Analyzing state-dependent model–data comparison in multi-regime systems

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Computational Geosciences 15 (2011): 627-636, doi:10.1007/s10596-011-9229-3.An approach to analyze regime change in spatial time series data sets is followed and extended to jointly analyze a dynamical model depicting regime shift and observational data informing the same process. We analyze changes in the joint model-data regime and covariability within each regime. The method is applied to two observational data sets of equatorial sea surface temperature (TAO/TRITON array and satellite) and compared with the predicted data by the ECCO-JPL modeling system.Funding for this work was provided by Spanish National Program on Space, under contract ESP2005-06823-C05. A. Aretxabaleta has been additionally supported by a Juan de la Cierva grant of the Spanish Government. K. Smith was supported by NSF Grant DMS-0934653

Expectation-maximization analysis of spatial time series

© Author(s) 2007. This work is licensed under a Creative Commons License. The definitive version was published in Nonlinear Processes in Geophysics 14 (2007): 73-77, doi: 10.5194/npg-14-73-2007Expectation maximization (EM) is used to estimate the parameters of a Gaussian Mixture Model for spatial time series data. The method is presented as an alternative and complement to Empirical Orthogonal Function (EOF) analysis. The resulting weights, associating time points with component distributions, are used to distinguish physical regimes. The method is applied to equatorial Pacific sea surface temperature data from the TAO/TRITON mooring time series. Effectively, the EM algorithm partitions the time series into El Nino, La Nina and normal conditions. The EM method leads to a clearer interpretation of the variability associated with each regime than the basic EOF analysis.This work was supported by NSF grant DMS-0417845

Wind-induced, cross-frontal exchange on Georges Bank : a mechanism for early summer on-bank biological particle transport

Author Posting. © American Geophysical Union, 2003. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 108, C11 (2003): 8011, doi:10.1029/2002JC001358.Water exchange across the tidal-mixing front on the southern flank of Georges Bank (GB) is examined using a two-dimensional (2D) primitive equation ocean model. The model domain features a cross-frontal transect including a June 1999 hydrographic (CTD)/ADCP study made as part of the U.S. GLOBEC Northwest Atlantic/Georges Bank program. The model was initialized with temperature and salinity fields taken on the 15 June 1999 CTD section and run prognostically with tidal forcing, measured winds, and representative surface heat flux. The results show that fluctuations of wind plus tidal mixing can play the following essential role in the short-term transport of water and particles from the stratified region to the mixed region on GB in early summer, when stratification is just developing with a weak thermocline at a depth of about 10 m. First, a passing weather front drives a wind-induced on-bank Ekman transport of the upper part of the water column at the tidal-mixing front and associated particles in the surface mixed layer. Then, when the wind relaxes or changes direction, the water in the on-bank extension of the front (above the thermocline) mixes quickly through enhanced tidal motion in shallower depths of water. As a result, particles that are advected along the extended front stay in the previously well-mixed region of the bank. Surface heating tends to increase the strength of the thermocline and reduce the thickness of the surface mixed layer. This in turn accelerates the on-bank movement of the front under an easterly wind favorable for Ekman transport and thus enhances the on-bank, cross-frontal transport of particles. Since the wind-induced, cross-frontal on-bank transport of water can occur episodically during passages of meteorological fronts, these could produce a larger net cross-frontal flux than that produced by just tidal forcing on equivalent timescales. Therefore wind-induced processes can be important in the on-bank cross-frontal flux of copepods and other zooplankton species that exhibit shallow maxima in their vertical distributions over the southern flank of GB in early summer.This research was supported by the U.S. GLOBEC Northwest Atlantic/Georges Bank program through NOAA grants NA56RG0487, NA960P003, and NA960P005 to C. Chen, NOAA support to R. Schlitz, G. R. Lough, K. Smith, and J. Manning, and NSF grants OCE 96-32357, OCE 98-06379, and OCE 02-27679 to R. Beardsley

Model simulations of the Bay of Fundy Gyre : 2. Hindcasts for 2005–2007 reveal interannual variability in retentiveness

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C09005, doi:10.1029/2008JC004948.A persistent gyre at the mouth of the Bay of Fundy results from a combination of tidal rectification and buoyancy forcing. Here we assess recent interannual variability in the strength of the gyre using data assimilative model simulations. Realistic hindcast representations of the gyre are considered during cruises in 2005, 2006, and 2007. Assimilation of shipboard and moored acoustic Doppler current profiler velocities is used to improve the skill of the simulations, as quantified by comparison with nonassimilated drifter trajectories. Our hindcasts suggest a weakening of the gyre system during May 2005. Retention of simulated passive particles in the gyre during that period was highly reduced. A recovery of the dense water pool in the deep part of the basin by June 2006 resulted in a return to particle retention characteristics similar to climatology. Retention estimates reached a maximum during May 2007 (subsurface) and June–July 2007 (near surface). Interannual variability in the strength of the gyre was primarily modulated by the stratification of the dense water pool inside the Grand Manan Basin. These changes in stratification were associated with mixing conditions the preceding fall–winter and/or advectively driven modification of water mass properties.The preparation of this paper was supported by NSF grant OCE-0430724, NIEHS grant 1P50-ES01274201 (Woods Hole Center for Oceans and Human Health), andNOAAgrant NA06NOS4780245 (GOMTOX). Additional support was provided by NSF grant DMS-0417769

Model simulations of the Bay of Fundy Gyre : 1. Climatological results

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C10027, doi:10.1029/2007JC004480.The characteristics of a persistent gyre in the mouth of the Bay of Fundy are studied using model simulations. A set of climatological runs are conducted to evaluate the relative importance of the different forcing mechanisms affecting the gyre. The main mechanisms are tidal rectification and density-driven circulation. Stronger circulation of the gyre occurs during the later part of the stratified season (July–August and September–October). The density-driven flow around the gyre is set up by weak tidal mixing in the deep basin in the central Bay of Fundy and strong tidal mixing on the shallow flanks around Grand Manan Island and western Nova Scotia. Spring river discharge has an important influence on near-surface circulation but only a small effect when averaged over the entire water column. Retention of particles in the gyre is controlled by the residual tidal circulation, increased frontal retention during stratified periods, wind stress, and interactions with the adjacent circulation of the Gulf of Maine. Residence times longer than 30 days are predicted for particles released in the proximity of the gyre.The preparation of this paper was supported by NSF grant OCE-0430724 and NIEHS grant 1P50-ES01274201 (Woods Hole Center for Oceans and Human Health) and NOAA grant NA06NOS4780245 (GOMTOX). Additional support was provided by NSF grant DMS-0417769

Model initialization in a tidally energetic regime : a dynamically adjusted objective analysis

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Ocean Modelling 36 (2011): 219-227, doi:10.1016/j.ocemod.2011.01.001.A simple improvement to objective analysis of hydrographic data is proposed to eliminate spatial aliasing e ects in tidally energetic regions. The proposed method consists of the evaluation of anomalies from observations with respect to circulation model elds. The procedure is run iteratively to achieve convergence. The method is applied in the Bay of Fundy and compared with traditional objective analysis procedures and dynamically adjusted climatological elds. The hydrographic skill (di erence between observed and model temperature and salinity) of the dynamically adjusted objective analysis is signi cantly improved by reducing bias and correcting the vertical structure. Representation of the observed velocities is also improved. The resulting ow is consistent with the known circulation in the Bay.The preparation of this paper was supported by NSF/NIEHS grant OCE- 0430724 (Woods Hole Center for Oceans and Human Health) and NOAA grant NA06NOS4780245 (GOMTOX)

DNA Damage and Reactive Nitrogen Species are Barriers to Vibrio cholerae Colonization of the Infant Mouse Intestine

Ingested Vibrio cholerae pass through the stomach and colonize the small intestines of its host. Here, we show that V. cholerae requires at least two types of DNA repair systems to efficiently compete for colonization of the infant mouse intestine. These results show that V. cholerae experiences increased DNA damage in the murine gastrointestinal tract. Agreeing with this, we show that passage through the murine gut increases the mutation frequency of V. cholerae compared to liquid culture passage. Our genetic analysis identifies known and novel defense enzymes required for detoxifying reactive nitrogen species (but not reactive oxygen species) that are also required for V. cholerae to efficiently colonize the infant mouse intestine, pointing to reactive nitrogen species as the potential cause of DNA damage. We demonstrate that potential reactive nitrogen species deleterious for V. cholerae are not generated by host inducible nitric oxide synthase (iNOS) activity and instead may be derived from acidified nitrite in the stomach. Agreeing with this hypothesis, we show that strains deficient in DNA repair or reactive nitrogen species defense that are defective in intestinal colonization have decreased growth or increased mutation frequency in acidified nitrite containing media. Moreover, we demonstrate that neutralizing stomach acid rescues the colonization defect of the DNA repair and reactive nitrogen species defense defective mutants suggesting a common defense pathway for these mutants

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Plume Source Detection using a Process Query System

A Process Query System (PQS) has the capability of filtering large volumes of real time data originating from a field of networked Physical Sensors. Modern air quality monitoring techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy will eventually provide massively distributed real time contamination data at high fidelity. As large networks of these sensors are deployed, improved techniques of data retrieval and assimilation will be required. The case of detecting a diffusion event such as a hazardous chemical plume is considered. In this scenario, a plume model based on an Ensemble Kalman Filter (EnKF)is submitted to the PQS which manages multiple hypotheses explaining the current observations. The feasibility of such an application is demonstrated and results from preliminary simulations are presented

Multi-regime non-Gaussian data filling for incomplete ocean datasets

8 pages, 4 figures, 2 appendixA method is introduced for improved estimation of missing data that preserves the multi-regime characteristics of a dataset. The approach analyzes regime change in spatial time series by applying an Expectation-Maximization algorithm (an iterative procedure that finds the Maximum Likelihood Estimate of statistical model parameters) for the determination of a Gaussian Mixture Model (GMM). We estimate the GMM when only a linear noisy measurement of the underlying process is available. We demonstrate the validity of the method using an idealized dataset and also by applying the method to equatorial sea surface salinity observed by the TAO/TRITON array. A percentage of the total observations is systematically extracted and predicted using the method to allow for validation. Finally, the approach is applied to recently available remote sea surface salinity from the SMOS satellite in the Amazon River plume region. Areas of large noise levels (reduced signal-to-noise ratios) are considered as missing data and predicted with the proposed approach. The method interprets regime changes and provides reconstructions of missing information based on the mean and covariability within each regime. •Optimal estimation of missing data is conducted while preserving multi-regime data character.•Expectation-Maximization is used to separate the components of the date and interpolate missing data.•Validity of the method is demonstrated using idealized and realistic (TAO/TRITON in situ and SMOS satellite) datasets. © 2013 Elsevier B.V.This is a contribution to the SMOS-BEC. Funding for this work was provided by the Spanish National Program on Space, under contract ESP2005-06823-C05. A. L. Aretxabaleta has been additionally supported by a Juan de la Cierva grant fromthe Spanish Government. K. W. Smithwas supported by his wages at Lowe Energy DesignPeer Reviewe