Compilation of somatic mutations of the CDKN2 gene in human cancers : non-random distribution of base substitutions

The CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, is a tumour suppressor gene that maps to chromosome band 9p21-p22. The most common mechanism of inactivation of this gene in human cancers is through homozygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKN2 have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length 156 amino acid form of p16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKN2 gene, and possible explanations for this are discussed.

CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein

The CDKN2A gene encodes p16 (CDKN2A), a cell-cycle inhibitor protein which prevents inappropriate cell cycling and, hence, proliferation. Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM). We therefore sequenced exons 1alpha and 2 of CDKN2A using lymphocyte DNA isolated from index cases from 67 families with cancers at multiple sites, where the patterns of cancer did not resemble those attributable to known genes such as hMLH1, hMLH2, BRCA1, BRCA2, TP53 or other cancer susceptibility genes. We found one mutation, a mis-sense mutation resulting in a methionine to isoleucine change at codon 53 (M531) of exon 2. The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM. Other family members had been diagnosed with oral cancer (2 persons), bladder cancer (1 person) and possibly gall-bladder cancer. While this mutation has been reported in Australian and North American melanoma kindreds, we did not observe it in 618 chromosomes from Scottish and Canadian controls. Functional studies revealed that the CDKN2A variant carrying the M531 change was unable to bind effectively to CDK4, showing that this mutation is of pathological significance. Our results have confirmed that CDKN2A mutations are not limited to FAMMM kindreds but also demonstrate that multi-site cancer families without melanoma are very unlikely to contain CDKN2A mutations.

Patterning of tailored polycarbonate based non-chemically amplified resists using extreme ultraviolet lithography

A series of high-performance polycarbonates have been prepared with glass-transition temperatures and decomposition temperatures that are tunable by varying the repeat-unit chemical structure. Patterning of the polymers with extreme UV lithography has been achieved by taking advantage of direct photoinduced chain scission of the polymer chains, which results in a molecular-weight based solubility switch. After selective development of the irradiated regions of the polymers, feature sizes as small as 28.6 nm have been printed and the importance of resist-developer interactions for maximizing image quality has been demonstrated.

Microwave curing of non-traditional polymer materials used in manufacture of injection moulds

Microwave heating technology is a cost-effective alternative way for heating and curing of used in polymer processing of various alternate materials. The work presented in this paper addresses the attempts made by the authors to study the glass transition temperature and curing of materials such as casting resins R2512, R2515 and laminating resin GPR 2516 in combination with two hardeners ADH 2403 and ADH 2409. The magnetron microwave generator used in this research is operating at a frequency of 2.45 GHz with a hollow rectangular waveguide. During this investigation it has been noted that microwave heated mould materials resulted with higher glass transition temperatures and better microstructure. It also noted that Microwave curing resulted in a shorter curing time to reach the maximum percentage cure. From this study it can be concluded that microwave technology can be efficiently and effectively used to cure new generation alternate polymer materials for manufacture of injection moulds in a rapid and efficient manner. Microwave curing resulted in a shorter curing time to reach the maximum percentage cure.

Reduction of functionalized graphite oxides by trioctylphosphine in non-polar organic solvents

Graphene, functionalized with oleylamine (OA) and soluble in non-polar organic solvents, was produced on a large scale with a high yield by combining the Hummers process for graphite oxidation, an amine-coupling process to make OA-functionalized graphite oxide (OA-GO), and a novel reduction process using trioctylphosphine (TOP). TOP acts as both a reducing agent and an aggregation-prevention surfactant in the reduction of OA-GO in 1,2-dichlorobenzene (DCB). The reduction of OA-GO is confirmed by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and Raman spectroscopy. The exfoliation of GO, OA GO, and OA-functionalized graphene (OA-G) is verified by atomic force microscopy. The conductivity of TOP-reduced OA G, which is deduced from the current–voltage characteristics of a vacuum-filtered thin film, shows that the reduction of functionalized GO by TOP is as effective as the reduction of GO by hydrazine.

Resisting contradictions : non-Indigenous pre-service teacher responses to critical Indigenous studies

The study examines non-Indigenous pre-service teacher responses to the authorisation of Indigenous knowledge perspectives in compulsory Indigenous studies with a primary focus on exploring the nature and effects of resistance. It draws on the philosophies of the Japanangka teaching and research paradigm (West, 2000), relationship theory (Graham, 1999), Indigenist methodologies and decolonisation approaches to examine this resistance. A Critical Indigenist Study was employed to investigate how non-Indigenous pre-service teachers managed their learning, and how they articulated shifts in resistance as they progressed through their studies. This study explains resistance to compulsory Indigenous and how it can be targeted by Indigenist Standpoint Pedagogy. The beginning transformations in pre-service teacher positioning in relation to Australian history, contemporary educational practice, and professional identity was also explored.

Accurately simulating the production of radiotherapy portal images using non-zero beam angles

In this study, the delivery and portal imaging of one square-field and one conformal radiotherapy treatment was simulated using the Monte Carlo codes BEAMnrc and DOSXYZnrc. The treatment fields were delivered to a humanoid phantom from different angles by a 6 MV photon beam linear accelerator, with an amorphous-silicon electronic portal imaging device (a-Si EPID) used to provide images of the phantom generated by each field. The virtual phantom preparation code CTCombine was used to combine a computed-tomography-derived model of the irradiated phantom with a simple, rectilinear model of the a-Si EPID, at each beam angle used in the treatment. Comparison of the resulting experimental and simulated a-Si EPID images showed good agreement, within \[gamma](3%, 3 mm), indicating that this method may be useful in providing accurate Monte Carlo predictions of clinical a-Si EPID images, for use in the verification of complex radiotherapy treatments.

Non-redundant sequential association rule mining based on closed sequential patterns

In many applications, e.g., bioinformatics, web access traces, system utilisation logs, etc., the data is naturally in the form of sequences. People have taken great interest in analysing the sequential data and finding the inherent characteristics or relationships within the data. Sequential association rule mining is one of the possible methods used to analyse this data. As conventional sequential association rule mining very often generates a huge number of association rules, of which many are redundant, it is desirable to find a solution to get rid of those unnecessary association rules. Because of the complexity and temporal ordered characteristics of sequential data, current research on sequential association rule mining is limited. Although several sequential association rule prediction models using either sequence constraints or temporal constraints have been proposed, none of them considered the redundancy problem in rule mining. The main contribution of this research is to propose a non-redundant association rule mining method based on closed frequent sequences and minimal sequential generators. We also give a definition for the non-redundant sequential rules, which are sequential rules with minimal antecedents but maximal consequents. A new algorithm called CSGM (closed sequential and generator mining) for generating closed sequences and minimal sequential generators is also introduced. A further experiment has been done to compare the performance of generating non-redundant sequential rules and full sequential rules, meanwhile, performance evaluation of our CSGM and other closed sequential pattern mining or generator mining algorithms has also been conducted. We also use generated non-redundant sequential rules for query expansion in order to improve recommendations for infrequently purchased products.

Supplement : Efficient weak second-order stochastic Runge-Kutta methods for non-commutative Stratonvich stochastic differential equations

This paper gives a modification of a class of stochastic Runge–Kutta methods proposed in a paper by Komori (2007). The slight modification can reduce the computational costs of the methods significantly.