SVIR indices using global thresholds at the four test sites.

<p>The lower section shows the performance of VIS/SWIR, VIS/NIR, NIR/SWIR indices and the combined B2B6-EVI index in the Omission/Commission Error space. Pareto boundaries in the Omission/Commission Error space for each site are provided.</p