Resonant activation: a strategy against bacterial persistence

A bacterial colony may develop a small number of cells genetically identical to, but phenotypically different from other normally growing bacteria. These so-called persister cells keep themselves in a dormant state and thus are insensitive to antibiotic treatment, resulting in serious problems of drug resistance. In this paper, we proposed a novel strategy to "kill" persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics. The strategy is based on resonant activation (RA), a well-studied phenomenon in physics where the internal noise of a system can constructively facilitate fast and synchronized barrier crossings. Through stochastic Gilliespie simulation with a generic toggle switch model, we demonstrated that RA exists in the phenotypic switching of a single bacterium. Further, by coupling single cell level and population level simulations, we showed that with RA, one can greatly reduce the time and total amount of antibiotics needed to sterilize a bacterial population. We suggest that resonant activation is a general phenomenon in phenotypic transition, and can find other applications such as cancer therapy.Comment: 21 pages, 12 figures, submitte

Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

We compare calcium ion signaling ($\mathrm {Ca}^{2+}$) between two exposures; the data are present as movies, or, more prosaically, time series of images. This paper describes novel uses of singular value decompositions (SVD) and weighted versions of them (WSVD) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses on the behavior of individual cells across time, and thus, the cells need to be segmented in an automated manner. Second, the cells themselves have 100$+$ pixels, so that they form 100$+$ curves measured over time, so that data compression is required to extract the features of these curves. Third, some of the pixels in some of the cells are subject to image saturation due to bit depth limits, and this saturation needs to be accounted for if one is to normalize the images in a reasonably unbiased manner. Finally, the $\mathrm {Ca}^{2+}$ signals have oscillations or waves that vary with time and these signals need to be extracted. Thus, our aim is to show how to use multiple weighted and standard singular value decompositions to detect, extract and clarify the $\mathrm {Ca}^{2+}$ signals. Our signal extraction methods then lead to simple although finely focused statistical methods to compare $\mathrm {Ca}^{2+}$ signals across experimental conditions.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS253 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Nondestructive Evaluation of Modulus of Elasticity of Southern Pine LVL: Effect of Veneer Grade and Relative Humidity

Nondestructive testing (NDT) methods, stress-wave propagation, and transverse vibration were used to evaluate the modulus of elasticity (MOE) of laminated veneer lumber (LVL). Five types of LVL, fabricated with southern pine veneers of B. C, and D grades and liquid phenolic formaldehyde adhesive, were tested flatwise at environmental conditions of 65% and 95% relative humidity (RH) and 75°F (23.9°) to examine the influence of veneer grade and RH on some nondestructive mechanical properties of LVL. All LVLs, 1.5 in. (3.81 cm) thick X 3.5 in. (8.89 cm) high X 96 in. (243.84 cm) long, consisted of 13 plies of southern pine veneer, and their structural designs were: (I) all B grade veneers, (II) 2 plies of B grade veneer on both faces and all C grade veneers in the core plies, (III) 2 plies of B grade veneer on both faces and all D grade veneer in the core plies, (IV) all C grade veneers, and (V) all D grade veneers. Results indicated that MOE of LVL predicted by NDT was influenced by the veneer grade, and specimens fabricated with better grade veneers showed a higher value of MOE. A significant decrease in the MOE determined by both NDT methods was found when RH increased from 65% to 95% at 23.9° (75°F). The MOE measured by the stress-wave method was found to be more sensitive to the RH change than that determined by the transverse-vibration method. A lognormal distribution accurately described the distributions of MOEs determined by both nondestructive methods at both RH levels. As expected, a significant increase in moisture content (MC) in the LVL resulted from increasing RH levels. However, changes in densities of the tested materials due to the RH changes were found to be smaller. Results also indicated that regardless of the RH level. MOE determined from the stress-wave test was consistently higher than that obtained from the transverse-vibration test. For comparison. the results of tests on southern pine No. 1 and No. 2 grade lumber, commonly used in light-frame construction, are also presented. Analysis of the correlation between the static bending and NDT MOEs was made and results suggested that edgewise static bending MOE of LVL can be predicted with reasonable accuracy by the stress-wave testing. Good correlations were not observed between the edgewise static bending MOE and the nondestructive MOE evaluated by flatwise transverse vibration. However, excellent correlations between static bending and both NDT MOEs were observed in southern pine dimension lumber. Correlations between the MOEs evaluated by both nondestructive methods were found to be fair for LVL specimens

An unstructured-grid, finite-volume sea ice model : development, validation, and application

Author Posting. © American Geophysical Union, 2011. 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 116 (2011): C00D04, doi:10.1029/2010JC006688.A sea ice model was developed by converting the Community Ice Code (CICE) into an unstructured-grid, finite-volume version (named UG-CICE). The governing equations were discretized with flux forms over control volumes in the computational domain configured with nonoverlapped triangular meshes in the horizontal and solved using a second-order accurate finite-volume solver. Implementing UG-CICE into the Arctic Ocean finite-volume community ocean model provides a new unstructured-grid, MPI-parallelized model system to resolve the ice-ocean interaction dynamics that frequently occur over complex irregular coastal geometries and steep bottom slopes. UG-CICE was first validated for three benchmark test problems to ensure its capability of repeating the ice dynamics features found in CICE and then for sea ice simulation in the Arctic Ocean under climatologic forcing conditions. The model-data comparison results demonstrate that UG-CICE is robust enough to simulate the seasonal variability of the sea ice concentration, ice coverage, and ice drifting in the Arctic Ocean and adjacent coastal regions.This work was supported by the NSF Arctic Program for projects with grant numbers of ARC0712903, ARC0732084, and ARC0804029. The Arctic Ocean Model Intercomparison Project (AOMIP) has provided an important guidance for model improvements and ocean studies under coordinated experiments activities. We would like to thank AOMIP PI Proshutinsky for his valuable suggestions and comments on the ice dynamics. His contribution is supported by ARC0800400 and ARC0712848. The development of FVCOM was supported by the Massachusetts Marine Fisheries Institute NOAA grants DOC/NOAA/ NA04NMF4720332 and DOC/NOAA/NA05NMF4721131; the NSF Ocean Science Program for projects of OCE‐0234545, OCE‐0227679, OCE‐ 0606928, OCE‐0712903, OCE‐0726851, and OCE‐0814505; MIT Sea Grant funds (2006‐RC‐103 and 2010‐R/RC‐116); and NOAA NERACOOS Program for the UMASS team. G. Gao was also supported by the Chinese NSF Arctic Ocean grant under contract 40476007. C. Chen’s contribution was also supported by Shanghai Ocean University International Cooperation Program (A‐2302‐10‐0003), the Program of Science and Technology Commission of Shanghai Municipality (09320503700), the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50702), and Zhi jiang Scholar and 111 project funds of the State Key Laboratory for Estuarine and Coastal Research, East China Normal University (ECNU)

Biophysics at the coffee shop: lessons learned working with George Oster

Over the past 50 years, the use of mathematical models, derived from physical reasoning, to describe molecular and cellular systems has evolved from an art of the few to a cornerstone of biological inquiry. George Oster stood out as a pioneer of this paradigm shift from descriptive to quantitative biology not only through his numerous research accomplishments, but also through the many students and postdocs he mentored over his long career. Those of us fortunate enough to have worked with George agree that his sharp intellect, physical intuition and passion for scientific inquiry not only inspired us as scientists but also greatly influenced the way we conduct research. We would like to share a few important lessons we learned from George in honor of his memory and with the hope that they may inspire future generations of scientists.Comment: 22 pages, 3 figures, accepted in Molecular Biology of the Cel

A dike–groyne algorithm in a terrain-following coordinate ocean model (FVCOM) : development, validation and application

Author Posting. © The Author(s), 2012. 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 47 (2012): 26-40, doi:10.1016/j.ocemod.2012.01.006.A dike-groyne module is developed and implemented into the unstructured-grid, three dimensional primitive equation Finite-Volume Coastal Ocean Model (FVCOM) for the study of the hydrodynamics around human-made construction in the coastal area. The unstructured-grid finite-volume flux discrete algorithm makes this module capable of realistically including narrow-width dikes and groynes with free exchange in the upper column and solid blocking in the lower column in a terrain-following coordinate system. This algorithm used in the module is validated for idealized cases with emerged and/or submerged dikes and a coastal seawall where either analytical solutions or laboratory experiments are available for comparison. As an example, this module is applied to the Changjiang Estuary where a dike-groyne structure was constructed in the Deep Waterway channel in the inner shelf of the East China Sea (ECS). Driven by the same forcing under given initial and boundary conditions, a comparison was made for model-predicted flow and salinity via observations between dike-groyne and bed-conforming slope algorithms. The results show that with realistic resolution of water transport above and below the dike-groyne structures, the new method provides more accurate results. FVCOM with this MPI-architecture parallelized dike-groyne module provides a new tool for ocean engineering and inundation applications in coastal regions with dike, seawall and/or dam structures.J. Ge and P. Ding have been supported by the Fund for Creative Research Groups of NSFC (No. 41021064), the PhD Program Scholarship Fund (2009010) of East China Normal University (ECNU), and the State Scholarship Fund from China Scholarship Council. C. Chen, J. Qi and R. C. Beardsley have been funded by the Northeast Regional Association of Coastal Ocean Observing Systems (NERACOOS), the IOOS/SURA Super-Regional Coastal Modeling Testbed, MIT Sea Grant NA06OAR4170019 and 571000271, and NSF grants OCE0606928, OCE0712903, OCE0732084, OCE0726851, OCE0814505, and OCE0804029

Seasonal and interannual variability of the Arctic sea ice : a comparison between AO-FVCOM and observations

Author Posting. © American Geophysical Union, 2016. 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: Oceans 121 (2016): 8320–8350, doi:10.1002/2016JC011841.A high-resolution (up to 2 km), unstructured-grid, fully ice-sea coupled Arctic Ocean Finite-Volume Community Ocean Model (AO-FVCOM) was used to simulate the sea ice in the Arctic over the period 1978–2014. The spatial-varying horizontal model resolution was designed to better resolve both topographic and baroclinic dynamics scales over the Arctic slope and narrow straits. The model-simulated sea ice was in good agreement with available observed sea ice extent, concentration, drift velocity and thickness, not only in seasonal and interannual variability but also in spatial distribution. Compared with six other Arctic Ocean models (ECCO2, GSFC, INMOM, ORCA, NAME, and UW), the AO-FVCOM-simulated ice thickness showed a higher mean correlation coefficient of ∼0.63 and a smaller residual with observations. Model-produced ice drift speed and direction errors varied with wind speed: the speed and direction errors increased and decreased as the wind speed increased, respectively. Efforts were made to examine the influences of parameterizations of air-ice external and ice-water interfacial stresses on the model-produced bias. The ice drift direction was more sensitive to air-ice drag coefficients and turning angles than the ice drift speed. Increasing or decreasing either 10% in water-ice drag coefficient or 10° in water-ice turning angle did not show a significant influence on the ice drift velocity simulation results although the sea ice drift speed was more sensitive to these two parameters than the sea ice drift direction. Using the COARE 4.0-derived parameterization of air-water drag coefficient for wind stress did not significantly influence the ice drift velocity simulation.This work was supported by NSF grants OCE-1203393 for the UMASSD team and PLR-1203643 for R. C. Beardsley.2017-05-2

Identifying network communities with a high resolution

Community structure is an important property of complex networks. An automatic discovery of such structure is a fundamental task in many disciplines, including sociology, biology, engineering, and computer science. Recently, several community discovery algorithms have been proposed based on the optimization of a quantity called modularity (Q). However, the problem of modularity optimization is NP-hard, and the existing approaches often suffer from prohibitively long running time or poor quality. Furthermore, it has been recently pointed out that algorithms based on optimizing Q will have a resolution limit, i.e., communities below a certain scale may not be detected. In this research, we first propose an efficient heuristic algorithm, Qcut, which combines spectral graph partitioning and local search to optimize Q. Using both synthetic and real networks, we show that Qcut can find higher modularities and is more scalable than the existing algorithms. Furthermore, using Qcut as an essential component, we propose a recursive algorithm, HQcut, to solve the resolution limit problem. We show that HQcut can successfully detect communities at a much finer scale and with a higher accuracy than the existing algorithms. Finally, we apply Qcut and HQcut to study a protein-protein interaction network, and show that the combination of the two algorithms can reveal interesting biological results that may be otherwise undetectable.Comment: 14 pages, 5 figures. 1 supplemental file at http://cic.cs.wustl.edu/qcut/supplemental.pd

Impact of current-wave interaction on storm surge simulation : a case study for Hurricane Bob

Author Posting. © American Geophysical Union, 2013. 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: Oceans 118 (2013): 2685–2701, doi:10.1002/jgrc.20207.Hurricane Bob moved up the U.S. east coast and crossed over southern New England and the Gulf of Maine [with peak marine winds up to 54 m/s (100 mph)] on 19–20 August 1991, causing significant damage along the coast and shelf. A 3-D fully wave-current-coupled finite-volume community ocean model system was developed and applied to simulate and examine the coastal ocean responses to Hurricane Bob. Results from process study-oriented experiments showed that the impact of wave-current interaction on surge elevation varied in space and time, more significant over the shelf than inside the inner bays. While sea level change along the coast was mainly driven by the water flux controlled by barotropic dynamics and the vertically integrated highest water transports were essentially the same for cases with and without water stratification, the hurricane-induced wave-current interaction could generate strong vertical current shear in the stratified areas, leading to a strong offshore transport near the bottom and vertical turbulent mixing over the continental shelf. Stratification could also result in a significant difference of water currents around islands where the water is not vertically well mixed.This work was supported by the MIT Sea Grant College Program through grant 2012-R/RC-127 and the NOAA NERACOOS Program funds for NECOFS. The development of the FVCOM system has been supported by the NSF Ocean Sciences Division through grants OCE-0234545, OCE-0227679, OCE-0606928, and OCE- 0712903 and the NSF Office of Polar Programs-Arctic Sciences Division through grants ARC0712903, ARC0732084, ARC0804029, and ARC1203393. C.C.’s contribution was also supported by Shanghai Ocean University International Cooperation Program (A-2302-11-0003), the Program of Science and Technology Commission of Shanghai Municipality (09320503700), and the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50702).2013-11-3