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Publications about 'infections'
Articles in journal or book chapters
  1. Eduardo D. Sontag. An explicit formula for minimizing the infected peak in an SIR epidemic model when using a fixed number of complete lockdowns. medRxiv, 2021. Note: Submitted to a journal for peer review.[WWW] Keyword(s): epidemiology, COVID-19, COVID, systems biology.
    Abstract:
    A too-early start of NPIs (non-pharmaceutical interventions) such as social distancing may lead to high "second waves" of infections of COVID-19. This paper asks what should be the timing of a set of k complete-lockdowns of prespecified lengths (such as two weeks) so as to minimize the peak of the infective compartment. Perhaps surprisingly, it is possible to give an explicit and easily computable rule for when each lockdown should commence. Simulations are used to show that the rule remains fairly accurate even if lockdowns are not perfect.


  2. E.V. Nikolaev, A. Zloza, and E.D. Sontag. Immunobiochemical reconstruction of influenza lung infection - melanoma skin cancer interactions. Frontiers in Immunology, 10:Article 4, 2019. [PDF] Keyword(s): oncology, cancer, infections, immunology, checkpoint inhibition, systems biology.
    Abstract:
    Recent experimental results from the Zloza lab combined a mouse model of influenza A virus (IAV) infection (A/H1N1/PR8) and a highly aggressive model of infection-unrelated cancer, B16-F10 skin melanoma. This paper showed that acute influenza infection of the lung promotes distal melanoma growth in the dermis of the flank and leads to decreased host survival. Here, we proceed to ground the experimental observations in a mechanistic immunobiochemical model that incorporates the T cell receptor signaling pathway, various transcription factors, and a gene regulatory network (GRN). A core component of our model is a biochemical motif, which we call a Triple Incoherent Feed-Forward Loop (TIFFL), and which reflects known interactions between IRF4, Blimp-1, and Bcl-6. The different activity levels of the TIFFL components, as a function of the cognate antigen levels and the given inflammation context, manifest themselves in phenotypically distinct outcomes. Specifically, both the TIFFL reconstruction and quantitative estimates obtained from the model allowed us to formulate a hypothesis that it is the loss of the fundamental TIFFL-induced adaptation of the expression of PD-1 receptors on anti-melanoma CD8+ T cells that constitutes the essence of the previously unrecognized immunologic factor that promotes the experimentally observed distal tumor growth in the presence of acute non-ocogenic infection. We therefore hope that this work can further highlight the importance of adaptive mechanisms by which immune functions contribute to the balance between self and non-self immune tolerance, adaptive resistance, and the strength of TCR-induced activation, thus contributing to the understanding of a broader complexity of fundamental interactions between pathogens and tumors.


  3. K. Wood, S. Nishida, E.D. Sontag, and P. Cluzel. Mechanism-independent method for predicting response to multiple drug exposure in bacteria. Proc Natl Acad Sci USA, 109:12254-12259, 2012. [PDF] Keyword(s): systems biology, drug interactions.
    Abstract:
    Drugs are commonly used in combinations larger than two for treating bacterial infections. It is generally impossible to infer directly from the effects of individual drugs the net effect of a multi-drug combination. This paper describes an empirically derived mechanism-independent method for predicting the microbial growth response to combinations of more than two drugs, experimentally tested on both gram-negative (Escherichia coli) and grampositive (Staphylococcus aureus) bacteria. The method shows that for a wide range of drugs, the bacterial responses to drug pairs are sufficient to infer the effects of larger drug combinations, and provides a simple formula for the prediction.



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Last modified: Thu Jun 3 23:14:08 2021
Author: sontag.


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