Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

A lightweight biometric signature scheme for user authentication over networks

We introduce a lightweight biometric solution for user authentication over networks using online handwritten signatures. The algorithm proposed is based on a modified Hausdorff distance and has favorable characteristics such as low computational cost and minimal training requirements. Furthermore, we investigate an information theoretic model for capacity and performance analysis for biometric authentication which brings additional theoretical insights to the problem. A fully functional proof-of-concept prototype that relies on commonly available off-the-shelf hardware is developed as a client-server system that supports Web services. Initial experimental results show that the algorithm performs well despite its low computational requirements and is resilient against over-the-shoulder attacks.

Iris based identity verification robust to sample presentation security attacks

Iris based identity verification is highly reliable but it can also be subject to attacks. Pupil dilation or constriction stimulated by the application of drugs are examples of sample presentation security attacks which can lead to higher false rejection rates. Suspects on a watch list can potentially circumvent the iris based system using such methods. This paper investigates a new approach using multiple parts of the iris (instances) and multiple iris samples in a sequential decision fusion framework that can yield robust performance. Results are presented and compared with the standard full iris based approach for a number of iris degradations. An advantage of the proposed fusion scheme is that the trade-off between detection errors can be controlled by setting parameters such as the number of instances and the number of samples used in the system. The system can then be operated to match security threat levels. It is shown that for optimal values of these parameters, the fused system also has a lower total error rate.

Feature-domain super-resolution for iris recognition

Uncooperative iris identification systems at a distance suffer from poor resolution of the acquired iris images, which significantly degrades iris recognition performance. Super-resolution techniques have been employed to enhance the resolution of iris images and improve the recognition performance. However, most existing super-resolution approaches proposed for the iris biometric super-resolve pixel intensity values, rather than the actual features used for recognition. This paper thoroughly investigates transferring super-resolution of iris images from the intensity domain to the feature domain. By directly super-resolving only the features essential for recognition, and by incorporating domain specific information from iris models, improved recognition performance compared to pixel domain super-resolution can be achieved. A framework for applying super-resolution to nonlinear features in the feature-domain is proposed. Based on this framework, a novel feature-domain super-resolution approach for the iris biometric employing 2D Gabor phase-quadrant features is proposed. The approach is shown to outperform its pixel domain counterpart, as well as other feature domain super-resolution approaches and fusion techniques.

An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn’s Disease cohort

BACKGROUND AND AIMS: Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. METHODS: We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. RESULTS: A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95 % CI P = 1 × 10(-4)) which was higher than any factor considered independently. CONCLUSIONS: The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.

Human identification at a distance using iris and face

This research has successfully applied super-resolution and multiple modality fusion techniques to address the major challenges of human identification at a distance using face and iris. The outcome of the research is useful for security applications.

Understanding the signature pedagogy of the design studio and the opportunities for its technological enhancement

This paper presents an analysis of the studio as the signature pedagogy of design education. A number of theoretical models of learning, pedagogy, and education are used to interrogate the studio for its advantages and shortcomings, and to identify opportunities for the integration of new technologies and to explore the affordances that they might offer. In particular the theoretical ideas of signature pedagogies, conversational frameworks, and pedagogical patterns are used to justify the ‘unique’ status of the studio as a dominant learning environment and mode of delivery within design education. Such analysis identifies the opportunities for technological intervention and enhancement of the design studio through a re-examining of its fundamental pedagogical signature. This paper maps the dimensions and qualities that define the signature pedagogy against a range of delivery modes and technological media forms. Through such investigation it seeks to identify appropriate opportunities for technology; in essence offering a structure or framework for the analysis of future enquiry and experimentation.

Adapting Lyubashevsky's signature schemes to the ring signature setting

Basing signature schemes on strong lattice problems has been a long standing open issue. Today, two families of lattice-based signature schemes are known: the ones based on the hash-and-sign construction of Gentry et al.; and Lyubashevsky’s schemes, which are based on the Fiat-Shamir framework. In this paper we show for the first time how to adapt the schemes of Lyubashevsky to the ring signature setting. In particular we transform the scheme of ASIACRYPT 2009 into a ring signature scheme that provides strong properties of security under the random oracle model. Anonymity is ensured in the sense that signatures of different users are within negligible statistical distance even under full key exposure. In fact, the scheme satisfies a notion which is stronger than the classical full key exposure setting as even if the keypair of the signing user is adversarially chosen, the statistical distance between signatures of different users remains negligible. Considering unforgeability, the best lattice-based ring signature schemes provide either unforgeability against arbitrary chosen subring attacks or insider corruption in log-sized rings. In this paper we present two variants of our scheme. In the basic one, unforgeability is ensured in those two settings. Increasing signature and key sizes by a factor k (typically 80 − 100), we provide a variant in which unforgeability is ensured against insider corruption attacks for arbitrary rings. The technique used is pretty general and can be adapted to other existing schemes.

A security system based on human iris identification using wavelet transform

A security system based on the recognition of the iris of human eyes using the wavelet transform is presented. The zero-crossings of the wavelet transform are used to extract the unique features obtained from the grey-level profiles of the iris. The recognition process is performed in two stages. The first stage consists of building a one-dimensional representation of the grey-level profiles of the iris, followed by obtaining the wavelet transform zerocrossings of the resulting representation. The second stage is the matching procedure for iris recognition. The proposed approach uses only a few selected intermediate resolution levels for matching, thus making it computationally efficient as well as less sensitive to noise and quantisation errors. A normalisation process is implemented to compensate for size variations due to the possible changes in the camera-to-face distance. The technique has been tested on real images in both noise-free and noisy conditions. The technique is being investigated for real-time implementation, as a stand-alone system, for access control to high-security areas.

Decision fusion from parts and samples for robust iris recognition

Fusion techniques can be used in biometrics to achieve higher accuracy. When biometric systems are in operation and the threat level changes, controlling the trade-off between detection error rates can reduce the impact of an attack. In a fused system, varying a single threshold does not allow this to be achieved, but systematic adjustment of a set of parameters does. In this paper, fused decisions from a multi-part, multi-sample sequential architecture are investigated for that purpose in an iris recognition system. A specific implementation of the multi-part architecture is proposed and the effect of the number of parts and samples in the resultant detection error rate is analysed. The effectiveness of the proposed architecture is then evaluated under two specific cases of obfuscation attack: miosis and mydriasis. Results show that robustness to such obfuscation attacks is achieved, since lower error rates than in the case of the non-fused base system are obtained.

Short signature without random oracles and the SDH assumption in bilinear groups

We describe a short signature scheme that is strongly existentially unforgeable under an adaptive chosen message attack in the standard security model. Our construction works in groups equipped with an efficient bilinear map, or, more generally, an algorithm for the Decision Diffie-Hellman problem. The security of our scheme depends on a new intractability assumption we call Strong Diffie-Hellman (SDH), by analogy to the Strong RSA assumption with which it shares many properties. Signature generation in our system is fast and the resulting signatures are as short as DSA signatures for comparable security. We give a tight reduction proving that our scheme is secure in any group in which the SDH assumption holds, without relying on the random oracle model.

Multiple-time signature schemes against adaptive chosen message attacks

Multiple-time signatures are digital signature schemes where the signer is able to sign a predetermined number of messages. They are interesting cryptographic primitives because they allow to solve many important cryptographic problems, and at the same time offer substantial efficiency advantage over ordinary digital signature schemes like RSA. Multiple-time signature schemes have found numerous applications, in ordinary, on-line/off-line, forward-secure signatures, and multicast/stream authentication. We propose a multiple-time signature scheme with very efficient signing and verifying. Our construction is based on a combination of one-way functions and cover-free families, and it is secure against the adaptive chosen-message attack.

Determining epithelial contribution to in vivo mesenchymal tumour expression signature using species-specific microarray profiling analysis of xenografts

Gene expression profiling using microarrays and xenograft transplants of human cancer cell lines are both popular tools to investigate human cancer. However, the undefined degree of cross hybridization between the mouse and human genomes hinders the use of microarrays to characterize gene expression of both the host and the cancer cell within the xenograft. Since an increasingly recognized aspect of cancer is the host response (or cancer-stroma interaction), we describe here a bioinformatic manipulation of the Affymetrix profiling that allows interrogation of the gene expression of both the mouse host and the human tumour. Evidence of microenvironmental regulation of epithelial mesenchymal transition of the tumour component in vivo is resolved against a background of mesenchymal gene expression. This tool could allow deeper insight to the mechanism of action of anti-cancer drugs, as typically novel drug efficacy is being tested in xenograft systems.