AXL Is a Key Regulator of Inherent and Chemotherapy-Induced Invasion and Predicts a Poor Clinical Outcome in Early-Stage Colon Cancer

Purpose: Despite the use of 5-fluorouracil (5-FU)–based adjuvant treatments, a large proportion of patients with high-risk stage II/III colorectal cancer will relapse. Thus, novel therapeutic strategies are needed for early-stage colorectal cancer. Residual micrometastatic disease from the primary tumor is a major cause of patient relapse.

Experimental Design: To model colorectal cancer tumor cell invasion/metastasis, we have generated invasive (KRASMT/KRASWT/+chr3/p53-null) colorectal cancer cell subpopulations. Receptor tyrosine kinase (RTK) screens were used to identify novel proteins that underpin the migratory/invasive phenotype. Migration/invasion was assessed using the XCELLigence system. Tumors from patients with early-stage colorectal cancer (N = 336) were examined for AXL expression.

Results: Invasive colorectal cancer cell subpopulations showed a transition from an epithelial-to-mesenchymal like phenotype with significant increases in migration, invasion, colony-forming ability, and an attenuation of EGF receptor (EGFR)/HER2 autocrine signaling. RTK arrays showed significant increases in AXL levels in all invasive sublines. Importantly, 5-FU treatment resulted in significantly increased migration and invasion, and targeting AXL using pharmacologic inhibition or RNA interference (RNAi) approaches suppressed basal and 5-FU–induced migration and invasion. Significantly, high AXL mRNA and protein expression were found to be associated with poor overall survival in early-stage colorectal cancer tissues.

Conclusions: We have identified AXL as a poor prognostic marker and important mediator of cell migration/invasiveness in colorectal cancer. These findings provide support for the further investigation of AXL as a novel prognostic biomarker and therapeutic target in colorectal cancer, in particular in the adjuvant disease in which EGFR/VEGF–targeted therapies have failed.

An exploration of business model development in the commercialization of technology innovations

Research on business model development has focused on the relationships between elements of value conceptualization and organization having a linear sequence in which business models are first designed and then implemented. Another stream of research points to business model development with these elements interacting in a cyclical manner. There is a need to improve our understanding of the connective mechanisms and dynamics involved in business model development, particularly from the challenging perspective of commercializing innovations. The aim of this paper was to explore business model development during the commercialization of innovations through a case-based qualitative study. This study found from four case studies that specific elements of business model development, representative of the conceptualization of value and organizing for value creation, integrate in a dynamic and cyclical process in the commercialization of technology innovations. The study provides empirical evidence that adds new insights to literature on sequential and more interactive processes of business model development. It also contributes to literature on business model development and particularly how it relates to the commercialization of innovations.

Loss of Synaptic Connectivity, Particularly in Second Order Neurons Is a Key Feature of Diabetic Retinal Neuropathy in the Ins2Akita Mouse

Retinal neurodegeneration is a key component of diabetic retinopathy (DR), although the detailed neuronal damage remains ill-defined. Recent evidence suggests that in addition to amacrine and ganglion cell, diabetes may also impact on other retinal neurons. In this study, we examined retinal degenerative changes in Ins2^Akita diabetic mice. In scotopic electroretinograms (ERG), b-wave and oscillatory potentials were severely impaired in 9-month old Ins2^Akita mice. Despite no obvious pathology in fundoscopic examination, optical coherence tomography (OCT) revealed a progressive thinning of the retina from 3 months onwards. Cone but not rod photoreceptor loss was observed in 3-month-old diabetic mice. Severe impairment of synaptic connectivity at the outer plexiform layer (OPL) was detected in 9-month old Ins2Akita mice. Specifically, photoreceptor presynaptic ribbons were reduced by 25% and postsynaptic boutons by 70%, although the density of horizontal, rod- and cone-bipolar cells remained similar to non-diabetic controls. Significant reductions in GABAergic and glycinergic amacrine cells and Brn3a+ retinal ganglion cells were also observed in 9-month old Ins2^Akita mice. In conclusion, the Ins2^Akita mouse develops cone photoreceptor degeneration and the impairment of synaptic connectivity at the OPL, predominately resulting from the loss of postsynaptic terminal boutons. Our findings suggest that the Ins2^Akita mouse is a good model to study diabetic retinal neuropathy.

How much do you need: a randomised experiment of whether readers can understand the key messages from summaries of Cochrane Reviews, without reading the full review?

Objective: We explored whether readers can understand key messages without having to read the full review, and if there were differences in understanding between various types of summary.
Design: A randomised experiment of review summaries which compared understanding of a key outcome.
Participants: Members of university staff (n = 36).
Setting: Universities on the island of Ireland.
Method: The Cochrane Review chosen examines the health impacts of the use of electric fans during heat waves. Participants were asked their expectation of the effect these would have on mortality. They were then randomly assigned a summary of the review (i.e. abstract, plain language summary, podcast or podcast transcription) and asked to spend a short time reading/listening to the summary. After this they were again asked about the effects of electric fans on mortality and to indicate if they would want to read the full Review.
Main outcome measure: Correct identification of a key review outcome.
Results: Just over half (53%) of the participants identified its key message on mortality after engaging with their summary. The figures were 33% for the abstract group, 50% for both the plain language and transcript groups and 78% for the podcast group.
Conclusions: The differences between the groups were not statistically significant but suggest that the audio summary might improve knowledge transfer compared to written summaries. These findings should be explored further using a larger sample size and with other reviews.

Key Players and Key Groups in Teams

This paper contributes to the literature on centrality measures in economics by defining a team game and identifying the key players and key groups
in the game. We extend the work of Ballester et al. (Econometrica, 2006) by incorporating a network outcome component in the players' payoff functions and prove that there is a unique interior Nash Equilibrium in pure strategies. We develop a team intercentrality measure based on alternative scenarios that capture the externality created by teammates on each player.

Does wave exposure determine the interactive effects of losing key grazers and ecosystem engineers?

The consequences of biodiversity loss in the face of environmental change remain difficult to predict, given the complexity of interactions among species and the context-dependency of their functional roles within ecosystems. Predictions may be enhanced by studies testing how the interactive effects of species loss from different functional groups vary with important environmental drivers. On rocky shores, limpets and barnacles are recognised as key grazers and ecosystem engineers, respectively. Despite the large body of research examining the combined effects of limpet and barnacle removal, it is unclear how their relative importance varies according to wave exposure, which is a dominant force structuring intertidal communities. We tested the responses of algal communities to the removal of limpets and barnacles on three sheltered and three wave-exposed rocky shores on the north coast of Ireland. Limpet removal resulted in a relative increase in microalgal biomass on a single sheltered shore only, but led to the enhanced accumulation of ephemeral macroalgae on two sheltered shores and one exposed shore. On average, independently of wave exposure or shore, ephemeral macroalgae increased in response to limpet removal, but only when barnacles were removed. On two sheltered shores and one exposed shore, however, barnacles facilitated the establishment of fucoid macroalgae following limpet removal. Therefore, at the scale of this study, variability among individual shores was more important than wave exposure per se in determining the effect of limpet removal and its interaction with that of barnacles. Overall, these findings demonstrate that the interactive effects of losing key species from different functional groups may not vary predictably according to dominant environmental factors.

Secure Key Generation from OFDM Subcarriers’ Channel Response

The ability to exchange keys between users is vital in any wireless based security system. A key generation technique exploits the randomness of the wireless channel is a promising alternative to existing key distribution techniques, e.g., public key cryptography. In this paper a secure key generation scheme based on the subcarriers’ channel responses in orthogonal frequencydivision multiplexing (OFDM) systems is proposed. We first implement a time-variant multipath channel with its channel impulse response modelled as a wide sense stationary (WSS) uncorrelated scattering random process and demonstrate that each subcarrier’s channel response is also a WSS random process. We then define the X% coherence time as the time required to produce an X% correlation coefficient in the autocorrelation function (ACF) of each channel tap, and find that when all the channel taps have the same Doppler power spectrum, all subcarriers’ channel responses has the same ACF as the channel taps. The subcarrier’s channel response is then sampled every X% coherence time and quantized into key bits. All the key sequences’ randomness is tested using National Institute of Standards and Technology (NIST) statistical test suite and the results indicate that the commonly used sampling interval as 50% coherence time cannot guarantee the randomness of the key sequence.

Key performance indicators – A new approach for specifying concrete and assessing state of health of concrete structure

The focus of this paper is to outline a method for consolidating and implementing the work on performance-based specification and testing. First part of the paper will review the mathematical significance of the variables used in common service life models. The aim is to identify a set of significant variables that influence the ingress of chloride ions into concrete. These variables are termed as Key Performance Indicators (KPI’s). This will also help to reduce the complexity of some of the service life models and make them more appealing for practicing engineers. The second part of the paper presents a plan for developing a database based on these KPI’s so that relationships can then be drawn between common concrete mix parameters and KPI’s. This will assist designers in specifying a concrete with adequate performance for a particular environment. This, collectively, is referred to as the KPI based approach and the concluding remarks will outline how the authors envisage the KPI theory to relate to performance assessment and monitoring.