‘Domino’ systems biology and the ‘A’ of ATP

AbstractWe develop a strategic ‘domino’ approach that starts with one key feature of cell function and the main process providing for it, and then adds additional processes and components only as necessary to explain provoked experimental observations. The approach is here applied to the energy metabolism of yeast in a glucose limited chemostat, subjected to a sudden increase in glucose. The puzzles addressed include (i) the lack of increase in Adenosine triphosphate (ATP) upon glucose addition, (ii) the lack of increase in Adenosine diphosphate (ADP) when ATP is hydrolyzed, and (iii) the rapid disappearance of the ‘A’ (adenine) moiety of ATP. Neither the incorporation of nucleotides into new biomass, nor steady de novo synthesis of Adenosine monophosphate (AMP) explains. Cycling of the ‘A’ moiety accelerates when the cell's energy state is endangered, another essential domino among the seven required for understanding of the experimental observations. This new domino analysis shows how strategic experimental design and observations in tandem with theory and modeling may identify and resolve important paradoxes. It also highlights the hitherto unexpected role of the ‘A’ component of ATP

Experimental Metrics for Identifying Origins of Combustion Variability during Spark-Assisted Compression Ignition

Spark-assisted compression ignition, SACI, can be used to control the combustion phasing of compression-ignition gasoline engines. However, implementation of this technique can be confounded by cyclic variability. The purpose of this paper is to define experimental metrics that describe the SACI process and to demonstrate the use of these metrics for identifying the source(s) of cyclic variability during the SACI process. This study focused on a light load condition (7 mg/cycle, 200 kPa i.m.e.p.), where spray-guided direct fuel injection with spark ignition and an exhaust-rebreathing strategy was employed to achieve flame propagation, which led to compression ignition. This study employed a combination of measurements including pressure-based heat-release analysis, spark-discharge voltage/current measurements, and cycle-resolved combustion imaging. Based on these measurements, four distinct combustion periods were identified; namely, the spark discharge, the early kernel growth (EKG), flame propagation, and the compression ignition periods. Metrics were defined to characterize each period and used to identify the contribution of each period to the cyclic variability of the main heat release. For the light load condition studied here, the EKG period had the largest effect on the crank angle (CA) position of 50 per cent mass burned, CA50. The spark-discharge event may affect CA50 indirectly through its influence on EKG. However, this could not be definitively assessed here since the camera was incapable of recording both the spark-discharge event and the flame images during cycles of the same tests.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86770/1/Sick18.pd

3D modelling of angiogenesis and vascular tumour growth

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute

An Experimental and Simulation Study of Early Flame Development in a Homogeneous-Charge Spark-Ignition Engine

An integrated experimental and Large-Eddy Simulation (LES) study is presented for homogeneous premixed combustion in a spark-ignition engine. The engine is a single-cylinder two-valve optical research engine with transparent liner and piston: the Transparent Combustion Chamber (TCC) engine. This is a relatively simple, open engine configuration that can be used for LES model development and validation by other research groups. Pressure-based combustion analysis, optical diagnostics and LES have been combined to generate new physical insight into the early stages of combustion. The emphasis has been on developing strategies for making quantitative comparisons between high-speed/high-resolution optical diagnostics and LES using common metrics for both the experiments and the simulations, and focusing on the important early flame development period. Results from two different LES turbulent combustion models are presented, using the same numerical methods and computational mesh. Both models yield Cycle-to-Cycle Variations (CCV) in combustion that are higher than what is observed in the experiments. The results reveal strengths and limitations of the experimental diagnostics and the LES models, and suggest directions for future diagnostic and simulation efforts. In particular, it has been observed that flame development between the times corresponding to the laminar-to-turbulent transition and 1% mass-burned fraction are especially important in establishing the subsequent combustion event for each cycle. This suggests a range of temporal and spatial scales over which future experimental and simulation efforts should focus

A Combined Patch-Clamp and Electrorotation Study of the Voltage- and Frequency-Dependent Membrane Capacitance Caused by Structurally Dissimilar Lipophilic Anions

Interactions of structurally dissimilar anionic compounds with the plasma membrane of HEK293 cells were analyzed by patch clamp and electrorotation. The combined approach provides complementary information on the lipophilicity, preferential affinity of the anions to the inner/outer membrane leaflet, adsorption depth and transmembrane mobility. The anionic species studied here included the well-known lipophilic anions dipicrylamine (DPA−), tetraphenylborate (TPB−) and [W2(CO)10(S2CH)]−, the putative lipophilic anion \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{B}}{\left( {{\text{CF}}_{3} } \right)}^{ - }_{4}$$\end{document} and three new heterocyclic W(CO)5 derivatives. All tested anions partitioned strongly into the cell membrane, as indicated by the capacitance increase in patch-clamped cells. The capacitance increment exhibited a bell-shaped dependence on membrane voltage. The midpoint potentials of the maximum capacitance increment were negative, indicating the exclusion of lipophilic anions from the outer membrane leaflet. The adsorption depth of the large organic anions DPA−, TPB− and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{B}}{\left( {{\text{CF}}_{3} } \right)}^{ - }_{4}$$\end{document} increased and that of W(CO)5 derivatives decreased with increasing concentration of mobile charges. In agreement with the patch-clamp data, electrorotation of cells treated with DPA− and W(CO)5 derivatives revealed a large dispersion of membrane capacitance in the kilohertz to megahertz range due to the translocation of mobile charges. In contrast, in the presence of TPB− and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{B}}{\left( {{\text{CF}}_{3} } \right)}^{ - }_{4}$$\end{document} no mobile charges could be detected by electrorotation, despite their strong membrane adsorption. Our data suggest that the presence of oxygen atoms in the outer molecular shell is an important factor for the fast translocation ability of lipophilic anions

What do aquaporin knockout studies tell us about fluid transport in epithelia?

The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however, debates over mechanism and pathway remain. Aquaporin (AQP) knockouts have been used by various research groups to test the hypothesis of an osmotic mechanism as well as to explore the paracellular versus transcellular pathway debate. Nonproportional reductions in the water permeability of a water-transporting epithelial cell (e.g., a reduction of around 80–90 %) compared to the reduction in overall water transport rate in the knockout animal (e.g., a reduction of 50–60 %) are commonly found. This nonproportionality has led to controversy over whether AQP knockout studies support or contradict the osmotic mechanism. Arguments raised for and against an interpretation supporting the osmotic mechanism typically have partially specified, implicit, or incorrect assumptions. We present a simple mathematical model of the osmotic mechanism with clear assumptions and, for models based on this mechanism, establish a baseline prediction of AQP knockout studies. We allow for deviations from isotonic/isosmotic conditions and utilize dimensional analysis to reduce the number of parameters that must be considered independently. This enables a single prediction curve to be used for multiple epithelial systems. We find that a simple, transcellular-only osmotic mechanism sufficiently predicts the results of knockout studies and find criticisms of this mechanism to be overstated. We note, however, that AQP knockout studies do not give sufficient information to definitively rule out an additional paracellular pathway

Field, capital and the policing habitus: nderstanding Bourdieu through The NYPD’s post-9/11 counterterrorism practices

This article extends existing Bourdieusian theory in criminology and security literature through examining the practices of the New York City Police Department in the post-9/11 counterterrorism field. This article makes several original contributions. First, it explores the resilient nature of the policing habitus, extending Bourdieusian criminological findings that habitus are entrenched and difficult to change. Second, this article examines the way the resilient habitus drives subordinate factions to displace dominant factions in a field’s established social hierarchy through boundary-pushing practices, a concept previously unexamined in Bourdieusian criminology. Drawing on original documentary analysis, this article uses the illustrative example of the NYPD’s post-9/11 counterterrorism practices, exploring how it sought to displace the existing social structure by using its aggressive policing habitus and an infusion of ‘War on Terror’ capital to challenge the dominant position of the FBI in the post-9/11 counterterrorism field. The NYPD’s habitus driven counterterrorism practices were novel and unprecedented, creating strain with both the FBI and local communities