Evaluating Many Treatments and Biomarkers in Oncology: A New Design

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.

New design of a multi-jet target for quasi phase matching

An improved dual-gas quasi-phase matching (QPM) foil target for high harmonic generation (HHG) is presented. The target can be setup with 12 individual gas inlets each feeding multiple nozzles separated by a minimum distance of 10 μm. Three-dimensional gas density profiles of these jets were measured using a Mach-Zehnder Interferometer. These measurements reveal how the jets influence the density of gas in adjacent jets and how this leads to increased local gas densities. The analysis shows that the gas profiles of the jets are well defined up to a distance of about 300 μm from the orifice. This target design offers experimental flexibility, not only for HHG/QPM investigations, but also for a wide range of experiments due to the large number of possible jet configurations. We demonstrate the application to controlled phase tuning in the extreme ultraviolet using a 1 kHz-10 mJ-30 fs-laser system where interference between two jets in the spectral range from 17 to 30 nm was observed.

Creating New Design-Build-Test Experiences as Outputs of Undergraduate Design-Build-Test Projects

This paper describes a methodology of using individual engineering undergraduate student projects as a means of effectively and efficiently developing new Design-Build-Test (DBT) learning experiences and challenges.
A key aspect of the rationale for this approach is that it benefits all parties. The student undertaking the individual project gets an authentic experience of producing a functional artefact, which has been the result of a design process that addresses conception, design, implementation and operation. The supervising faculty member benefits from live prototyping of new curriculum content and resources with a student who is at a similar level of knowledge and experience as the intended end users of the DBT outputs. The multiple students who ultimately undertake the DBT experiences / challenges benefit from the enhanced nature of a learning experience which has been “road tested” and optimised.
To demonstrate the methodology the paper will describe a case study example of an individual project completed in 2015. This resulted in a DBT design challenge with a theme of designing a catapult for throwing table tennis balls, the device being made from components laser cut from medium density fibreboard (MDF). Further three different modes of operation will be described which use the same resource materials but operate over different timescales and with different learning outcomes, from an icebreaker exercise focused on developing team dynamics through to full DBT where students get an opportunity to experience the full impact of their design decisions by competing against other students with a catapult they have designed and built themselves.

Design and optimization of FinFETs for ultra-low-voltage analog applications

In this paper, we analyze the enormous potential of engineering source/drain extension (SDE) regions in FinFETs for ultra-low-voltage (ULV) analog applications. SDE region design can simultaneously improve two key analog figures of merit (FOM)-intrinsic de gain (A(vo)) and cutoff frequency (f(T)) for 60 and 30 nm FinFETs operated at low drive current (J(ds) = 5 mu A/mu m). The improved Avo and fT are nearly twice compared to those of devices with abrupt SDE regions. The influence of the SDE region profile and its impact on analog FOM is extensively analyzed. Results show that SDE region optimization provides an additional degree of freedom apart from device parameters (fin width and aspect ratio) to design future nanoscale analog devices. The results are analyzed in terms of spacer-to-straggle ratio a new design parameter for SDE engineered devices. This paper provides new opportunities for realizing future ULV/low-power analog design with FinFETs.

Use of room temperature ionic liquids in gas sensor design

The attainable steady-state limiting currents and time responses of membrane-covered and membrane-independent gas sensors incorporating different electrode and electrolyte materials have been compared. A new design comprising a membrane-free microelectrode modified with a thin layer of a room temperature ionic liquid is considered. While the use of ionic liquid as electrolyte eliminates the need for a membrane and added supporting electrolyte, the slower diffusion of analyte within the more viscous medium results in slower time responses. Such sensors do, however, have potential application in more extreme operating conditions, such as high temperature and pressure, where traditional solvents would volatise.

Design of a salisbury screen absorber using frequency selective surfaces to improve bandwidth and angular stability performance

A new design method that greatly enhances the reflectivity bandwidth and angular stability beyond what is possible with a simple Salisbury screen is described. The performance improvement is obtained from a frequency selective surface (FSS) which is sandwiched between the outermost 377 Ω/square resistive sheet and the ground plane. This is designed to generate additional reflection nulls at two predetermined frequencies by selecting the size of the two unequal length printed dipoles in each unit cell. A multiband Salisbury screen is realised by adjusting the reflection phase of the FSS to position one null above and the other below the inherent absorption band of the structure. Alternatively by incorporating resistive elements midway on the dipoles, it is shown that the three absorption bands can be merged to create a structure with a −10 dB reflectivity bandwidth which is 52% larger and relatively insensitive to incident angle compared to a classical Salisbury screen having the same thickness. CST Microwave Studio was used to optimise the reflectivity performance and simulate the radar backscatter from the structure. The numerical results are shown to be in close agreement with bistatic measurements for incident angles up to 40° over the frequency range 5.4−18 GHz.

An Autopilot Based on a Local Control Network Design for an Unmanned Surface Vehicle

Over recent years, a number of marine autopilots designed using linear techniques have underperformed owing to their inability to cope with nonlinear vessel dynamics. To this end, a new design framework for the development of nonlinear autopilots is proposed herein. Local control networks (LCNs) can be used in the design of nonlinear control systems. In this paper, a LCN approach is taken in the design of a nonlinear autopilot for controlling the nonlinear yaw dynamics of an unmanned surface vehicle known as Springer. It is considered the approach is the first of its kind to be used in marine control systems design. Simulation results are presented and the performance of the nonlinear autopilot is compared with that of an existing Springer linear quadratic Gaussian (LQG) autopilot using standard system performance criteria. From the results it can be concluded the LCN autopilot out performed that based on LQG techniques in terms of the selected criteria. Also it provided more energy saving control strategies and would thereby increase operational duration times for the vehicle during real-time missions.

Shortening design time through multiplatform simulations with a portable OpenCL golden-model: the LDPC decoder case

Hardware designers and engineers typically need to explore a multi-parametric design space in order to find the best configuration for their designs using simulations that can take weeks to months to complete. For example, designers of special purpose chips need to explore parameters such as the optimal bitwidth and data representation. This is the case for the development of complex algorithms such as Low-Density Parity-Check (LDPC) decoders used in modern communication systems. Currently, high-performance computing offers a wide set of acceleration options, that range from multicore CPUs to graphics processing units (GPUs) and FPGAs. Depending on the simulation requirements, the ideal architecture to use can vary. In this paper we propose a new design flow based on OpenCL, a unified multiplatform programming model, which accelerates LDPC decoding simulations, thereby significantly reducing architectural exploration and design time. OpenCL-based parallel kernels are used without modifications or code tuning on multicore CPUs, GPUs and FPGAs. We use SOpenCL (Silicon to OpenCL), a tool that automatically converts OpenCL kernels to RTL for mapping the simulations into FPGAs. To the best of our knowledge, this is the first time that a single, unmodified OpenCL code is used to target those three different platforms. We show that, depending on the design parameters to be explored in the simulation, on the dimension and phase of the design, the GPU or the FPGA may suit different purposes more conveniently, providing different acceleration factors. For example, although simulations can typically execute more than 3x faster on FPGAs than on GPUs, the overhead of circuit synthesis often outweighs the benefits of FPGA-accelerated execution.

GiveMe Shelter: a people-centred design process for promoting independent inquiry-led learning in engineering

It has become increasingly common for tasks traditionally carried out by engineers to be undertaken by technicians and technologist with access to sophisticated computers and software that can often perform complex calculations that were previously the responsibility of engineers. Not surprisingly, this development raises serious questions about the future role of engineers and the education needed to address these changes in technology as well as emerging priorities from societal to environmental challenges. In response to these challenges, a new design module was created for undergraduate engineering students to design and build temporary shelters for a wide variety of end users from refugees, to the homeless and children. Even though the module provided guidance on principles of design thinking and methods for observing users needs through field studies, the students found it difficult to respond to needs of specific end users but instead focused more on purely technical issues.

EMI Suppression in an Aircraft Cooling Vent

Digital avionics systems are increasingly under threat from external electromagnetic interference (EMI). The same avionics systems require a thermal cooling mechanism and one method of providing this is to mount an air vent on the body of the aircraft. For the first time, a nacelle-mounted air vent that may expose the flight critical full authority digital engine controller (FADEC) to high intensity radiated fields (HIRF) is examined. The reflection/transmission characteristics of the vent are reported and the current shielding method employed is shown to provide a low shielding level (5 dB at 18 GHz). A new design has been proposed, providing over 100 dB of attenuation at 18 GHz. To the authors' knowledge this is the first time this shielding method has been applied to aircraft air vents.

Multiplier-less realization of a poly-phase filter using LUT-based FPGAs

In DSP applications such as fixed transforms and filtering, the full flexibility of a general-purpose multiplier is not required and only a limited range of values is needed on one of the multiplier inputs. A new design technique has been developed for deriving multipliers that operate on a limited range of multiplicands. This can be used to produce FPGA implementations of DSP systems where area is dramatically improved. The paper describes the technique and its application to the design of a poly-phase filter on a Virtex FPGA. A 62% area reduction and 7% speed increase is gained when compared to an equivalent design using general purpose multipliers. It is also compared favourably to other known fixed coefficient approaches.

Dramaturgy as a Model for Geographically Displaced Collaborations: Views from Within and Views from Without

The network is currently not only widely used for performative actions, but also extensively theorised. However, the artistic strategies in networked environments and the ways in which these new performance practices and cultural contexts can give rise to new design approaches have not been equally explored. This article therefore investigates the notion of dramaturgy as it provides a useful framework for addressing design strategies and performative relationships in networked environments. It is argued that dramaturgies suggest a robust method for understanding artistic practices in the network. The author refers to two different viewpoints that emerge in networked practice, which are entitled ;views from within' and ;views from without'. The article gives a brief overview of the history and the theories of the network. It then looks at the histories of dramaturgies in order to better understand artistic strategies, and in order to enhance collaborative work in network performance environments.

How crucial is back gate misalignment/oversize in double gate MOSFETs for ultra-low-voltage analog/rf applications?

In the present work, by investigating the influence of source/drain (S/D) extension region engineering (also known as gate-underlap architecture) in planar Double Gate (DG) SOI MOSFETs, we offer new design insights to achieve high tolerance to gate misalignment/oversize in nanoscale devices for ultra-low-voltage (ULV) analog/rf applications. Our results show that (i) misaligned gate-underlap devices perform significantly better than DC devices with abrupt source/drain junctions with identical misalignment, (ii) misaligned gate underlap performance (with S/D optimization) exceeds perfectly aligned DG devices with abrupt S/D regions and (iii) 25% back gate misalignment can be tolerated without any significant degradation in cut-off frequency (f(T)) and intrinsic voltage gain (A(VO)). Gate-underlap DG devices designed with spacer-to-straggle ratio lying within the range 2.5 to 3.0 show best tolerance to misaligned/oversize back gate and indeed are better than self-aligned DG MOSFETs with non-underlap (abrupt) S/D regions. Impact of gate length and silicon film thickness scaling is also discussed. These results are very significant as the tolerable limit of misaligned/oversized back gate is considerably extended and the stringent process control requirements to achieve self-alignment can be relaxed for nanoscale planar ULV DG MOSFETs operating in weak-inversion region. The present work provides new opportunities for realizing future ULV analog/rf design with nanoscale gate-underlap DG MOSFETs. (C) 2008 Elsevier Ltd. All rights reserved.

Climate Adaptation: The future of extra-care housing for the elderly in the United Kingdom.

This paper describes the result of a project to develop climate adaptation design strategies funded by the UK’s Technology Strategy Board. The aim of the project was to look at the effects of climate change in the distant future (2080) on a vulnerable group such as older people with special needs and see how architectural design strategies and technologies may be used today to help mitigate problems ahead caused by climate change.
Older people are the most vulnerable sector of society and are particularly at risk in extreme weather, either excess cold in winter or continual high temperatures in summer. In the UK it is predicted that average temperatures may rise by as much as 8 degrees in Summer by 2080 and there will be a 20% greater chance of extreme weather events. This will place extreme stress on the building stock which is designed for today’s mild maritime climate.
The project took a current proposal for an extra-care home for the elderly designed to 2010 regulations and developed a road map to 2080 using climate models developed by the UK Meteorological Office. This allowed the current design to be assessed using future climatic data, proposals for improvement of the scheme to be made within existing constraints and also a new scheme to be developed from first principals using this data, and projections of new technologies that will be available. By comparing these schemes, the approach allowed a reassessment of the initial scheme, and allowed a new design to be developed that offered a more flexible solution incorporating future retrofit which allows new renewable technologies for heating, cooling and water storage to be added at a later date.

Numerically Investigating the Effects of Cross-Links in Scaled Microchannel Heat Sinks

Thermal management as a method of heightening performance in miniaturized electronic devices using microchannel heat sinks has recently become of interest to researchers and the industry. One of the current challenges is to design heat sinks with uniform flow distribution. A number of experimental studies have been conducted to seek appropriate designs for microchannel heat sinks. However, pursuing this goal experimentally can be an expensive endeavor. The present work investigates the effect of cross-links on adiabatic two-phase flow in an array of parallel channels. It is carried out using the three dimensional mixture model from the computational fluid dynamics software, FLUENT 6.3. A straight channel and two cross-linked channel models were simulated. The cross-links were located at 1/3 and 2/3 of the channel length, and their widths were one and two times larger than the channel width. All test models had 45 parallel rectangular channels, with a hydraulic diameter of 1.59 mm. The results showed that the trend of flow distribution agrees with experimental results. A new design, with cross-links incorporated, was proposed and the results showed a significant improvement of up to 55% on flow distribution compared with the standard straight channel configuration without a penalty in the pressure drop. Further discussion about the effect of cross-links on flow distribution, flow structure, and pressure drop was also documented.