Chain scission resists for extreme ultraviolet lithography based on high performance polysulfone-containing polymers

A series of polymers with a comb architecture were prepared where the poly(olefin sulfone) backbone was designed to be highly sensitive to extreme ultraviolet (EUV) radiation, while the well-defined poly(methyl methacrylate) (PMMA) arms were incorporated with the aim of increasing structural stability. It is hypothesized that upon EUV radiation rapid degradation of the polysulfone backbone will occur leaving behind the well-defined PMMA arms. The synthesized polymers were characterised and have had their performance as chain-scission EUV photoresists evaluated. It was found that all materials possess high sensitivity towards degradation by EUV radiation (E0 in the range 4–6 mJ cm−2). Selective degradation of the poly(1-pentene sulfone) backbone relative to the PMMA arms was demonstrated by mass spectrometry headspace analysis during EUV irradiation and by grazing-angle ATR-FTIR. EUV interference patterning has shown that materials are capable of resolving 30 nm 1:1 line:space features. The incorporation of PMMA was found to increase the structural integrity of the patterned features. Thus, it has been shown that terpolymer materials possessing a highly sensitive poly(olefin sulfone) backbone and PMMA arms are able to provide a tuneable materials platform for chain scission EUV resists. These materials have the potential to benefit applications that require nanopattering, such as computer chip manufacture and nano-MEMS.

An FPGA-based approach to multi-objective evolutionary algorithm for multi-disciplinary design optimisation

This paper investigates the field programmable gate array (FPGA) approach for multi-objective and multi-disciplinary design optimisation (MDO) problems. One class of optimisation method that has been well-studied and established for large and complex problems, such as those inherited in MDO, is multi-objective evolutionary algorithms (MOEAs). The MOEA, nondominated sorting genetic algorithm II (NSGA-II), is hardware implemented on an FPGA chip. The NSGA-II on FPGA application to multi-objective test problem suites has verified the designed implementation effectiveness. Results show that NSGA-II on FPGA is three orders of magnitude better than the PC based counterpart.

FPGA implementation of an evolutionary algorithm for autonomous unmanned aerial vehicle on-board path planning

In this paper, a hardware-based path planning architecture for unmanned aerial vehicle (UAV) adaptation is proposed. The architecture aims to provide UAVs with higher autonomy using an application specific evolutionary algorithm (EA) implemented entirely on a field programmable gate array (FPGA) chip. The physical attributes of an FPGA chip, being compact in size and low in power consumption, compliments it to be an ideal platform for UAV applications. The design, which is implemented entirely in hardware, consists of EA modules, population storage resources, and three-dimensional terrain information necessary to the path planning process, subject to constraints accounted for separately via UAV, environment and mission profiles. The architecture has been successfully synthesised for a target Xilinx Virtex-4 FPGA platform with 32% logic slices utilisation. Results obtained from case studies for a small UAV helicopter with environment derived from LIDAR (Light Detection and Ranging) data verify the effectiveness of the proposed FPGA-based path planner, and demonstrate convergence at rates above the typical 10 Hz update frequency of an autopilot system.

Books, toys and tablets : playing and learning in the age of digital media

Introduction During a recent study of how parents source information about children‘s early learning, one of us made our first serious foray into a local store licensed to the global chain Toys'R' Us. While walking the aisles, closely observing layout, signage and stock, several things became obvious. Firstly, large numbers of toys were labeled'educational'. Secondly, many toys in that category were intended for children under the age of two years. These were further differentiated as intended for 'babies' or 'infants', and sub-categorized on packaging or shelving using even smaller age increments (e.g. 0-3 months, 12-18 months, and so on). Thirdly, many products were labeled as 'interactive' and 'learning' toys that promised to assist children‘s early learning and development. The activation of some of these toys relied on embedded computer chip technology and promised to 'connect' children with the home television, computer and the Internet. These products were hybrids between a toy and a platform for digital media interaction. Closer inspection of toy packaging and other promotional material suggested that industry had begun to invest heavily in developing highly differentiated children‘s markets for products that yoked together concepts of learning and development, the 'fun toy' that incorporates digital technology, and offline- and online participation. In this chapter we explore the growth of this contemporary cultural phenomenon that now connects books, toys and mobile digital media with children‘s play and learning.

High court determines that it cannot be assumed that hot chips are only eaten at lunch

In Strong v Woolworth Ltd (t/as Big W) (2012) 285 ALR 420 the appellant was injured when she fell at a shopping centre outside the respondent’s premises. The appellant was disabled, having had her right leg amputated above the knee and therefore walked with crutches. One of the crutches came into contact with a hot potato chip which was on the floor, causing the crutch to slip and the appellant to fall. The appellant sued in negligence, alleging that the respondent was in breach of its duty of care by failing to institute and maintain a cleaning system to detect spillages and foreign objects within its sidewalk sales area. The issue before the High Court was whether it could be established on the balance of probabilities as to when the hot chip had fallen onto the ground so as to prove causation in fact...

Experiences with implementing common mathematical operations using field programmable gate arrays

Many computationally intensive scientific applications involve repetitive floating point operations other than addition and multiplication which may present a significant performance bottleneck due to the relatively large latency or low throughput involved in executing such arithmetic primitives on commod- ity processors. A promising alternative is to execute such primitives on Field Programmable Gate Array (FPGA) hardware acting as an application-specific custom co-processor in a high performance reconfig- urable computing platform. The use of FPGAs can provide advantages such as fine-grain parallelism but issues relating to code development in a hardware description language and efficient data transfer to and from the FPGA chip can present significant application development challenges. In this paper, we discuss our practical experiences in developing a selection of floating point hardware designs to be implemented using FPGAs. Our designs include some basic mathemati cal library functions which can be implemented for user defined precisions suitable for novel applications requiring non-standard floating point represen- tation. We discuss the details of our designs along with results from performance and accuracy analysis tests.

Upper-body morbidity after breast cancer : incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care

The purpose of this paper is to review the incidence of upper-body morbidity (arm and breast symptoms, impairments, and lymphedema), methods for diagnosis, and prevention and treatment strategies. It was also the purpose to highlight the evidence base for integration of prospective surveillance for upper-body morbidity within standard clinical care of women with breast cancer. Between 10% and 64% of women report upper-body symptoms between 6 months and 3 years after breast cancer, and approximately 20% develop lymphedema. Symptoms remain common into longer-term survivorship, and although lymphedema may be transient for some, those who present with mild lymphedema are at increased risk of developing moderate to severe lymphedema. The etiology of morbidity seems to be multifactorial, with the most consistent risk factors being those associated with extent of treatment. However, known risk factors cannot reliably distinguish between those who will and will not develop upper-body morbidity. Upper-body morbidity may be treatable with physical therapy. There is also evidence in support of integrating regular surveillance for upper-body morbidity into the routine care provided to women with breast cancer, with early diagnosis potentially contributing to more effective management and prevention of progression of these conditions.

Monte Carlo-based diode design for correction-less small field dosimetry

Due to their small collecting volume diodes are commonly used in small field dosimetry. However the relative sensitivity of a diode increases with decreasing small field size. Conversely, small air gaps have been shown to cause a significant decrease in the sensitivity of a detector as the field size is decreased. Therefore this study uses Monte Carlo simulations to look at introducing air upstream to diodes such that they measure with a constant sensitivity across all field sizes in small field dosimetry. Varying thicknesses of air were introduced onto the upstream end of two commercial diodes (PTW 60016 photon diode and PTW 60017 electron diode), as well as a theoretical unenclosed silicon chip using field sizes as small as 5 mm × 5 mm . The metric D_(w,Q)/D_(Det,Q) used in this study represents the ratio of the dose to a point of water to the dose to the diode active volume, for a particular field size and location. The optimal thickness of air required to provide a constant sensitivity across all small field sizes was found by plotting D_(w,Q)/D_(Det,Q) as a function of introduced air gap size for various field sizes, and finding the intersection point of these plots. That is, the point at which D_(w,Q)/D_(Det,Q) was constant for all field sizes was found. The optimal thickness of air was calculated to be 3.3 mm, 1.15 mm and 0.10 mm for the photon diode, electron diode and unenclosed silicon chip respectively. The variation in these results was due to the different design of each detector. When calculated with the new diode design incorporating the upstream air gap, k_(Q_clin 〖,Q〗_msr)^(f_clin 〖,f〗_msr ) was equal to unity to within statistical uncertainty (0.5 %) for all three diodes. Cross-axis profile measurements were also improved with the new detector design. The upstream air gap could be implanted on the commercial diodes via a cap consisting of the air cavity surrounded by water equivalent material. The results for the unclosed silicon chip show that an ideal small field dosimetry diode could be created by using a silicon chip with a small amount of air above it.

Saliva-derived DNA performs well in large-scale, high-density single-nucleotide polymorphism microarray studies

As of June 2009, 361 genome-wide association studies (GWAS) had been referenced by the HuGE database. GWAS require DNA from many thousands of individuals, relying on suitable DNA collections. We recently performed a multiple sclerosis (MS) GWAS where a substantial component of the cases (24%) had DNA derived from saliva. Genotyping was done on the Illumina genotyping platform using the Infinium Hap370CNV DUO microarray. Additionally, we genotyped 10 individuals in duplicate using both saliva- and blood-derived DNA. The performance of blood- versus saliva-derived DNA was compared using genotyping call rate, which reflects both the quantity and quality of genotyping per sample and the “GCScore,” an Illumina genotyping quality score, which is a measure of DNA quality. We also compared genotype calls and GCScores for the 10 sample pairs. Call rates were assessed for each sample individually. For the GWAS samples, we compared data according to source of DNA and center of origin. We observed high concordance in genotyping quality and quantity between the paired samples and minimal loss of quality and quantity of DNA in the saliva samples in the large GWAS sample, with the blood samples showing greater variation between centers of origin. This large data set highlights the usefulness of saliva DNA for genotyping, especially in high-density single-nucleotide polymorphism microarray studies such as GWAS.

Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene

High density SNP arrays can be used to identify DNA copy number changes in tumors such as homozygous deletions of tumor suppressor genes and focal amplifications of oncogenes. Illumina Human CNV370 Bead chip arrays were used to assess the genome for unbalanced chromosomal events occurring in 39 cell lines derived from stage III metastatic melanomas. A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39). In addition, a number of focal homozygous deletions potentially targeting novel melanoma tumor suppressor genes were identified. Because of their likely functional significance for melanoma progression, FAS, CH25H, BMPR1A, ACTA2, and TFG were investigated in a larger cohort of melanomas through sequencing. Nonsynonymous mutations were identified in BMPR1A (1 of 43), ACTA2 (3 of 43), and TFG (5 of 103). A number of potentially important mutation events occurred in TFG including the identification of a mini mutation ‘‘hotspot’’ at amino acid residue 380 (P380S and P380L) and the presence of multiple mutations in two melanomas. Mutations in TFG may have important clinical relevance for current therapeutic strategies to treat metastatic melanoma.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

EUELC project : a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular - pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARβ genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes. Copyright©ERS Journals Ltd 2009.

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients

Recent studies suggest that genetic and environmental factors do not account for all the schizophrenia risk and epigenetics also plays a role in disease susceptibility. DNA methylation is a heritable epigenetic modification that can regulate gene expression. Genome-Wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium Human Methylation450 Bead Chip. After adjusting for age and post-mortem interval (PMI), 4 641 probes corresponding to 2 929 unique genes were found to be differentially methylated. Of those genes, 1 291 were located in a CpG island and 817 were in a promoter region. These include NOS1, AKT1, DTNBP1, DNMT1, PPP3CC and SOX10 which have previously been associated with schizophrenia. More than 100 of these genes overlap with a previous DNA methylation study of peripheral blood from schizophrenia patients in which 27 000 CpG sites were analysed. Unsupervised clustering analysis of the top 3 000 most variable probes revealed two distinct groups with significantly more people with schizophrenia in cluster one compared to controls (p = 1.74x10-4). The first cluster was composed of 88% of patients with schizophrenia and only 12% controls while the second cluster was composed of 27% of patients with schizophrenia and 73% controls. These results strongly suggest that differential DNA methylation is important in schizophrenia etiology and add support for the use of DNA methylation profiles as a future prognostic indicator of schizophrenia.

Response variation of optically stimulated luminescence dosimeters

This study investigates the variability in response of optically stimulated luminescence dosimeters (OSLDs). Examining the source of sensitivity variations in these dosimeters allows for a more comprehensive understanding of the Landauer nanoDots and their potential for current and future applications. In this work, OSLDs were scanned with a MicroCT scanner to determine potential sources for the variation in relative sensitivity across a selection of Landauer nanoDot dosimeters. Specifically, the correlation between a dosimeters relative sensitivity and the loading density of Al2O3:C powder was determined. When extrapolating the sensitive volume's radiodensity from the CT data, it was shown that there is a non-uniform distribution in crystal growth. It was calculated that a 0.05% change in the nominal volume of the chip produces a 1% change in the overall response. Additionally, the ‘true’ volume of an OSLD's sensitive material is, on average, 18% less than that which has been reported in literature, mainly due to the presence of air cavities in the material's structure. This work demonstrated that the amount of sensitive material is approximately linked to the total correction factor.

Direct lipid profiling of single cells from inkjet printed microarrays

The on-demand printing of living cells using inkjet technologies has recently been demonstrated and allows for the controlled deposition of cells in microarrays. Here, we show that such arrays can be interrogated directly by robot-controlled liquid microextraction coupled with chip-based nanoelectospray mass spectrometry. Such automated analyses generate a profile of abundant membrane lipids that are characteristic of cell type. Significantly, the spatial control in both deposition and extraction steps combined with the sensitivity of the mass spectrometric detection allows for robust molecular profiling of individual cells. © 2012 American Chemical Society.