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.

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.

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.

Lattice-based Encryption Over Standard Lattices in Hardware

Lattice-based cryptography has gained credence recently as a replacement for current public-key cryptosystems, due to its quantum-resilience, versatility, and relatively low key sizes. To date, encryption based on the learning with errors (LWE) problem has only been investigated from an ideal lattice standpoint, due to its computation and size efficiencies. However, a thorough investigation of standard lattices in practice has yet to be considered. Standard lattices may be preferred to ideal lattices due to their stronger security assumptions and less restrictive parameter selection process. In this paper, an area-optimised hardware architecture of a standard lattice-based cryptographic scheme is proposed. The design is implemented on a FPGA and it is found that both encryption and decryption fit comfortably on a Spartan-6 FPGA. This is the first hardware architecture for standard lattice-based cryptography reported in the literature to date, and thus is a benchmark for future implementations.
Additionally, a revised discrete Gaussian sampler is proposed which is the fastest of its type to date, and also is the first to investigate the cost savings of implementing with lamda_2-bits of precision. Performance results are promising in comparison to the hardware designs of the equivalent ring-LWE scheme, which in addition to providing a stronger security proof; generate 1272 encryptions per second and 4395 decryptions per second.

Power Spectral Density Side-Channel Attack Overlapping Window Method

Cryptographic algorithms have been designed to be computationally secure, however it has been shown that when they are implemented in hardware, that these devices leak side channel information that can be used to mount an attack that recovers the secret encryption key. In this paper an overlapping window power spectral density (PSD) side channel attack, targeting an FPGA device running the Advanced Encryption Standard is proposed. This improves upon previous research into PSD attacks by reducing the amount of pre-processing (effort) required. It is shown that the proposed overlapping window method requires less processing effort than that of using a sliding window approach, whilst overcoming the issues of sampling boundaries. The method is shown to be effective for both aligned and misaligned data sets and is therefore recommended as an improved approach in comparison with existing time domain based correlation attacks.

Variable Window Power Spectral Density Attack

Side channel attacks permit the recovery of the secret key held within a cryptographic device. This paper presents a new EM attack in the frequency domain, using a power spectral density analysis that permits the use of variable spectral window widths for each trace of the data set and demonstrates how this attack can therefore overcome both inter-and intra-round random insertion type countermeasures. We also propose a novel re-alignment method exploiting the minimal power markers exhibited by electromagnetic emanations. The technique can be used for the extraction and re-alignment of round data in the time domain.

Computerized key to the genus Bursaphelenchus Fuchs, analysis of species clusters based on morphology, using information of insect vectors and associated plants, with a revision of the genus.

The genus Bursaphelenchus includes B. xylophilus (Steiner et Buhrer, 1934) Nickle, 1981, which is of world economic and quarantine importance. Distinction among several species of the pinewood nematodes species complex (PWNSC) is often difficult. Besides standard morphology, morphometrics and molecular biology, new tools are welcome to better understand this group. The computerized (or e-) key of this genus, presented in this communication, includes 74 species (complete list of valid species of the world fauna) and 35 characters, that were used by the taxonomic experts of this group, in the original descriptions. Morphology of sex organs (male spicules and female vulval region) was digitized and classified to distinguish alternative types. Several qualitative characters with overlapping character states (expressions) were transformed into the morphometric indices with the discontinuous ranges (characters of ratios of the spicule dimensions). Characters and their states (expressions) were illustrated in detail and supplied by brief user-friendly comments. E-key was created in the BIKEY identification system (Dianov & Lobanov, 1996-2004). The system has built-algorithm ranging characters depending on their diagnostic values at each step of identification. Matrix of species and the character states (structural part of the e-key database) may be easily transformed using statistical packages into the dendrograms of general phenetic similarities (UPGMA, standard distance: mean character difference). It may be useful in the detailed analysis of taxonomy and evolution of the genus and in its splitting to the species groups based on morphology. The verification of the dendrogram using the information on the species links with insect vectors and their associated plants, provided an opportunity to recognize the five clusters (xylophilus, hunti, eremus sensu stricto, tusciae and piniperdae sensu stricto), which seem to be the natural species groups. The hypothesis about the origin and the first stages of the genus evolution is proposed. A general review of the genus Bursaphelenchus is presented.

Computerized key of the genus genus Laimaphelenchus Fuchs, 1937

The Order Aphelenchida contains several genera of economic importance, namely Aphelenchoides and Bursaphelenchus. Nematode species belonging to these 2 genera frequently co-habit with other genera such as Laimaphelenchus. It is therefore important to clearly distinguish them, as well as understand the group´s biodiversity. A computerized, or e-key, for the genus Laimaphelenchus Fuchs has been developed in the BiKey Identification system (Dianov & Lobanov, 1996-2004). The e-key includes 14 species and 34 characters (from 2 to 6 character states each). It also includes the built-in algorithm ranging characters according their diagnostic values to minimize the number of the diagnosis steps (average number of steps is 2.7; values are re-calculated at each step). The most important characters (as calculated by BiKey) are: length of posterior branch of the female genital system; excretory pore position; vulval anterior flap shape; number pairs of mail tale papillae; male bursa shape (ventral view); number of tail tip setae in female; female tail tip stub shape; presence of mucro on tail tip in male. Key is pictorial (image-operating), multientry, as other BiKey products.

IP/optical integration in access network infrastructures: key issues on resource provisioning

This thesis contributes to the advancement of Fiber-Wireless (FiWi) access technologies, through the development of algorithms for resource allocation and energy efficient routing. FiWi access networks use both optical and wireless/cellular technologies to provide high bandwidth and ubiquity, required by users and current high demanding services. FiWi access technologies are divided in two parts. In one of the parts, fiber is brought from the central office to near the users, while in the other part wireless routers or base stations take over and provide Internet access to users. Many technologies can be used at both the optical and wireless parts, which lead to different integration and optimization problems to be solved. In this thesis, the focus will be on FiWi access networks that use a passive optical network at the optical section and a wireless mesh network at the wireless section. In such networks, two important aspects that influence network performance are: allocation of resources and traffic routing throughout the mesh section. In this thesis, both problems are addressed. A fair bandwidth allocation algorithm is developed, which provides fairness in terms of bandwidth and in terms of experienced delays among all users. As for routing, an energy efficient routing algorithm is proposed that optimizes sleeping and productive periods throughout the wireless and optical sections. To develop the stated algorithms, game theory and networks formation theory were used. These are powerful mathematical tools that can be used to solve problems involving agents with conflicting interests. Since, usually, these tools are not common knowledge, a brief survey on game theory and network formation theory is provided to explain the concepts that are used throughout the thesis. As such, this thesis also serves as a showcase on the use of game theory and network formation theory to develop new algorithms.

Changing patterns of first injection across key periods of the French Harm Reduction Policy: PrimInject, a cross sectional analysis

Background: Monitoring of emerging modes of drug consumption in France has identified new patterns of injection among youths with diverse social backgrounds, which may explain the persistence of high rates of hepatitis C virus infection. The circumstances surrounding the first injection have been poorly documented in the group of heavy drug users and in the context of the French opioid substitution treatment (OST) policy that provides expanded access to high-dosage buprenorphine (BHD). Methods: An Internet survey (Priminject) was conducted from October 2010 to March 2011 with French drug users. Four time periods were compared based on critical dates throughout the implementation of the Harm Reduction Policy in France. Results: Compared with drug users who injected for the first time prior to 1995, the aspects of drug use for users who recently injected for the first time were as follows: (1) experimentation with miscellaneous drugs before the first injection; (2) an older age at the time of first injection; (3) heroin as the drug of choice for an individual’s first injection, notwithstanding the increased usage of stimulant drugs; (4) BHD did not appear to be a pathway to injection; and (5) an increased number of users who injected their first time alone, without the help or presence of another individual. Conclusion: The PrimInject study showed that there is a group of injection drug users that is larger than the group of injection drug users observed in previous studies; therefore, it is necessary to diversify programs to reach the entire spectrum of high-risk users.

Bird Key S200

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Bird Key S200 Recreational Shellfish Ground in Charleston County.