The potential role of walking and cycling to increase resilience of transport systems to future external shocks: creating an indicator of who could get to work by walking and cycling if there was no fuel for motorised transport

There are finite limits to resources, both extractable raw materials and planetary life support resources. Because of this, it is possible that there will be a severe and long lasting reduction in the fuel available for motorised transport which could manifest itself suddenly as a fuel shock. This thesis is concerned with the conceptual design, methodological development and application of a new spatially explicit transport policy indicator which estimates: Who could get to work tomorrow by walking and cycling if there was a fuel shock today? This thesis estimates the potential that walking and cycling have to increase resilience to fuel shocks in the period immediately after the fuel shock. A conceptual model of resilience to fuel shocks by individuals was devised. A novel hybrid static spatial microsimulation technique was developed. It was used to generate a population of individuals with the appropriate attributes to estimate for large populations the capacity to make journeys using only walking and cycling. This modelling process is generic and can be used to generate indicator results wherever suitable data exist. Using a simple scenario of a fuel shock which occurs today, current data could be used to estimate the indicator. A case study using the census data covering England, the Health Survey For England and other data sets was produced. Validation of the modelling process informs the analysis of the results. The results demonstrate the ability of the indicator to show variation between areas, in both a base case and when specific policy measures are applied. The base case indicator estimated that nationally in England only 44% (±4.85%) of individuals have capacity to commute to work by walking and cycling following a fuel shock. A local analysis of Leeds identified the spatial patterns of attributes which influence the indicator, allowing greater understanding of the geographical influences on capacity to travel by active modes. A policy package increasing bicycle availability, health and fitness and ensuring the ability of children to travel to school without needing adult escort was found to have a significant effect in 99% of English Output Areas. The indicator calculation methodology has produced significant improvements in the estimation of capacity to travel by active modes. Assuming everyone can cycle 8km (a common assumption in transport planning) overestimates capacity of the population to commute by active modes. The indicator identified a mean difference of 26% across all OAs. By considering constraints the indicator estimates of mean maximum distance travel distance by active modes differ by 73% compared to methods which ignore constraints. The indicator produced is policy relevant; The indicator can be judged as a good indicator when assessed against criteria for good indicators established by other workers. The modelling process is generic and can be applied to other scenarios. The results were presented at different extents and resolutions; making a useful and flexible spatially explicit indicator tool

Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division

Rac1 regulates a wide variety of cellular processes. The polybasic region of the Rac1 C terminus functions both as a plasma membrane–targeting motif and a nuclear localization sequence (NLS). We show that a triproline N-terminal to the polybasic region contributes to the NLS, which is cryptic in the sense that it is strongly inhibited by geranylgeranylation of the adjacent cysteine. Subcellular fractionation demonstrated endogenous Rac1 in the nucleus and Triton X-114 partition revealed that this pool is prenylated. Cell cycle–blocking agents, synchronization of cells stably expressing low levels of GFP-Rac1, and time-lapse microscopy of asynchronous cells revealed Rac1 accumulation in the nucleus in late G2 and exclusion in early G1. Although constitutively active Rac1 restricted to the cytoplasm inhibited cell division, activated Rac1 expressed constitutively in the nucleus increased the mitotic rate. These results show that Rac1 cycles in and out of the nucleus during the cell cycle and thereby plays a role in promoting cell division

Repurposable hardware in smart photonic components

Key to the development of cost effective integrated components is low cost, low power circuitry capable of being repurposed from providing manufacturing based functions, such as characterisation and calibration, to operational control functions. Although these individual functions are well known, efficient and low cost implementations are required to enable competitive module pricing. In the case of an optical Mach Zehnder Modulator (MZM), bias currents require complex control functions, for example based around digitally synthesized sinusoidal pilot tones and harmonic detection via filters [1][2]. Control methods making use of calibrated laboratory equipment have been proposed [2], whereas here we consider the practical adoption of these methods with low cost and low power components which could be readily integrated into an optical module. In particular we investigate the behaviour and capabilities required for automatic digital bias control functionality implemented in a small gate count, low cost Field Programmable Gate Array (FPGA) when used in conjunction with a MZM. We assess the suitability of highly efficient implementations of DSP functions within the bias controller, such as digital filters, for example investigating the use of a computationally efficient algorithm for computing a single component of a discrete Fourier transform [3], and demonstrate the viability of using low cost digital hardware to implement a circuit capable of monitoring the MZM transfer function. The concept of creating cost effective, repurposable hardware is crucial for implementation and inclusion in optical devices deployed in communications networks and beyond

Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion

Rap1 and Ras are closely related GTPases that share some effectors but have distinct functions. We studied the subcellular localization of Rap1 and its sites of activation in living cells. Both GFP-tagged Rap1 and endogenous Rap1 were localized to the plasma membrane (PM) and endosomes. The PM association of GFP-Rap1 was dependent on GTP binding, and GFP-Rap1 was rapidly up-regulated on this compartment in response to mitogens, a process blocked by inhibitors of endosome recycling. A novel fluorescent probe for GTP-bound Rap1 revealed that this GTPase was transiently activated only on the PM of both fibroblasts and T cells. Activation on the PM was blocked by inhibitors of endosome recycling. Moreover, inhibition of endosome recycling blocked the ability of Rap1 to promote integrin-mediated adhesion of T cells. Thus, unlike Ras, the membrane localizations of Rap1 are dynamically regulated, and the PM is the principle platform from which Rap1 signaling emanates. These observations may explain some of the biological differences between these GTPases

Unrepeatered DP-QPSK transmission over 352.8 km SMF using random DFB fiber laser amplification

Unrepeatered 100 Gbit/s per channel wave-divisionmultiplexed dual-polarization-QPSK transmission with random distributed feedback fiber laser-based Raman amplification using fiber Bragg grating is demonstrated. Transmission of 1.4 Tb/s (14 × 100 Gbit/s) was possible in 352.8 km link and 2.2 Tb/s (22 × 100 Gbit/s) was achieved in 327.6 km without employing remote optically pumped amplifier or speciality fibers

Performance characterization of high gain, high output power and low noise cascaded broadband discrete Raman amplifiers

In this paper, gain, noise and nonlinear performance characterization of cascaded broadband discrete Raman amplifiers with different gain fibre combinations is presented. We numerically demonstrate the design of a backward-pumped cascaded dual stage broadband (∼70 nm) discrete Raman amplifier with high gain (∼19 dB), low noise (∼ 6 dB noise figure) and lower nonlinear penalty by optimizing two different types of gain fibres

NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane

Isoprenylcysteine carboxyl methyltransferase (ICMT) is the third of three enzymes that sequentially modify the C-terminus of CaaX proteins, including RAS. Although all four RAS proteins are substrates for ICMT, each traffics to membranes differently by virtue of their hypervariable regions that are differentially palmitoylated. We found that among RAS proteins, NRAS was unique in requiring ICMT for delivery to the PM, a consequence of having only a single palmitoylation site as its secondary affinity module. Although not absolutely required for palmitoylation, acylation was diminished in the absence of ICMT. Photoactivation and FRAP of GFP-NRAS revealed increase flux at the Golgi, independent of palmitoylation, in the absence of ICMT. Association of NRAS with the prenyl-protein chaperone PDE6δ also required ICMT and promoted anterograde trafficking from the Golgi. We conclude that carboxyl methylation of NRAS is required for efficient palmitoylation, PDE6δ binding, and homeostatic flux through the Golgi, processes that direct delivery to the plasma membrane.</p

PKC Regulates a Farnesyl-Electrostatic Switch on K-Ras that Promotes its Association with Bcl-Xl on Mitochondria and Induces Apoptosis

K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-Xl. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-Xl. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S18

Metropolitan Contractor Improvement Partnership 2013-2018 Strategic Plan

25 pagesThis report, the Metropolitan Contractor Improvement Partnership 2013-2018 Strategic Plan, identifies the key issues facing the organization, and suggests goals, strategies, and actions to address those issues.Economic Development Administration University Cente

Pollen sterols are associated with phylogenetics and environment but not with pollinators

Phytosterols are primary plant metabolites that have fundamental structural and regulatory functions. They are also essential nutrients for phytophagous insects, including pollinators, that cannot synthesize sterols. Despite the well-described composition and diversity in vegetative plant tissues, few studies have examined phytosterol diversity in pollen. We quantified 25 pollen phytosterols in 122 plant species (105 genera, 51 families) to determine their composition and diversity across plant taxa. We searched literature and databases for plant phylogeny, environmental conditions, and pollinator guilds of the species to examine the relationships with pollen sterols. 24-methylenecholesterol, sitosterol and isofucosterol were the most common and abundant pollen sterols. We found phylogenetic clustering of twelve individual sterols, total sterol content and sterol diversity, and of sterol groupings that reflect their underlying biosynthesis pathway (24 carbon alkylation, ring B desaturation). Plants originating in tropical-like climates (higher mean annual temperature, lower temperature seasonality, higher precipitation in wettest quarter) were more likely to record higher pollen sterol content. However, pollen sterol composition and content showed no clear relationship with pollinator guilds. Our study is the first to show that pollen sterol diversity is phylogenetically clustered and that pollen sterol content may adapt to environmental conditions