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Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducing de novo sterol biosynthesis and preventing lipid-mediated induction of ATF4. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether, our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.

Spatially offset Raman spectroscopy (SORS) provides chemical analysis at depth even when obscuring barriers such as plastic or tissue are present. As the collection probe is moved further away from the point of laser excitation, scattered photons from deeper layers begin to dominate the acquired spectra, thus giving rise to through barrier detection. Here, we demonstrate the potential of conventional Raman (CR) and SORS for through barrier detection using handheld spectrometers. We report the collection of Raman signals from an ethanol solution through plastic at thicknesses of up to 21 mm using SORS in combination with multivariate analysis. SORS is compared to CR, where we also demonstrate impressive through barrier detection of ethanol at depths up to 9 mm. We also highlight the advantage of applying multivariate analysis for through barrier detection using CR or SORS, particularly when peaks with similar spectral features are present in both the barrier and analyte spectra. In addition, to the best of our knowledge, this is the first report of the assessment of the maximum level of through barrier detection using handheld CR and SORS instruments with a backscattering geometry.

Duncan Graham opened a general discussion of the paper by Pavel Matousek: Regarding the temperature measurements, how did you do them? Stokes/anti-Stokes measurement? The values are not what I'd expect and seem lower. What was the wavelength and power of the laser and did you calculate what you thought the temperature measurement should be based on that? How far does the temperature gradient reach? The scattering absorption ration changes with nanoparticle size and composition. Have you thought about using more highly absorbing nanoparticles such as hollow gold nanoshells?

Resonant chalcogenpyrylium nanotags demonstrate an exceptional surface enhanced Raman scattering (SERS) performance for use in SORS applications. Using surface enhanced spatially offset Raman spectroscopy (SESORS), nanotags modified with a chalcogenpyrylium dye were observed at concentrations as low as 1 pM through 5 mm of tissue. Calculated limits of detection suggest that these SERS nanotags can be detected at 104 fM using surface enhanced spatially offset resonance Raman scattering (SESORRS) demonstrating their potential for in vivo applications.

Between 1969 and 1977, eleven semisubmersible drilling platforms were designed and built with an innovative pentagon shaped hull, specifically to work in the harsh environment of the North Sea. One of the drilling rigs, the Alexander L. Kielland, was converted soon after construction into an accommodation platform (flotel) and failed catastrophically in 1980. Another, the Pentagon 83 “Drillmaster” (renamed as Buchan Alpha), was being converted to a Floating Production Unit at the time of the disaster. The structure of Buchan Alpha was significantly modified during the conversion of the platform so that it benefited from the lessons learnt following the Alexander L. Kielland accident to ensure that the same sequence of events could not be repeated. This technical paper objective is to explain the integrated decommissioning process of the Buchan Alpha in the UK after more than 40 years since being built and more than 35 years of successful operation since it was converted to a Floating Production Unit, and how the features of its original design have accompanied the platform through the decommissioning process. The scope covers all phases of Buchan Alpha decommissioning from the detailed planning and preparation, the suspension of production up to the dismantling and recycling process. Significant challenges for the decommissioning team included the requirement to preserve the operational status of the subsea infrastructure for potential future field redevelopment and the diver disconnection of the subsea wells. Buchan Alpha’s deep draught presented limitations on the selection of dismantling and recycling yards due to quayside water depths. Complex ballasting operations and removal of the thruster’s propellers were required to facilitate the platform berthing at the quayside. Key lessons learned applicable for future decommissioning of floating production facilities will be shared.

To accurately predict atherosclerotic plaque progression, a detailed phenotype of the lesion at the molecular level is required. Here, we assess the respective merits and limitations of molecular imaging tools. Clinical imaging includes contrast-enhanced ultrasound (CEUS), an inexpensive and non-toxic technique but with poor sensitivity. Computed tomography (CT) benefits from high spatial resolution but poor sensitivity coupled with an increasing radiation burden that limits multiplexing. Despite high sensitivity, positron emission tomography (PET) and single-photon emission tomography (SPECT) have disadvantages when applied to multiplex molecular imaging due to poor spatial resolution, signal cross talk and increasing radiation dose. In contrast, magnetic resonance imaging (MRI) is non-toxic, displays good spatial resolution but poor sensitivity. Pre-clinical techniques include near-infrared fluorescence (NIRF), which provides good spatial resolution and sensitivity; however, multiplexing with NIRF is limited, due to photobleaching and spectral overlap. Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy are label-free techniques that detect molecules based on the vibrations of chemical bonds. Both techniques offer fast acquisition times with Raman showing superior spatial resolution. Raman signals are inherently weak; however, leading to the development of surface-enhanced Raman spectroscopy (SERS) that offers greatly increased sensitivity due to utilising metallic nanoparticles that can be functionalised with biomolecules targeted against plaque ligands while offering high multiplexing potential. This asset combined with high spatial resolution makes SERS an exciting prospect as a diagnostic tool. The ongoing refinements of SERS technologies such as deep tissue imaging and portable systems making SERS a realistic prospect for translation to the clinic.

Surface enhanced Raman scattering (SERS) tags are in situ probes that can provide sensitive and selective probes for optical analysis in biological materials. Engineering tags for use in the near infrared (NIR) region is of particular interest since there is an uncongested spectral window for optical analysis due to the low background absorption and scattering from many molecules. An improved synthesis has resulted in the formation of hollow gold nanoshells (HGNs) with a localised surface plasmon resonance (LSPR) between 800 and 900 nm which provide effective SERS when excited at 1064 nm. Seven Raman reporters containing aromatic amine or thiol attachment groups were investigated. All were effective but 1,2-bis(4-pyridyl)ethylene (BPE) and 4,4-azopyridine (AZPY) provided the largest enhancement. At approximately monolayer coverage, these two reporters appear to pack with the main axis of the molecule perpendicular or nearly perpendicular to the surface giving strong SERS and thus providing effective 1064 nm gold SERS nanotags.

This is the first report of the use of a hand-held 1064 nm Raman spectrometer combined with red-shifted surface-enhanced Raman scattering (SERS) nanotags to provide an unprecedented performance in the short-wave infrared (SWIR) region. A library consisting of 17 chalcogenopyrylium nanotags produce extraordinary SERS responses with femtomolar detection limits being obtained using the portable instrument. This is well beyond previous SERS detection limits at this far red-shifted wavelength and opens up new options for SERS sensors in the SWIR region of the electromagnetic spectrum (between 950 and 1700 nm).

NoC-based designs provide a scalable and flexible communication solution for the rising number of processing cores on a single chip. To master the complexity of the software design in such a NoC-based multi-core architecture, advanced incremental integration testing solutions are required. This work presents a virtual platform based software testing and debugging approach for a synchronous application model on a NoC-based designs provide a scalable and flexible communication solution for the rising number of processing cores on a single chip. To master the complexity of the software design in such a NoC-based multi-core architecture, advanced incremental integration testing solutions are required. This work presents a virtual platform based software testing and debugging approach for a synchronous application model on a 2x2 NoC-based MPSoC. We propose a development approach and a test environment that exploits the time approximation within Imperas OVP instruction accurate simulator and a functional model of the Nostrum NoC, for both software instructions and hardware clock cycles at larger time stamps called Quantum that does not sacrifice functional correctness. The functional testing environment runs the target software without running it on the real hardware platform. With the help of Nostrum NoC we can support a synchronous system execution that is reasonably fast and precise with respect to a global synchronization signal, called HeartBeat. As work in progress, this work also discusses several possible timing refinement and their possible implication on the simulation semantics and performance and how it is tackled in the future work. NoC-based MPSoC. We propose a development approach and a test environment that exploits the time approximation within Imperas OVP instruction accurate simulator and a functional model of the Nostrum NoC, for both software instructions and hardware clock cycles at larger time stamps called Quantum that does not sacrifice functional correctness. The functional testing environment runs the target software without running it on the real hardware platform. With the help of Nostrum NoC we can support a synchronous system execution that is reasonably fast and precise with respect to a global synchronization signal, called HeartBeat. As work in progress, this work also discusses several possible timing refinement and their possible implication on the simulation semantics and performance and how it is tackled in the future work.

Today's Cyber-Physical Systems (CPS) are witnessing a growing complexity in terms of the number of components and computational power in order to meet the requirements of nowadays applications. For this reason and due to their energy efficiency, Multiprocessor system-on-chips (MPSoC) are becoming ubiquitous. Yet, since these systems are often used in battery-driven and/or small housing use cases, the correct configuration of their power management techniques is an important factor in system design and can be related to possible safety aspects of the system. This calls for an adequate test framework, which is able to observe the power management functionalities of CPS, even before the actual hardware platform is available. The use of virtual platforms for functional validation, that allows executing the CPS's real target platform compatible application binary code on a generic host computer, is currently being adopted by the industry. This work focuses on enhancing industrial OVP virtual platforms by a functional test framework of the power management techniques. We will demonstrate and evaluate how this framework maintains to observe the power management techniques of the system under test. The evaluation uses a Xilinx ZC702 board based on a Xilinx Zynq-7000MPSoC and its correspondent virtual platform in OVP. Results show that the functional test framework is able to analyze the different modes of operation regarding the power management techniques of the Xilinx Zynq processing system.

Single DNA-nanoparticle binding is used to couple the plasmonic fields of nanophotonic bowtie dimers. The binding event is engineered to tune the resonance peak of the bowtie to correspond with a 633 nm laser. Surface enhanced Raman spectroscopy is performed on an individual bowtie, showing that a single DNA-nanoparticle binding event can be recorded.

The increasing popularity of surface plasmon resonance (SPR) and surface enhanced Raman scattering (SERS) sensor design based on nanotriangle or nanohole arrays, and the possibility to manufacture substrates at the transition between these plasmonic substrates, makes them ideal candidates for the establishment of structure-property relationships. This work features near diffraction-limited Raman images and FDTD simulations of nanotriangle and nanohole arrays substrates, which clearly demonstrate that the localization of the hot spot on these SERS substrates is significantly influenced by the ratio of diameter/periodicity (D/P). The experimental and simulation data reveal that the hot spots are located around nanotriangles (D/P = 1), characteristic of localized SPR. Decreasing the D/P ratio to 0.75-0.7 led to the creation of nanohole arrays, which promoted the excitation of a propagating surface plasmon (SP) delocalized over the metal network. The optimal SERS intensity was consistently achieved at this transition from nanotriangles to nanoholes, for every periodicity (650 nm to 1.5 μm) and excitation wavelength (633 and 785 nm) investigated, despite the presence or absence of a plasmonic band near the laser excitation. Further decreasing the D/P ratio led to excitation of a localized SP located around the rim of nanohole arrays for D/P of 0.5-0.6, in agreement with previous reports. In addition, this manuscript provides the first evidence that the hot spots are positioned inside the hole for D/P of 0.4, with the center being the region of highest electric field and Raman intensity. The compelling experimental evidence and FDTD simulations offer an overall understanding of the plasmonic properties of nanohole arrays as SERS and SPR sensors, which is of significant value in advancing the diversity of applications from such surfaces.

Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) can provide positive identification of an analyte or an analyte mixture with high sensitivity and selectivity. Better understanding of the theory and advances in the understanding of the practice have led to the development of practical applications in which the unique advantages of SERS/SERRS have been used to provide effective solutions to difficult analytical problems. This review presents a basic theory and illustrates the way in which SERS/SERRS has been developed for practical use.

The detection of subclinical early inflammation in autoimmune diseases is an important but currently technically demanding approach to direct initial diagnosis and subsequent choice of therapy. Recent advances in imaging using NP provides the potential to detect cellular recruitment, vascular activation or leakage at a subclinically stage of disease and may provide predictive "biomarkers" of future pathogenesis. The NP used are either untargeted and taken up by phagocytic cells, or are linked to a ligand, targeting localisation to the site of inflammation. Techniques, varying from MRI and fluorescence to Raman spectroscopy are being employed. In this short review, we summarise many of the recent developments in the field of NP imaging related to inflammation.

Following years of development, electronic paper is now entering ebooks, mobile phones and signs, and, as Duncan Graham-Rowe reports, is starting to gain the market acceptance that it has long strived for.

Holographic disk drives have long promised to eclipse even the latest high-density optical storage media. Now finally, as Duncan Graham-Rowe reports, the promising three-dimensional approach to storing information is about to make its debut.

We report a versatile nanophotonic biosensing platform that enables both colorimetric detection and enhanced Raman spectroscopy detection of molecular binding events. Through the integration of electron-beam lithography, dip-pennanolithography and molecular self-assembly, we demonstrate plasmonic nanostructures which change geometry and plasmonic properties in response to molecularly-mediated nanoparticle binding events. These biologically-active nanostructured surfaces hold considerable potential for use as multiplexed sensor platforms for point-of-care diagnostics, and as scaffolds for a new generation of molecularly dynamic metamaterials. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Raman spectroscopy is a form of vibrational spectroscopy that is well suited to the molecular identification of a variety of analytes, including both explosives and biological agents. The technique has been gaining more widespread interest due to improvements in instrumentation, sensitivity, and its ease of use, in comparison to other techniques. In this paper, we describe recent advances in Raman spectroscopy with respect to the detection of high-energy explosives and biological materials. In particular, emphasis is placed on the exploitation of enhancement factors that overcome traditional limitations on sensitivity, namely, surface enhancement and resonance enhancement, functionalization of target analytes, and the use of novel lab-on-a-chip technology.

A neural network-based data analysis tool, developed to speed the damage detection process for the NDE of impact damaged carbon fibre composites, is discussed. A feature extraction method utilising a gradient threshold search function and a feed forward neural network for pattern recognition were used to develop the system. Impact damaged carbon composite sample plates were scanned with an eddy current-based NDE setup using HTS SQUID gradiometers and double-D excitation coils. Detection of damage sites in data affected by noise spikes caused by environmental disturbances is demonstrated. Finally, a possible design for a future entirely automated scanning system is also introduced.

Recent work with HTS SQUIDs in nondestructive evaluation has concentrated on the detection of flaws in aircraft-grade aluminum, with particular emphasis on surface-breaking tears beside rivets. More complex materials are now also being used in aircraft manufacture, with carbon fiber reinforced polymer (CFRP) being one of the most common. Existing technologies such as ultrasound are particularly well suited to the detection of impact-damaged sites and until now there have only been a few reports of eddy current examination of CFRP samples. Here we present results on samples with regions of heat damage, impact damage and with nonmagnetic inserts using eddy current detection techniques. We compare the signal to noise ratio and spatial resolution for a variety of sensors including HTS SQUIDs and gradiometers and conventional induction coils, and discuss variations in detection efficiency with field component measured.

With an ingredients list that includes rhino horn and tiger bone, traditional Asian medicine is on a collision course with wildlife preservation.

Modern living seems somehow to make our immune systems overly sensitive. Is cleanliness at fault — or something else?

The most controversial aspect of biofuels is the perceived competition for farmland. Will advances in biofuels and agriculture send this trade-off speeding towards the history books?

Vaccines have proved to be one of the most powerful and effective ways of reducing disease. However, if we are to maximize their impact on global health, then we need to develop new vaccines for additional diseases as well as to improve their supply and delivery, particularly in developing countries.

We report the manufacture of ordered silver and copper nanorod arrays for surface-enhanced Raman scattering using oblique angle deposition (OAD) on prepatterned polymer sheets. It was found that the patterned polymer substrate defined nucleation sites which guided subsequent growth of nanorods. Enhanced surface-enhanced Raman spectroscopy (SERS) intensities of the Raman probe molecule trans-1,2-bis(4-pyridyl)ethylene (BPE) were found for Ag arrays on polymer, up to about 10 times that of the Ag-silica control. The SERS response of Ag nanorod arrays of different structures was investigated alongside results obtained from discrete dipole approximation simulations. This revealed that narrow gaps between nanorods, formed by guided nucleation during OAD, were responsible for this dramatic enhancement. Ordered Cu nanorod arrays were also successfully fabricated, producing a SERS intensity about 3 times that of Cu on silicon for both BPE and another Raman probe - rhodamine B isothiocyanate (RBITC) - highlighting the potential of this large-scale, low-cost, SERS-active substrate.

Strain gauges that change colour when stressed, bright backlight-free displays and highly sensitive biological sensors are all potential applications of tunable photonic crystal materials, reports Duncan Graham-Rowe.

Photoacoustic imaging, using laser light to stimulate the emission of ultrasonic waves from tissue inside the human body, potentially offers a route to far deeper imaging than possible with conventional optical techniques, reports Duncan Graham-Rowe.

A visit to a dental clinic could cease to be a fearsome experience. Duncan Graham-Rowe finds out how lasers can help dentists to provide patients with more comfortable and convenient dental treatments.

Optical coherence tomography is rapidly becoming an important clinical tool, which provides high-resolution images that cannot be obtained by other means. Duncan Graham-Rowe spoke to a few of the companies developing the technology.

The idea of photovoltaic cells that can be printed onto thin, flexible plastic substrates are an enticing prospect for promoting solar energy generation. Duncan Graham-Rowe reports.

A growing number of enterprises around the world are now commercializing fibre Bragg grating sensors for sensing everything from temperature and pressure to vibration and strain. Duncan Graham-Rowe reports.

Imaging and spectroscopy equipment that exploits terahertz waves rather than visible or infrared light is now being developed by several firms around the world. Duncan Graham-Rowe spoke to a few of them to catch up with the latest developments.

Introduction to a themed issue which aims to provide a comprehensive and diverse overview of the latest developments in optical diagnosis.

Novel Ag on TiO2 films are generated by semiconductor photocatalysis and characterized by ultraviolet–visible (UV/Vis) spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM), as well as assessed for surface-enhanced Raman scattering (SERS) activity. The nature and thickness of the photo-deposited Ag, and thus the degree of SERS activity, is controlled by the time of exposure of the TiO2 film to UV light. All such films exhibit the optical characteristics (λmax ≅ 390 nm) of small (40 nm) Ag islands that grow and merge with increasing levels of Ag photodeposition. Tested with a benzotriazole dye probe, the films are SERS active, exhibiting activity similar to that of 6-nm-thick vapor-deposited films. The Ag/TiO2 films exhibit a lower residual standard deviation (∼25%) compared with Ag vapor-deposited films (∼45%), which is, however, still unacceptable for quantitative work. The sample-to-sample variance could be reduced significantly (2 films are mechanically robust and resistant to removal and damage by scratching, unlike the Ag vapor-deposited films. The Ag/TiO2 films also exhibit no obvious loss of SERS activity when stored in the dark under otherwise ambient conditions. The possible extension of this simple, effective method of producing Ag films for SERS, to metals other than Ag and to semiconductors other than TiO2, is briefly discussed.

Atherosclerosis is a complex inflammatory disease characterised by endothelial cell (EC) dysfunction, infiltration of macrophages into the vessel wall, and the formation of an atheroma. The surface of the atherosclerotic plaque is covered by a protective “fibrous cap” composed of ECs and smooth muscle cells (SMCs), with the interaction between ECs, SMCs and macrophages being crucial for plaque stability. We have now developed an in vitro model combining these key cell types in a three-dimensional co-culture system representative of the atheroma. Human coronary artery SMCs (CASMCs) were seeded on the underside of a 3 μm pored geltrex coated transwell insert, allowed to attach, and incubated in 6 well plates at 37C/5% CO 2 until confluent. Human coronary artery endothelial cells (HCAECs) were then seeded on the upper surface of the transwell membrane and cultured until confluent. Transwell inserts were then transferred to 6 well plates containing phorbol myristate acetate (PMA)-differentiated THP-1 macrophage-like cells. Immunohistochemical analysis of this model identified a confluent monolayer of ECs, a multilayer of SMCs segregated by the transwell insert membrane, and a population of macrophages. Isolation of these distinct cellular layers is a simple method for subsequent investigation by many techniques, including Flow Cytometry and Western Blot. The model described allows for the simultaneous analysis of multiple key cell types involved in atherosclerosis development, providing a useful research tool to be employed to monitor intercellular communication, cell migration dynamics, and stimulation. Supported by the Engineering and Physical Sciences Research Council (EPSRC) grant EP/L014165/1.

Surface enhanced resonance Raman scattering (SERRS) provides an increase in sensitivity over Raman scattering of about 1014 and rivals fluorescence in terms of its quantum efficiency. With the use of modern edge and notch filters and CCD cameras, the price and complexity of Raman spectroscopy equipment has decreased rapidly. This means that the potential advantages of SERRS are now much easier to release for use for practical purposes. The technique has specific advantages in terms of sensitivity and coding for use for tagging.

A commercially available fluorimeter with a white light source is used to detect surface enhanced resonance Raman scattering (SERRS). This approach allows facile tunability of the excitation source for SERRS.

Several new drugs for treating chronic obstructive pulmonary disease are about to hit the market, with more in the pipeline.

Text messages and voice recognition systems on your smart phones could get better if crowds are brought in to help