A Koopman operator-based prediction algorithm and its application to COVID-19 pandemic and influenza cases.

Future state prediction for nonlinear dynamical systems is a challenging task. Classical prediction theory is based on a, typically long, sequence of prior observations and is rooted in assumptions on statistical stationarity of the underlying stochastic process. These algorithms have trouble predicting chaotic dynamics, "Black Swans" (events which have never previously been seen in the observed data), or systems where the underlying driving process fundamentally changes. In this paper we develop (1) a global and local prediction algorithm that can handle these types of systems, (2) a method of switching between local and global prediction, and (3) a retouching method that tracks what predictions would have been if the underlying dynamics had not changed and uses these predictions when the underlying process reverts back to the original dynamics. The methodology is rooted in Koopman operator theory from dynamical systems. An advantage is that it is model-free, purely data-driven and adapts organically to changes in the system. While we showcase the algorithms on predicting the number of infected cases for COVID-19 and influenza cases, we emphasize that this is a general prediction methodology that has applications far outside of epidemiology.

Temporal variations analyses and predictive modeling of microbiological seawater quality.

Bathing water quality is a major public health issue, especially for tourism-oriented regions. Currently used methods within EU allow at least a 2.2 day period for obtaining the analytical results, making outdated the information forwarded to the public. Obtained results and beach assessment are influenced by the temporal and spatial characteristics of sample collection, and numerous environmental parameters, as well as by differences of official water standards. This paper examines the temporal variation of microbiological parameters during the day, as well as the influence of the sampling hour, on decision processes in the management of the beach. Apart from the fecal indicators stipulated by the EU Bathing Water Directive (E. coli and enterococci), additional fecal (C. perfringens) and non-fecal (S. aureus and P. aeriginosa) parameters were analyzed. Moreover, the effects of applying different evaluation criteria (national, EU and U.S. EPA) to beach ranking were studied, and the most common reasons for exceeding water-quality standards were investigated. In order to upgrade routine monitoring, a predictive statistical model was developed. The highest concentrations of fecal indicators were recorded early in the morning (6 AM) due to the lack of solar radiation during the night period. When compared to enterococci, E. coli criteria appears to be more stringent for the detection of fecal pollution. In comparison to EU and U.S. EPA criteria, Croatian national evaluation criteria provide stricter public health standards. Solar radiation and precipitation were the predominant environmental parameters affecting beach water quality, and these parameters were included in the predictive model setup. Predictive models revealed great potential for the monitoring of recreational water bodies, and with further development can become a useful tool for the improvement of public health protection.

Quantitative Analysis of Endocytic Recycling of Membrane Proteins by Monoclonal Antibody-Based Recycling Assays.

In this report, we present an analysis of several recycling protocols based on labeling of membrane proteins with specific monoclonal antibodies (mAbs). We analyzed recycling of membrane proteins that are internalized by clathrin-dependent endocytosis, represented by the transferrin receptor, and by clathrin-independent endocytosis, represented by the Major Histocompatibility Class I molecules. Cell surface membrane proteins were labeled with mAbs and recycling of mAb:protein complexes was determined by several approaches. Our study demonstrates that direct and indirect detection of recycled mAb:protein complexes at the cell surface underestimate the recycling pool, especially for clathrin-dependent membrane proteins that are rapidly reinternalized after recycling. Recycling protocols based on the capture of recycled mAb:protein complexes require the use of the Alexa Fluor 488 conjugated secondary antibodies or FITC-conjugated secondary antibodies in combination with inhibitors of endosomal acidification and degradation. Finally, protocols based on the capture of recycled proteins that are labeled with Alexa Fluor 488 conjugated primary antibodies and quenching of fluorescence by the anti-Alexa Fluor 488 displayed the same quantitative assessment of recycling as the antibody-capture protocols. J. Cell. Physiol. 232: 463-476, 2017. © 2016 Wiley Periodicals, Inc.

Late Endosomal Recycling of Open MHC-I Conformers.

With an increasing number of endosomal cargo molecules studied, it is becoming clear that endocytic routes are diverse, and the cell uses more pathways to adjust expression of cell surface proteins. Intracellular itinerary of integral membrane proteins that avoid the early endosomal recycling route is not enough studied. Therefore, we studied endocytic trafficking of empty Ld (eLd ) molecules, an open form of murine MHC-I allele, in fibroblast-like cells. Pulse labeling of cell surface eLd with mAbs and internalization kinetics suggest two steps of endosomal recycling: rapid and late. The same kinetics was also observed for human open MHC-I conformers. Kinetic modeling, using in-house developed software for multicompartment analysis, colocalization studies and established protocols for enriched labeling of the late endosomal (LE) pool of eLd demonstrated that the late step of recycling occurs from an LE compartment. Although the majority of eLd distributed into pre-degradative multivesicular bodies (MVBs), these LE subsets were not a source for eLd recycling. The LE recycling of eLd did not require Rab7 membrane domains, as demonstrated by Rab7-silencing, but required vectorial LE motility, suggesting that LE recycling occurs from dynamic tubulovesicular LE domains prior segregation of eLd in MVBs. Thus, our study indicates that LE system should not be simply considered as a feeder for loading of the degradative tract of the cell but also as a feeder for loading of the plasma membrane and thereby contribute to the maintenance of homeostasis of plasma membrane proteins. J. Cell. Physiol. 232: 872-887, 2017. © 2016 Wiley Periodicals, Inc.

Dynamic autoinoculation and the microbial ecology of a deep water hydrocarbon irruption.

The irruption of gas and oil into the Gulf of Mexico during the Deepwater Horizon event fed a deep sea bacterial bloom that consumed hydrocarbons in the affected waters, formed a regional oxygen anomaly, and altered the microbiology of the region. In this work, we develop a coupled physical-metabolic model to assess the impact of mixing processes on these deep ocean bacterial communities and their capacity for hydrocarbon and oxygen use. We find that observed biodegradation patterns are well-described by exponential growth of bacteria from seed populations present at low abundance and that current oscillation and mixing processes played a critical role in distributing hydrocarbons and associated bacterial blooms within the northeast Gulf of Mexico. Mixing processes also accelerated hydrocarbon degradation through an autoinoculation effect, where water masses, in which the hydrocarbon irruption had caused blooms, later returned to the spill site with hydrocarbon-degrading bacteria persisting at elevated abundance. Interestingly, although the initial irruption of hydrocarbons fed successive blooms of different bacterial types, subsequent irruptions promoted consistency in the structure of the bacterial community. These results highlight an impact of mixing and circulation processes on biodegradation activity of bacteria during the Deepwater Horizon event and suggest an important role for mixing processes in the microbial ecology of deep ocean environments.