Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer

Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. Mass spectrometry (MS)-driven proteomics uniquely allows for the detection, identification and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review we describe applications of this technology in KLK biomarker discovery, and elucidate MS-based techniques which have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis and therapies.

Identifying factors that promote consumer behaviours causing expired domestic food waste

Many commentators argue that domestic food waste is strongly influenced by consumer behaviours. This article reports on a study using mixed-methods to identify key factors responsible for promoting consumer behaviours that lead to domestic food waste through the lens of the Value-Belief-Norm (VBN) theory. Based on the study’s findings, three factors are proposed that cause behaviours that lead to food waste: supply knowledge – does a consumer know what food they have available; location knowledge – does a consumer know where to locate food items, and; food literacy – to what degree do past experience and acquired knowledge impact on a consumer’s food consumption and wastage practices. We analyse the study’s findings in light of a review of literature about consumer food wastage behaviours and in turn, present new insights into consumer behaviour, food waste, and the use of technology to reduce food waste.

UbiOpticon : participatory sousveillance with urban screens and mobile phone cameras

In many cities around the world, surveillance by a pervasive net of CCTV cameras is a common phenomenon in an attempt to uphold safety and security across the urban environment. Video footage is being recorded and stored, sometimes live feeds are being watched in control rooms hidden from public access and view. In this study, we were inspired by Steve Mann’s original work on sousveillance (surveillance from below) to examine how a network of camera equipped urban screens could allow the residents of Oulu in Finland to collaborate on the safekeeping of their city. An agile, rapid prototyping process led to the design, implementation and ‘in the wild’ deployment of the UbiOpticon screen application. Live video streams captured by web cams integrated at the top of 12 distributed urban screens were broadcast and displayed in a matrix arrangement on all screens. The matrix also included live video streams of two roaming mobile phone cameras. In our field study we explored the reactions of passers-by and users of this screen application that seeks to inverse Bentham’s original panopticon by allowing the watched to be watchers at the same time. In addition to the original goal of participatory sousveillance, the system’s live video feature sparked fun and novel user-led apprlopriations.

Vote with your feet : local community polling on urban screens

Falling prices have led to an ongoing spread of public displays in urban areas. Still, they mostly show passive content such as commercials and digital signage. At the same time, technological advances have enabled the creation of interactive displays potentially increasing their attractiveness for the audience, e.g. through providing a platform for civic discourse. This poses considerable challenges, since displays need to communicate the opportunity to engage, motivate the audience to do so, and be easy to use. In this paper we present Vote With Your Feet, a hyperlocal public polling tool for urban screens allowing users to express their opinions. Similar to vox populi interviews on TV or polls on news websites, the tool is meant to reflect the mindset of the community on topics such as current affairs, cultural identity and local matters. It is novel in that it focuses on a situated civic discourse and provides a tangible user interface, tackling the mentioned challenges. It shows one Yes/No question at a time and enables users to vote by stepping on one of two tangible buttons on the ground. This user interface was introduced to attract people’s attention and to lower participation barriers. Our field study showed that Vote With Your Feet is perceived as inviting and that it can spark discussions among co-located people.

Using communicative ecology theory to scope the emerging role of social media in the evolution of urban food systems

Urban agriculture plays an increasingly vital role in supplying food to urban populations. Changes in Information and Communications Technology (ICT) are already driving widespread change in diverse food-related industries such as retail, hospitality and marketing. It is reasonable to suspect that the fields of ubiquitous technology, urban informatics and social media equally have a lot to offer the evolution of core urban food systems. We use communicative ecology theory to describe emerging innovations in urban food systems according to their technical, discursive and social components. We conclude that social media in particular accentuate fundamental social interconnections normally effaced by conventional industrialised approaches to food production and consumption.

Treatment plan complexity metrics for predicting IMRT pre-treatment quality assurance results

The planning of IMRT treatments requires a compromise between dose conformity (complexity) and deliverability. This study investigates established and novel treatment complexity metrics for 122 IMRT beams from prostate treatment plans. The Treatment and Dose Assessor software was used to extract the necessary data from exported treatment plan files and calculate the metrics. For most of the metrics, there was strong overlap between the calculated values for plans that passed and failed their quality assurance (QA) tests. However, statistically significant variation between plans that passed and failed QA measurements was found for the established modulation index and for a novel metric describing the proportion of small apertures in each beam. The ‘small aperture score’ provided threshold values which successfully distinguished deliverable treatment plans from plans that did not pass QA, with a low false negative rate.

The effect of very small air gaps on small field dosimetry

The purpose of this study was to investigate the effect of very small air gaps (less than 1 mm) on the dosimetry of small photon fields used for stereotactic treatments. Measurements were performed with optically stimulated luminescent dosimeters (OSLDs) for 6 MV photons on a Varian 21iX linear accelerator with a Brainlab lMLC attachment for square field sizes down to 6 mm 9 6 mm. Monte Carlo simulations were performed using EGSnrc C++ user code cavity. It was found that the Monte Carlo model used in this study accurately simulated the OSLD measurements on the linear accelerator. For the 6 mm field size, the 0.5 mm air gap upstream to the active area of the OSLD caused a 5.3 % dose reduction relative to a Monte Carlo simulation with no air gap...

Development of a dose assessment tool for the auditing of radiotherapy treatment dosimetric quality

The reporting and auditing of patient dose is an important component of radiotherapy quality assurance. The manual extraction of dose-volume metrics is time consuming and undesirable when auditing the dosimetric quality of a large cohort of patient plans. A dose assessment application was written to overcome this, allowing the calculation of various dose-volume metrics for large numbers of plans exported from treatment planning systems. This application expanded on the DICOM-handling functionality of the MCDTK software suite. The software extracts dose values in the volume of interest by using a ray casting point-in-polygon algorithm, where the polygons have been defined by the contours in the RTSTRUCT file...

Three-dimensional dose verification for clinical treatments of small intracranial tumours

Cancers of the brain and central nervous system account for 1.6% of new cancers and 1.8% of cancer deaths globally. The highest rates of all developed nations are observed in Australia and New Zealand. There are known complexities associated with dose measurement of very small radiation fields. Here, 3D dosimetric verification of treatments for small intracranial tumours using gel dosimetry was investigated.

Phosphorus-based functional groups as hydrogen bonding templates for rotaxane formation

We report on the use of the hydrogen bond acceptor properties of some phosphorus-containing functional groups for the assembly of a series of [2]rotaxanes. Phosphinamides, and the homologous thio– and selenophosphinamides, act as hydrogen bond acceptors that, in conjunction with an appropriately positioned amide group on the thread, direct the assembly of amide-based macrocycles around the axle to form rotaxanes in up to 60% yields. Employing solely phosphorus-based functional groups as the hydrogen bond accepting groups on the thread, a bis(phosphinamide) template and a phosphine oxide-phosphinamide template afforded the corresponding rotaxanes in 18 and 15 % yields, respectively. X-Ray crystallography of the rotaxanes shows the presence of up to four intercomponent hydrogen bonds between the amide groups of the macrocycle and various hydrogen bond accepting groups on the thread, including rare examples of amide-to-phosphonamide, -thiophosphinamide and -selenophosphinamide groups. With a phosphine oxide-phosphinamide thread, the solid state structure of the rotaxane is remarkable, featuring no direct intercomponent hydrogen bonds but rather a hydrogen bond network involving water molecules that bridge the H-bonding groups of the macrocycle and thread through bifurcated hydrogen bonds. The incorporation of phosphorus-based functional groups into rotaxanes may prove useful for the development of molecular shuttles in which the macrocycle can be used to hinder or expose binding ligating sites for metal-based catalysts.

Contact with existing adipose tissue is inductive for adipogenesis in matrigel

The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft (p < 0.01). Autografts with 1 mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

The role of biological extracellular matrix scaffolds in vascularized three-dimensional tissue growth in vivo

An in vivo murine vascularized chamber model has been shown to generate spontaneous angiogenesis and new tissue formation. This experiment aimed to assess the effects of common biological scaffolds on tissue growth in this model. Either laminin-1, type I collagen, fibrin glue, hyaluronan, or sea sponge was inserted into silicone chambers containing the epigastric artery and vein, one end was sealed with adipose tissue and the other with bone wax, then incubated subcutaneously. After 2, 4, or 6 weeks, tissue from chambers containing collagen I, fibrin glue, hyaluronan, or no added scaffold (control) had small amounts of vascularized connective tissue. Chambers containing sea sponge had moderate connective tissue growth together with a mild "foreign body" inflammatory response. Chambers containing laminin-1, at a concentration 10-fold lower than its concentration in Matrigel™, resulted in a moderate adipogenic response. In summary, (1) biological hydrogels are resorbed and gradually replaced by vascularized connective tissue; (2) sponge-like matrices with large pores support connective tissue growth within the pores and become encapsulated with granulation tissue; (3) laminin-containing scaffolds facilitate adipogenesis. It is concluded that the nature and chemical composition of the scaffold exerts a significant influence on the amount and type of tissue generated in this in vivo chamber model.

The influence of extracellular matrix on the generation of vascularized, engineered, transplantable tissue

In a recently described model for tissue engineering, an arteriovenous loop comprising the femoral artery and vein with interposed vein graft is fabricated in the groin of an adult male rat, placed inside a polycarbonate chamber, and incubated subcutaneously. New vascularized granulation tissue will generate on this loop for up to 12 weeks. In the study described in this paper three different extracellular matrices were investigated for their ability to accelerate the amount of tissue generated compared with a no-matrix control. Poly-D,L-lactic-co-glycolic acid (PLGA) produced the maximal weight of new tissue and vascularization and this peaked at two weeks, but regressed by four weeks. Matrigel was next best. It peaked at four weeks but by eight weeks it also had regressed. Fibrin (20 and 80 mg/ml), by contrast, did not integrate with the generating vascularized tissue and produced less weight and volume of tissue than controls without matrix. The limiting factors to growth appear to be the chamber size and the capacity of the neotissue to integrate with the matrix. Once the sides of the chamber are reached or tissue fails to integrate, encapsulation and regression follow. The intrinsic position of the blood supply within the neotissue has many advantages for tissue and organ engineering, such as ability to seed the construct with stem cells and microsurgically transfer new tissue to another site within the individual. In conclusion, this study has found that PLGA and Matrigel are the best matrices for the rapid growth of new vascularized tissue suitable for replantation or transplantation.