Effect of a zero g environment on flammability limits as determined using a standard flammability tube apparatus

Flammability limits in a zero gravity environment were defined. Key aspects of a possible spacelab experiment were investigated analytically, experimentally on the bench, and in drop tower facilities. A conceptual design for a spacelab experiment was developed

Estimation of the vortex length scale and intensity from two-dimensional samples

A method is proposed for estimating flow features that influence flame wrinkling in reciprocating internal combustion engines, where traditional statistical measures of turbulence are suspect. Candidate methods were tested in a computed channel flow where traditional turbulence measures are valid and performance can be rationally evaluated. Two concepts are tested. First, spatial filtering is applied to the two-dimensional velocity distribution and found to reveal structures corresponding to the vorticity field. Decreasing the spatial-frequency cutoff of the filter locally changes the character and size of the flow structures that are revealed by the filter. Second, vortex length scale and intensity is estimated by computing the ensemble-average velocity distribution conditionally sampled on the vorticity peaks. The resulting conditionally sampled 'average vortex' has a peak velocity less than half the rms velocity and a size approximately equal to the two-point-correlation integral-length scale

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

Optimizing the Stark-decelerator beamline for the trapping of cold molecules using evolutionary strategies

We demonstrate feedback control optimization for the Stark deceleration and trapping of neutral polar molecules using evolutionary strategies. In a Stark-decelerator beamline pulsed electric fields are used to decelerate OH radicals and subsequently store them in an electrostatic trap. The efficiency of the deceleration and trapping process is determined by the exact timings of the applied electric field pulses. Automated optimization of these timings yields an increase of 40 % of the number of trapped OH radicals.Comment: 7 pages, 4 figures (RevTeX) (v2) minor corrections (v3) no changes to manuscript, but fix author list in arXiv abstrac

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

Pressure Dependence of the Elastic Moduli in Aluminum Rich Al-Li Compounds

I have carried out numerical first principles calculations of the pressure dependence of the elastic moduli for several ordered structures in the Aluminum-Lithium system, specifically FCC Al, FCC and BCC Li, L1_2 Al_3Li, and an ordered FCC Al_7Li supercell. The calculations were performed using the full potential linear augmented plane wave method (LAPW) to calculate the total energy as a function of strain, after which the data was fit to a polynomial function of the strain to determine the modulus. A procedure for estimating the errors in this process is also given. The predicted equilibrium lattice parameters are slightly smaller than found experimentally, consistent with other LDA calculations. The computed elastic moduli are within approximately 10% of the experimentally measured moduli, provided the calculations are carried out at the experimental lattice constant. The LDA equilibrium shear modulus C11-C12 increases from 59.3 GPa in Al, to 76.0 GPa in Al_7Li, to 106.2 GPa in Al_3Li. The modulus C_44 increases from 38.4 GPa in Al to 46.1 GPa in Al_7Li, then falls to 40.7 GPa in Al_3Li. All of the calculated elastic moduli increase with pressure with the exception of BCC Li, which becomes elastically unstable at about 2 GPa, where C_11-C_12 vanishes.Comment: 17 pages (REVTEX) + 7 postscript figure

Multiscale modelling of vascular tumour growth in 3D: the roles of domain size & boundary condition

We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour

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

Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins

Interferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver, and gastrointestinal tract. Humans have four IFNλs (1–4), where IFNλ1–3 show ~80%–95% homology, and IFNλ4 is the most divergent displaying only ~30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFNλ4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study, we address whether differences in antiviral signalling exist between IFNλ4 variants in human hepatocyte and intestinal cells, comparing them to IFNλ3. We demonstrate that compared to IFNλ3, wild-type human IFNλ4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally occurring variants P70S and K154E in both cell types. IFNλ4’s distinct antiviral response was more rapid yet transient compared to IFNλ1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFNλs and cell lines. Furthermore, an IFNλ4-like receptor-interacting interface failed to alter IFNλ1’s kinetics. Together, our data provide further evidence that major functional differences exist within the IFNλ gene family. These results highlight the possible tissue specialisation of IFNλs and encourage further investigation of the divergent, non-redundant activities of IFNλ4 and other IFNλs

A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR

Background: Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern. Methods: Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas. Results EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations. Conclusions: Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas