Haemodynamics Regulate Fibronectin Assembly via PECAM

Fibronectin (FN) assembly and fibrillogenesis are critically important in both development and the adult organism, but their importance in vascular functions is not fully understood. Here we identify a novel pathway by which haemodynamic forces regulate FN assembly and fibrillogenesis during vascular remodelling. Induction of disturbed shear stress in vivo and in vitro resulted in complex FN fibril assembly that was dependent on the mechanosensor PECAM. Loss of PECAM also inhibited the cell-intrinsic ability to remodel FN. Gain- and loss-of-function experiments revealed that PECAM-dependent RhoA activation is required for FN assembly. Furthermore, PECAM−/− mice exhibited reduced levels of active β1 integrin that were responsible for reduced RhoA activation and downstream FN assembly. These data identify a new pathway by which endothelial mechanotransduction regulates FN assembly and flow-mediated vascular remodelling

tRNAs as Antibiotic Targets

Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed

Compressible boundary layers with sharp pressure gradients

The work of this thesis was undertaken as a C.A.S.E. award project in collaboration with Rolls-Royce to examine compressible laminar boundary layers with sharp adverse pressure-gradients. Much of the work is devoted to the solution of two important particular problems. The first flow considered is that along a semi-infinite flat plate with uniform pressure when X X₀ being so chosen that the boundary layer is just on the point of separation for all X > X₀. Immediately downstream of X₀ there is a sharp pressure rise to which the flow reacts mainly in a thin inner sublayer; so inner and outer asymptotic expansions are derived and matched for the stream function and a function of the temperature. Throughout the thesis the ratio of the viscosity to the absolute temperature is taken to be a function of x, the distance along the wall, alone, and the Illingworth-Stewartson transformation is applied. The Prandtl number, σ, is taken to be of order unity and detailed results are presented for σ= 1 and 0.72. The second flow considered is that along a finite flat plate where the transformed external velocity U₁(X) is chosen such that U₁(X) = u₀(-X/L)[super]ε, where O< ε <<1, is the transformed length of the plate and X represents transformed distance downstream from the trailing edge. The skin friction, position of separation and heat transfer right up to separation are determined. On the basis of these two solutions, another solution which is not presented in detail, and a solution (due to Curie) to a fourth sharp pressure gradient problem, a general Stratford-type method for computing compressible boundary layers is derived, which may be used to predict the position of separation, skin friction, heat transfer, displacement and momentum thicknesses for a compressible boundary layer with an unfavourable pressure gradient. In all this work techniques of series analysis are used to good effect. This led us to look at another boundary-layer problem in which such techniques could be used, one in which two parallel infinite disks are initially rotating with angular velocity Ω about a common axis in incompressible fluid, the appropriate Reynolds number being very large. Suddenly the angular velocity of one of the disks is reversed. A new examination of this problem is presented in the appendix to the thesis

Ethical Conundrums and Virtual Humans

This paper explores ethical conundrums and virtual humans through building upon a post-Kantian framework, and one emerging from what is known as New Materialism. It begins by presenting the recent research and literature on virtual humans and suggesting that the central ethical conundrums that need to be examined are those of agency and values. The paper then argues that a combination of Luciano Floridi’s approach and one developed from New Materialism, namely modest ethics, offers a means of engaging with the ethical conundrums of virtual humans. It is argued that as yet there is little evidence for a democratic design process for virtual humans nor is there evidence about the possible impact virtual humans may have on a postdigital society. The paper concludes by suggesting that there need to be more open processes for debate which bring to light the values that are being built into these profound developments by the experts and focuses on using a modest ethics approach

Toroidal Variable-Line-Space Gratings: The Good, the Bad and The Ugly

Toroidal variable-line-space (VLS) gratings are an important factor in the design of an efficient VUV solar telescope that will measure the CIV (155nm) and MgII (280nm) emissions lines in the Sun's transition region. In 1983 Kita and Harada described spherical VLS gratings but the technology to commercially fabricate these devices is a recent development, especially for toroidal surfaces. This paper will describe why this technology is important in the development of the Solar Ultraviolet Magnetograph Investigation (SUMI) sounding rocket program (the good), the delays due to the conversion between the TVLS grating design and the optical fabrication (the bad), and finally the optical testing, alignment and tolerancing of the gratings (the ugly). The Solar Ultraviolet Magnetograph Investigation, SUMI, has been reported in several papers since this program began in 2000. The emphasis of this paper is to describe SUMI's Toroidal Variable-Line-Space (TVLS) gratings. These gratings help SUMI meet its scientific goals which require both high spectral resolution and high optical efficiency for magnetic field measurements in the vacuum ultraviolet wavelength band of the solar spectrum (the good). Unfortunately, the technology readiness level of these gratings has made their implementation difficult, especially for a sounding rocket payload (the bad). Therefore, this paper emphasizes the problems and solutions that were developed to use these gratings in SUMI (the ugly). Section 2 contains a short review of the scientific goals of SUMI and why this mission is important in the understanding of the 3D structure of the magnetic field on the Sun. The flight hardware that makes up the SUMI payload is described in Section 3 with emphasis on those components that affect the TVLS gratings. Section 4 emphasizes the alignment, testing and optical modeling that were developed to optimize the performance of these gratings

Dynamical control of the mesosphere by orographic and non-orographic gravity wave drag during the extended northern winters of 2006 and 2009

A version of the Canadian Middle Atmosphere Model (CMAM) that is nudged toward reanalysis data up to 1 hPa is used to examine the impacts of parameterized orographic and non-orographic gravity wave drag (OGWD and NGWD) on the zonal-mean circulation of the mesosphere during the extended northern winters of 2006 and 2009 when there were two large stratospheric sudden warmings. The simulations are compared to Aura Microwave Limb Sounder (MLS) observations of mesospheric temperature, carbon monoxide (CO) and derived zonal winds. The control simulation, which uses both OGWD and NGWD, is shown to be in good agreement with MLS. The impacts of OGWD and NGWD are assessed using simulations in which those sources of wave drag are removed. In the absence of OGWD the mesospheric zonal winds in the months preceding the warmings are too strong, causing increased mesospheric NGWD, which drives excessive downwelling, resulting in overly large lower mesospheric values of CO prior to the warming. NGWD is found to be most important following the warmings when the underlying westerlies are too weak to allow much vertical propagation of the orographic gravity waves to the mesosphere. NGWD is primarily responsible for driving the circulation that results in the descent of CO from the thermosphere following the warmings. Zonal mean mesospheric winds and temperatures in all simulations are shown to be strongly constrained by (i.e. slaved to) the stratosphere. Finally, it is demonstrated that the responses to OGWD and NGWD are non-additive due to their dependence and influence on the background winds and temperatures

Structural characterization of antibiotic self-immunity tRNA synthetase in plant tumour biocontrol agent

Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin. Using a combination of structural, biochemical and biophysical approaches, we show that AgnB2 evolved structural changes so as to resist the antibiotic by eliminating the tRNA-dependence of TM84 binding. Mutagenesis of key resistance determinants results in mutants adopting an antibiotic-sensitive phenotype. This study illuminates the evolution of resistance in self-immunity genes and provides mechanistic insights into a fascinating tRNA-dependent antibiotic with applications for the development of anti-infectives and the prevention of biocontrol emasculation

Separating the dynamical effects of climate change and ozone depletion. Part I: Southern Hemisphere stratosphere

A version of the Canadian Middle Atmosphere Model that is coupled to an ocean is used to investigate the separate effects of climate change and ozone depletion on the dynamics of the Southern Hemisphere (SH) stratosphere. This is achieved by performing three sets of simulations extending from 1960 to 2099: 1) greenhouse gases (GHGs) fixed at 1960 levels and ozone depleting substances (ODSs) varying in time, 2) ODSs fixed at 1960 levels and GHGs varying in time, and 3) both GHGs and ODSs varying in time. The response of various dynamical quantities to theGHGand ODS forcings is shown to be additive; that is, trends computed from the sum of the first two simulations are equal to trends from the third. Additivity is shown to hold for the zonal mean zonal wind and temperature, the mass flux into and out of the stratosphere, and the latitudinally averaged wave drag in SH spring and summer, as well as for final warming dates. Ozone depletion and recovery causes seasonal changes in lower-stratosphere mass flux, with reduced polar downwelling in the past followed by increased downwelling in the future in SH spring, and the reverse in SH summer. These seasonal changes are attributed to changes in wave drag caused by ozone-induced changes in the zonal mean zonal winds. Climate change, on the other hand, causes a steady decrease in wave drag during SH spring, which delays the breakdown of the vortex, resulting in increased wave drag in summe

Student Ensemble: Wind Symphony

Center for the Performing ArtsNovember 17, 2011Thursday Evening8:00 p.m