EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer

PURPOSE: EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear.

EXPERIMENTAL DESIGN: EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models.

RESULTS: Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells.

CONCLUSIONS: These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. Clin Cancer Res; 22(1); 230-42. ©2015 AACR.

Following instructions in a virtual school: Does working memory play a role?

Accumulating evidence that working memory supports the ability to follow instructions has so far been restricted to experimental paradigms that have greatly simplified the practical demands of performing actions to instructions in everyday tasks. The aim of the present study was to investigate whether working memory is involved in maintaining information over the longer periods of time that are more typical of everyday situations that require performing instructions to command. Forty-two children 7–11 years of age completed assessments of working memory, a real-world following-instructions task employing 3-D objects, and two new computerized instruction-following tasks involving navigation around a virtual school to complete a sequence of practical spoken commands. One task involved performing actions in a single classroom, and the other, performing actions in multiple locations in a virtual school building. Verbal working memory was closely linked with all three following-instructions paradigms, but with greater association to the virtual than to the real-world tasks. These results indicate that verbal working memory plays a key role in following instructions over extended periods of activity.

The EU Clinical Trials Regulation: Key Priorities, Purposes and Aims and the Implications for Public Health

The replacement of the European Union (EU) Clinical Trials Directive by the new Clinical Trials Regulation (CTR), which entered into force on 16 June 2014 but will not apply before 28 May 2016, provides an opportunity to review the legal and political context within which this important aspect of research law and policy sits and to reflect on the implications for public health. My aim in this article is to relate the context to the key purposes and aims of EU law and policy on clinical trials in order to explain and clarify its orientation. On that basis, I argue that the CTR and the changes it introduces to the law on clinical trials are part of the EU's continued focus on market optimisation. It is this focus that orients and directs the wider pharmaceutical development pipeline, but that undermines the achievement of key public health objectives.

Secure key generation from OFDM subcarriers' channel responses

The ability to exchange keys between users is vital in any wireless based security system. A key generation technique which 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 frequency-division 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.

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.

Beyond managerial talent: ‘key group’ identification and differential compensation practices in multinational companies

With the maturation of strategic human resource management scholarship, there appears to be a greater call to move from monolithic workforce management to a more strategic and differentiated emphasis on employees with the greatest capacity to enhance competitive advantage. There has been little consideration in the literature as to whether organizations formally identify key groups of employees based on their impact on organizational learning and core competences. Using survey evidence from 260 multinational companies (MNCs), this paper explores the extent to which key groups of employees are formally recognized and whether they are subject to differential compensation practices. The results demonstrate that just in excess of half of these MNCs identify a key group. There was considerable differentiation in the compensation practices between these key groups, managers and the largest occupational group in the workforce. The results give rise to questions worthy of future investigation, namely whether the differentiated approaches used lead to improved performance outcomes.

Efficient Key Generation by Exploiting Randomness from Channel Responses of Individual OFDM Subcarriers

Key generation from the randomness of wireless channels is a promising technique to establish a secret cryptographic key securely between legitimate users. This paper proposes a new approach to extract keys efficiently from channel responses of individual orthogonal frequency-division multiplexing (OFDM) subcarriers. The efficiency is achieved by (i) fully exploiting randomness from time and frequency domains and (ii) improving the cross-correlation of the channel measurements. Through the theoretical modelling of the time and frequency autocorrelation relationship of the OFDM subcarrier's channel responses, we can obtain the optimal probing rate and use multiple uncorrelated subcarriers as random sources. We also study the effects of non-simultaneous measurements and noise on the cross-correlation of the channel measurements. We find the cross-correlation is mainly impacted by noise effects in a slow fading channel and use a low pass filter (LPF) to reduce the key disagreement rate and extend the system's working signal-to-noise ratio range. The system is evaluated in terms of randomness, key generation rate, and key disagreement rate, verifying that it is feasible to extract randomness from both time and frequency domains of the OFDM subcarrier's channel responses.

Key Generation from Wireless Channels: A Review

Key generation from the randomness of wireless channels is a promising alternative to public key cryptography for the establishment of cryptographic keys between any two users. This paper reviews the current techniques for wireless key generation. The principles, performance metrics and key generation procedure are comprehensively surveyed. Methods for optimizing the performance of key generation are also discussed. Key generation applications in various environments are then introduced along with the challenges of applying the approach in each scenario. The paper concludes with some suggestions for future studies.

Verification of Key Generation from Individual OFDM Subcarrier's Channel Response

This paper presents a key generation system derived from the channel response of individual subcarrier in orthogonal frequency-division multiplexing (OFDM) systems. Practical aspects of the security were investigated by implementing our key generation scheme on a wireless open-access research platform (WARP), which enables us to obtain channel estimation of individual OFDM subcarriers, a feature not currently available in most commercial wireless interface cards. Channel response of individual OFDM subcarrier is usually a wide sense stationary random process, which allows us to find the optimal probing period and maximize the key generation rate. The implementation requires cross layer design as it involves interaction between physical and MAC layer. We have experimentally verified the feasibility and principles of key generation, and also evaluated the performance of our system in terms of randomness, key generation rate and key disagreement rate, which proves that OFDM subcarrier's channel responses are valid for key generation.

Experimental Study on Channel Reciprocity in Wireless Key Generation

Key generation from wireless channels is a promising alternative to public key cryptography for the establishment of cryptographic keys. It is the first paper to experimentally study the channel reciprocity principle of key generation, through investigating and quantifying channel measurements' cross-correlation relationship affected by noise and non-simultaneous measurements. Channel measurements, both received signal strength and channel state information, are collected from a real experimental platform using the wireless open access research platform (WARP) in a multipath office room. We found that in a slow fading channel (e.g., with a coherence time of about 50~ms), the channel cross-correlation is impacted greatly by noise but little by non-simultaneous measurements with a small sampling time difference (e.g., 0.06 ms). The resolution of the sampling time difference can be satisfied by wireless systems such as IEEE 802.11 to maintain an acceptable cross-correlation coefficient without affecting the bandwidth and communication efficiency.