Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.

Dynamical structure function identifiability conditions enabling signal structure reconstruction

Networks of controlled dynamical systems exhibit a variety of interconnection patterns that could be interpreted as the structure of the system. One such interpretation of system structure is a system's signal structure, characterized as the open-loop causal dependencies among manifest variables and represented by its dynamical structure function. Although this notion of structure is among the weakest available, previous work has shown that if no a priori structural information is known about the system, not even the Boolean structure of the dynamical structure function is identifiable. Consequently, one method previously suggested for obtaining the necessary a priori structural information is to leverage knowledge about target specificity of the controlled inputs. This work extends these results to demonstrate precisely the a priori structural information that is both necessary and sufficient to reconstruct the network from input-output data. This extension is important because it significantly broadens the applicability of the identifiability conditions, enabling the design of network reconstruction experiments that were previously impossible due to practical constraints on the types of actuation mechanisms available to the engineer or scientist. The work is motivated by the proteomics problem of reconstructing the Per-Arnt-Sim Kinase pathway used in the metabolism of sugars. © 2012 IEEE.

Closely correlating lower and upper bound plastic analysis of real slabs

An engineer assessing the load-carrying capacity of an existing reinforced concrete slab is likely to use elastic analysis to check the load at which the structure might be expected to fail in flexure or in shear. In practice, many reinforced concrete slabs are highly ductile in flexure, so an elastic analysis greatly underestimates the loads at which they fail in this mode. The use of conservative elastic analysis has led engineers to incorrectly condemn many slabs and therefore to specify unnecessary and wasteful flexural strengthening or replacement. The lower bound theorem is based on the same principles as the upper bound theorem used in yield line analysis, but any solution that rigorously satisfies the lower bound theorem is guaranteed to be a safe underestimate of the collapse load. Jackson presented a rigorous lower bound method that obtains very accurate results for complex real slabs.

Fabrication of high-aspect-ratio polymer microstructures and hierarchical textures using carbon nanotube composite master molds

Scalable and cost effective patterning of polymer structures and their surface textures is essential to engineer material properties such as liquid wetting and dry adhesion, and to design artificial biological interfaces. Further, fabrication of high-aspect-ratio microstructures often requires controlled deep-etching methods or high-intensity exposure. We demonstrate that carbon nanotube (CNT) composites can be used as master molds for fabrication of high-aspect-ratio polymer microstructures having anisotropic nanoscale textures. The master molds are made by growth of vertically aligned CNT patterns, capillary densification of the CNTs using organic solvents, and capillary-driven infiltration of the CNT structures with SU-8. The composite master structures are then replicated in SU-8 using standard PDMS transfer molding methods. By this process, we fabricated a library of replicas including vertical micro-pillars, honeycomb lattices with sub-micron wall thickness and aspect ratios exceeding 50:1, and microwells with sloped sidewalls. This process enables batch manufacturing of polymer features that capture complex nanoscale shapes and textures, while requiring only optical lithography and conventional thermal processing. © 2011 The Royal Society of Chemistry.

Polarity driven formation of InAs/GaAs hierarchical nanowire heterostructures

The structural and morphological characteristics of InAs/GaAs radial nanowire heterostructures were investigated using transmission electron microscopy. It has been found that the radial growth of InAs was preferentially initiated on the { 112 } A sidewalls of GaAs nanowires. This preferential deposition leads to extraordinarily asymmetric InAs/GaAs radial nanowire heterostructures. Such formation of radial nanowire heterostructures provides an opportunity to engineer hierarchical nanostructures, which further widens the potential applications of semiconductor nanostructures. © 2008 American Institute of Physics.

Enhanced integrated modelling approach to reconfiguring manufacturing enterprises

Dynamism and uncertainty are real challenges for present day manufacturing enterprises (MEs). Reasons include: an increasing demand for customisation, reduced time to market, shortened product life cycles and globalisation. MEs can reduce competitive pressure by becoming reconfigurable and change-capable. However, modern manufacturing philosophies, including agile and lean, must complement the application of reconfigurable manufacturing paradigms. Choosing and applying the best philosophies and techniques is very difficult as most MEs deploy complex and unique configurations of processes and resource systems, and seek economies of scope and scale in respect of changing and distinctive product flows. It follows that systematic methods of achieving model driven reconfiguration and interoperation of component based manufacturing systems are required to design, engineer and change future MEs. This thesis, titled Enhanced Integrated Modelling Approach to Reconfiguring Manufacturing Enterprises , introduces the development and prototyping a model-driven environment for the design, engineering, optimisation and control of the reconfiguration of MEs with an embedded capability to handle various types of change. The thesis describes a novel systematic approach, namely enhanced integrated modelling approach (EIMA), in which coherent sets of integrated models are created that facilitates the engineering of MEs especially their production planning and control (PPC) systems. The developed environment supports the engineering of common types of strategic, tactical and operational processes found in many MEs. The EIMA is centred on the ISO standardised CIMOSA process modelling approach. Early study led to the development of simulation models during which various CIMOSA shortcomings were observed, especially in its support for aspects of ME dynamism. A need was raised to structure and create semantically enriched models hence forming an enhanced integrated modelling environment. The thesis also presents three industrial case examples: (1) Ford Motor Company; (2) Bradgate Furniture Manufacturing Company; and (3) ACM Bearings Company. In order to understand the system prior to realisation of any PPC strategy, multiple process segments of any target organisation need to be modelled. Coherent multi-perspective case study models are presented that have facilitated process reengineering and associated resource system configuration. Such models have a capability to enable PPC decision making processes in support of the reconfiguration of MEs. During these case studies, capabilities of a number of software tools were exploited such as Arena®, Simul8®, Plant Simulation®, MS Visio®, and MS Excel®. Case study results demonstrated effectiveness of the concepts related to the EIMA. The research has resulted in new contributions to knowledge in terms of new understandings, concepts and methods in following ways: (1) a structured model driven integrated approach to the design, optimisation and control of future reconfiguration of MEs. The EIMA is an enriched and generic process modelling approach with capability to represent both static and dynamic aspects of an ME; and (2) example application cases showing benefits in terms of reduction in lead time, cost and resource load and in terms of improved responsiveness of processes and resource systems with a special focus on PPC; (3) identification and industrial application of a new key performance indicator (KPI) known as P3C the measuring and monitoring of which can aid in enhancing reconfigurability and responsiveness of MEs; and (4) an enriched modelling concept framework (E-MUNE) to capture requirements of static and dynamic aspects of MEs where the conceptual framework has the capability to be extended and modified according to the requirements. The thesis outlines key areas outlining a need for future research into integrated modelling approaches, interoperation and updating mechanisms of partial models in support of the reconfiguration of MEs.

Modeling the carbon nanofiber addressed liquid crystal microlens array from experimentally observed optical phenomena

This paper presents a novel method of using experimentally observed optical phenomena to reverse-engineer a model of the carbon nanofiber-addressed liquid crystal microlens array (C-MLA) using Zemax. It presents the first images of the optical profile for the C-MLA along the optic axis. The first working optical models of the C-MLA have been developed by matching the simulation results to the experimental results. This approach bypasses the need to know the exact carbon nanofiber-liquid crystal interaction and can be easily adapted to other systems where the nature of an optical device is unknown. Results show that the C-MLA behaves like a simple lensing system at 0.060-0.276 V/μm. In this lensing mode the C-MLA is successfully modeled as a reflective convex lens array intersecting with a flat reflective plane. The C-MLA at these field strengths exhibits characteristics of mostly spherical or low order aspheric arrays, with some aspects of high power aspherics. It also exhibits properties associated with varying lens apertures and strengths, which concur with previously theorized models based on E-field patterns. This work uniquely provides evidence demonstrating an apparent "rippling" of the liquid crystal texture at low field strengths, which were successfully reproduced using rippled Gaussian-like lens profiles. © 2014 Published by Elsevier B.V.

In vitro recording of neural activity using carbon nanosheet microelectrodes

The advent of nanotechnology has revolutionised our ability to engineer electrode interfaces. These are particularly attractive to measure biopotentials, and to study the nervous system. In this work, we demonstrate enhanced in vitro recording of neuronal activity using electrodes decorated with carbon nanosheets (CNSs). This material comprises of vertically aligned, free standing conductive sheets of only a few graphene layers with a high surfacearea- to-volume ratio, which makes them an interesting material for biomedical electrodes. Further, compared to carbon nanotubes, CNSs can be synthesised without the need for metallic catalysts like Ni, Co or Fe, thereby reducing potential cytotoxicity risks. Electrochemical measurements show a five times higher charge storage capacity, and an almost ten times higher double layer capacitance as compared to TiN. In vitro experiments were performed by culturing primary hippocampal neurons from mice on micropatterned electrodes. Neurophysiological recordings exhibited high signal-to-noise ratios of 6.4, which is a twofold improvement over standard TiN electrodes under the same conditions. © 2013 Elsevier Ltd. All rights reserved.

Briefing: Re-Engineering the City 2020-2050 - Urban Foresight and Transition Management

Cities may be responsible for up to 70% of global carbon emissions and 75% of global energy consumption and by 2050 it is estimated that 70% of the world's population could live in cities. The critical challenge for contemporary urbanism, therefore, is to understand how to develop the knowledge, capacity and capability for public agencies, the private sector and multiple users in city regions systemically to re-engineer their built environment and urban infrastructure in response to climate change and resource constraints. Re-Engineering the City 2020-2050: Urban Foresight and Transition Management (Retrofit 2050) is a major new interdisciplinary project funded under the Engineering and Physical Science Research Council's (EPSRC) Sustainable Urban Environments Programme which seeks to address this challenge. This briefing describes the background and conceptual framing of Retrofit 2050 project, its aims and objectives and research approach.

Self-organization, embodiment, and biologically inspired robotics.

Robotics researchers increasingly agree that ideas from biology and self-organization can strongly benefit the design of autonomous robots. Biological organisms have evolved to perform and survive in a world characterized by rapid changes, high uncertainty, indefinite richness, and limited availability of information. Industrial robots, in contrast, operate in highly controlled environments with no or very little uncertainty. Although many challenges remain, concepts from biologically inspired (bio-inspired) robotics will eventually enable researchers to engineer machines for the real world that possess at least some of the desirable properties of biological organisms, such as adaptivity, robustness, versatility, and agility.

Guidewire retention following central venous catheterisation: a human factors and safe design investigation.

BACKGROUND: Central Venous Catheterisation (CVC) has occasionally been associated with cases of retained guidewires in patients after surgery. In theory, this is a completely avoidable complication; however, as with any human procedure, operator error leading to guidewires being occasionally retained cannot be fully eliminated. OBJECTIVE: The work described here investigated the issue in an attempt to better understand it both from an operator and a systems perspective, and to ultimately recommend appropriate safe design solutions that reduce guidewire retention errors. METHODS: Nine distinct methods were used: observations of the procedure, a literature review, interviewing CVC end-users, task analysis construction, CVC procedural audits, two human reliability assessments, usability heuristics and a comprehensive solution survey with CVC end-users. RESULTS: The three solutions that operators rated most highly, in terms of both practicality and effectiveness, were: making trainees better aware of the potential guidewire complications and strongly emphasising guidewire removal in CVC training, actively checking that the guidewire is present in the waste tray for disposal, and standardising purchase of central line sets so that differences that may affect chances of guidewire loss is minimised. CONCLUSIONS: Further work to eliminate/engineer out the possibility of guidewires being retained is proposed.

Plasmons in vertically coupled InAs/GaAs quantum dots

We investigate plasmon excitations in a quantum wire that consists of an infinite one-dimensional array of vertically coupled InAs/GaAs strained quantum dots (QDs). The research is carried out in the framework of random-phase approximation using effective-mass theory. Our formalism is capable of studying plasmons with strong tunneling among QDs, which frustrate the conventionally adopted tight-binding approximation. Based on this formalism, a systematic study on the intraminiband or intrasubband plasmon in vertically coupled InAs/GaAs strained QDs is presented. It is found that an increase of the dot spacing will inevitably reduce the plasmon energy. In contrast, the role of dot height is relatively complex and depends on the dot spacing. The results demonstrate the possibility to engineer collective excitations in low dimensional systems by simply changing their geometric configuration.

Porous InP array-directed assembly of InAs nanostructure

Fascinating features of porous InP array-directed assembly of InAs nanostructures are presented. Strained InAs nanostructures are grown by molecular-beam epitaxy on electrochemical etched porous InP substrate. Identical porous substrate with different pore depths defines different growth modes. Shallow pores direct the formation of closely spaced InAs dots at the bottom. Deep pores lead to progressive covering of the internal surface of pores by epitaxial material followed by pore mouth shrinking. For any depth an obvious dot depletion feature occurs on top of the pore framework. This growth method presages a pathway to engineer quantum-dot molecules and other nanoelements for fancy physical phenomena. (c) 2006 American Institute of Physics.

Pockels effect in GaN/Al-x,Gal(1-x)N superlattice with different quantum structures - art. no. 69841G

The linear electro-optic (Pockels) effect of wurtzite gallium nitride (GaN) films and six-period GaN/AlxGa1-xN superlattices with different quantum structures were demonstrated by a polarization-maintaining fiber-optical Mach-Zehnder interferometer system with an incident light wavelength of 1.55 mu m. The samples were prepared on (0001) sapphire substrate by low-temperature metalorganic chemical vapor deposition (MOCVD). The measured coefficients of the GaN/AlxGa1-xN superlattices are much larger than those of bulk material. Taking advantage of the strong field localization due to resonances, GaN/AlxGa1-xN SL can be proposed to engineer the nonlinear responses.

A widely tunable continuous-time LPF for a direct conversion DBS tuner

A continuous-time 7th-order Butterworth Gm-C low pass filter (LPF) with on-chip automatic tuning circuit has been implemented for a direct conversion DBS tuner in 0.35μm SiGe BiCMOS technology. The filter's -3 dB cutoff frequency f0 can be tuned from 4 to 40 MHz. A novel on-chip automatic tuning scheme has been successfully realized to tune and lock the filter's cutoff frequency. Measurement results show that the filter has -0.5 dB passband gain, +/- 5% bandwidth accuracy, 30 nV/Hz~(1/2) input referred noise, -3 dBVrms passband IIP3, and 27 dBVrms stopband IIP3. The I/Q LPFs with the tuning circuit draw 13 mA (with f_0 = 20 MHz) from 5 V supply, and occupy 0.5 mm~2.