In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

Informal interactions between audit committees and internal audit functions : exploratory evidence and directions for future research

Purpose – This paper aims to recognise the importance of informal processes within corporate governance and complement existing research in this area by investigating factors associated with the existence of informal interactions between audit committees and internal audit functions and in providing directions for future research. Design/methodology/approach – To examine the existence and drivers of informal interactions between audit committees and internal audit functions, this paper relies on a questionnaire survey of chief audit executives (CAEs) in the UK from listed and non-listed, as well as financial and non-financial, companies. While prior qualitative research suggests that informal interactions do take place, most of the evidence is based on particular organisational setting or on a very small range of interviews. The use of a questionnaire enabled the examination of the existence of internal interactions across a relatively larger number of entities. Findings – The paper finds evidence of audit committees and internal audit functions engaging in informal interactions in addition to formal pre-scheduled regular meetings. Informal interactions complement formal meetings with the audit committee and as such represent additional opportunities for the audit committees to monitor internal audit functions. Audit committees’ informal interactions are significantly and positively associated with audit committee independence, audit chair’s knowledge and experience, and internal audit quality. Originality/value – The results demonstrate the importance of the background of the audit committee chair for the effectiveness of the governance process. This is possibly the first paper to examine the relationship between audit committee quality and internal audit, on the existence and driver of informal interactions. Policy makers should recognize that in addition to formal mechanisms, informal processes, such as communication outside of formal pre-scheduled meetings, play a significant role in corporate governance.

Bat colony size reduction coincides with clear-fell harvest operations and high rates of roost loss in plantation forest

Clear-fell harvest of forest concerns many wildlife biologists because of loss of vital resources such as roosts or nests, and effects on population viability. However, actual impact has not been quantified. Using New Zealand long-tailed bats (Chalinolobus tuberculatus) as a model species we investigated impacts of clear-fell logging on bats in plantation forest. C. tuberculatus roost within the oldest stands in plantation forest so it was likely roost availability would decrease as harvest operations occurred. We predicted that post-harvest: (1) roosting range sizes would be smaller, (2) fewer roosts would be used, and (3) colony size would be smaller. We captured and radiotracked C. tuberculatus to day-roosts in Kinleith Forest, an exotic plantation forest, over three southern hemisphere summers (Season 1 October 2006–March 2007; Season 2 November 2007–March 2008; and Season 3 November 2008–March 2009). Individual roosting ranges (100% MCPs) post harvest were smaller than those in areas that had not been harvested, and declined in area during the 3 years. Following harvest, bats used fewer roosts than those in areas that had not been harvested. Over 3 years 20.7% of known roosts were lost: 14.5% due to forestry operations and 6.2% due to natural tree fall. Median colony size was 4.0 bats (IQR = 2.0–8.0) and declined during the study, probably because of locally high levels of roost loss. Post harvest colonies were smaller than colonies in areas that had not been harvested. Together, these results suggest the impact of clear-fell harvest on long-tailed bat populations is negative.

Building indifferentiable compression functions from the PGV compression functions

Preneel, Govaerts and Vandewalle (PGV) analysed the security of single-block-length block cipher based compression functions assuming that the underlying block cipher has no weaknesses. They showed that 12 out of 64 possible compression functions are collision and (second) preimage resistant. Black, Rogaway and Shrimpton formally proved this result in the ideal cipher model. However, in the indifferentiability security framework introduced by Maurer, Renner and Holenstein, all these 12 schemes are easily differentiable from a fixed input-length random oracle (FIL-RO) even when their underlying block cipher is ideal. We address the problem of building indifferentiable compression functions from the PGV compression functions. We consider a general form of 64 PGV compression functions and replace the linear feed-forward operation in this generic PGV compression function with an ideal block cipher independent of the one used in the generic PGV construction. This modified construction is called a generic modified PGV (MPGV). We analyse indifferentiability of the generic MPGV construction in the ideal cipher model and show that 12 out of 64 MPGV compression functions in this framework are indifferentiable from a FIL-RO. To our knowledge, this is the first result showing that two independent block ciphers are sufficient to design indifferentiable single-block-length compression functions.

Structural damage detection method using frequency response functions

Structural damage detection using measured dynamic data for pattern recognition is a promising approach. These pattern recognition techniques utilize artificial neural networks and genetic algorithm to match pattern features. In this study, an artificial neural network–based damage detection method using frequency response functions is presented, which can effectively detect nonlinear damages for a given level of excitation. The main objective of this article is to present a feasible method for structural vibration–based health monitoring, which reduces the dimension of the initial frequency response function data and transforms it into new damage indices and employs artificial neural network method for detecting different levels of nonlinearity using recognized damage patterns from the proposed algorithm. Experimental data of the three-story bookshelf structure at Los Alamos National Laboratory are used to validate the proposed method. Results showed that the levels of nonlinear damages can be identified precisely by the developed artificial neural networks. Moreover, it is identified that artificial neural networks trained with summation frequency response functions give higher precise damage detection results compared to the accuracy of artificial neural networks trained with individual frequency response functions. The proposed method is therefore a promising tool for structural assessment in a real structure because it shows reliable results with experimental data for nonlinear damage detection which renders the frequency response function–based method convenient for structural health monitoring.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

Cryptographic hash functions

Cryptographic hash functions are an important tool of cryptography and play a fundamental role in efficient and secure information processing. A hash function processes an arbitrary finite length input message to a fixed length output referred to as the hash value. As a security requirement, a hash value should not serve as an image for two distinct input messages and it should be difficult to find the input message from a given hash value. Secure hash functions serve data integrity, non-repudiation and authenticity of the source in conjunction with the digital signature schemes. Keyed hash functions, also called message authentication codes (MACs) serve data integrity and data origin authentication in the secret key setting. The building blocks of hash functions can be designed using block ciphers, modular arithmetic or from scratch. The design principles of the popular Merkle–Damgård construction are followed in almost all widely used standard hash functions such as MD5 and SHA-1.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

On hash functions using checksums

We analyse the security of iterated hash functions that compute an input dependent checksum which is processed as part of the hash computation. We show that a large class of such schemes, including those using non-linear or even one-way checksum functions, is not secure against the second preimage attack of Kelsey and Schneier, the herding attack of Kelsey and Kohno and the multicollision attack of Joux. Our attacks also apply to a large class of cascaded hash functions. Our second preimage attacks on the cascaded hash functions improve the results of Joux presented at Crypto’04. We also apply our attacks to the MD2 and GOST hash functions. Our second preimage attacks on the MD2 and GOST hash functions improve the previous best known short-cut second preimage attacks on these hash functions by factors of at least 226 and 254, respectively. Our herding and multicollision attacks on the hash functions based on generic checksum functions (e.g., one-way) are a special case of the attacks on the cascaded iterated hash functions previously analysed by Dunkelman and Preneel and are not better than their attacks. On hash functions with easily invertible checksums, our multicollision and herding attacks (if the hash value is short as in MD2) are more efficient than those of Dunkelman and Preneel.

On the Collision and Preimage Resistance of Certain Two-Call Hash Functions

In this paper we present concrete collision and preimage attacks on a large class of compression function constructions making two calls to the underlying ideal primitives. The complexity of the collision attack is above the theoretical lower bound for constructions of this type, but below the birthday complexity; the complexity of the preimage attack, however, is equal to the theoretical lower bound. We also present undesirable properties of some of Stam’s compression functions proposed at CRYPTO ’08. We show that when one of the n-bit to n-bit components of the proposed 2n-bit to n-bit compression function is replaced by a fixed-key cipher in the Davies-Meyer mode, the complexity of finding a preimage would be 2 n/3. We also show that the complexity of finding a collision in a variant of the 3n-bits to 2n-bits scheme with its output truncated to 3n/2 bits is 2 n/2. The complexity of our preimage attack on this hash function is about 2 n . Finally, we present a collision attack on a variant of the proposed m + s-bit to s-bit scheme, truncated to s − 1 bits, with a complexity of O(1). However, none of our results compromise Stam’s security claims.

On Randomizing Hash Functions to Strengthen the Security of Digital Signatures

Halevi and Krawczyk proposed a message randomization algorithm called RMX as a front-end tool to the hash-then-sign digital signature schemes such as DSS and RSA in order to free their reliance on the collision resistance property of the hash functions. They have shown that to forge a RMX-hash-then-sign signature scheme, one has to solve a cryptanalytical task which is related to finding second preimages for the hash function. In this article, we will show how to use Dean’s method of finding expandable messages for finding a second preimage in the Merkle-Damgård hash function to existentially forge a signature scheme based on a t-bit RMX-hash function which uses the Davies-Meyer compression functions (e.g., MD4, MD5, SHA family) in 2 t/2 chosen messages plus 2 t/2 + 1 off-line operations of the compression function and similar amount of memory. This forgery attack also works on the signature schemes that use Davies-Meyer schemes and a variant of RMX published by NIST in its Draft Special Publication (SP) 800-106. We discuss some important applications of our attack.

Cryptographic Hash Functions

In the modern era of information and communication technology, cryptographic hash functions play an important role in ensuring the authenticity, integrity, and nonrepudiation goals of information security as well as efficient information processing. This entry provides an overview of the role of hash functions in information security, popular hash function designs, some important analytical results, and recent advances in this field.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.