Single nucleotide polymorphisms in clinics: Fantasy or reality for cancer?

Single nucleotide polymorphisms (SNPs) have been classically used for dissecting various human complex disorders using candidate gene studies. During the last decade, large scale SNP analysis i.e. genome-wide association studies (GWAS) have provided an agnostic approach to identify possible genetic loci associated with heterogeneous disease such as cancer susceptibility, prognosis of survival or drug response. Further, the advent of new technologies, including microarray based genotyping as well as high throughput next generation sequencing has opened new avenues for SNPs to be used in clinical practice. It is speculated that the utility of SNPs to understand the mechanisms, biology of variable drug response and ultimately treatment individualization based on the individual’s genome composition will be indispensable in the near future. In the current review, we discuss the advantages and disadvantages of the clinical utility of genetic variants in disease risk-prediction, prognosis, clinical outcome and pharmacogenomics. The lessons and challenges for the utility of SNP based biomarkers are also discussed, including the need for additional functional validation studies.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed as CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate tumor cells were mixed with mouse blood cells and the labelfree isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Characteristics of road factors in multi and single vehicle motorcycle crashes in Queensland

Motorcyclists were involved in 6.4% of all police-reported crashes and 12.5% of all fatal crashes in Queensland during 2004-2011. Of these crashes, 43% were single-vehicle (SV) and 57% were multi-vehicle (MV). The overall reduction in motorcycle crashes in this period masked different trends: single-vehicle crashes increased while MV motorcycle crashes decreased. However, little research has been undertaken to understand the similarities and differences between SV and MV motorcycle crashes in Queensland and the factors underlying these diverging trends. The descriptive analyses and regression model developed here confirm international research findings regarding the greater role of road infrastructure factors in SV crashes. In particular, road geometric factors such as horizontal and vertical alignment and road surface factors such as sealed/unsealed and wet/dry were more important in SV than MV crashes.

Single 2×1 domain orientation on Si(001) surfaces using aperiodic Bi line arrays

Studies of Bi heteroepitaxy on Si(001) have shown that lines grow to lengths of up to 500nm if the substrate is heated to above the Bi desorption temperature (500°C) during or after Bi deposition. Unlike many other nanoline systems, the lines formed by this nonequilibrium growth process have no detectable width dispersion. Although much attention has been given to the atomic geometery of the line, in this paper, we focus on how the lines can be used to create a majority 2×1 domain orientation. It is demonstrated that the Bi lines can be used to produce a single-domain orientation on Si(001) if the lines are grown on Si(001) surfaces with a regular distribution of single height steps. This is a compelling example of how a nanoscale motif can be used to modify mesoscopic surface structure on Si(001).

Prediction of a large-gap quantum-spin-Hall insulator: Diamond-like GaBi bilayer

A quantum-spin-Hall (QSH) state was achieved experimentally, albeit at a low critical temperature because of the narrow band gap of the bulk material. Twodimensional topological insulators are critically important for realizing novel topological applications. Using density functional theory (DFT), we demonstrated that hydrogenated GaBi bilayers (HGaBi) form a stable topological insulator with a large nontrivial band gap of 0.320 eV, based on the state-of-the-art hybrid functional method, which is implementable for achieving QSH states at room temperature. The nontrivial topological property of the HGaBi lattice can also be confirmed from the appearance of gapless edge states in the nanoribbon structure. Our results provide a versatile platform for hosting nontrivial topological states usable for important nanoelectronic device applications.

A robust approach to design a single facility layout plan in dynamic manufacturing environments using a permutation-based genetic algorithm

During the past few decades, developing efficient methods to solve dynamic facility layout problems has been focused on significantly by practitioners and researchers. More specifically meta-heuristic algorithms, especially genetic algorithm, have been proven to be increasingly helpful to generate sub-optimal solutions for large-scale dynamic facility layout problems. Nevertheless, the uncertainty of the manufacturing factors in addition to the scale of the layout problem calls for a mixed genetic algorithm–robust approach that could provide a single unlimited layout design. The present research aims to devise a customized permutation-based robust genetic algorithm in dynamic manufacturing environments that is expected to be generating a unique robust layout for all the manufacturing periods. The numerical outcomes of the proposed robust genetic algorithm indicate significant cost improvements compared to the conventional genetic algorithm methods and a selective number of other heuristic and meta-heuristic techniques.

ESR measurements of the partitioning of some new spin probes in n-octanol-water

The stable free radical 1,1,3,3-tetramethylisoindolin-2-yloxyl (TMIO) has proved to be very suitable for use as a spin probe for a number of applications. Because it is soluble mainly in non-polar liquids, there is a need for new derivatives that can be used in a variety of environments. This has been done by introducing substituents in the 5-position of the aromatic ring, namely carboxyl (CTMIO), trimethylamino (TMTMIOI) and sodium sulphonate (NaTMIOS). An accurate ESR method was developed for the measurement of partition coefficients in n-octanol–water. For comparison purposes the method was also applied to some Tempo derivatives. The effect of temperature on the rotational correlation times and the nitrogen-14 hyperfine coupling constant of some of the spin probes was investigated. There is evidence for dimerization of CTMIO to form a biradical

Spin it to win it: A comparison of constraints-led versus traditional coaching approaches

This thesis aimed to compare the effects of constraints-led and traditional coaching approaches on young cricket spin bowlers, with a specific research focus on increasing spin rates (i.e., Revolutions per Minute). Participants were 22 spin bowlers from either an Australia state youth squad or an academy in England. Results indicate that adopting a constraints-led approach can benefit younger, inexperienced bowlers, whilst a traditional approach may assist more skilled, older bowlers. The findings are discussed with regards to how they may inform the learning design of training programs by cricket coaches.

The Relationship Between University Culture and Climate and Research Scientists’ Spin-off Intentions

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their 'third mission', universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This chapter adopts an institutional perspective to understand how organizational characteristics affect research scientists' entrepreneurial intentions. We study the impact of university culture and climate on entrepreneurial intentions, thereby specifically focusing on intentions to spin off a company. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists' spin-off intentions. Furthermore, the presence of university role models positively affects research scientists' propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for 'third mission' related output show higher levels of spin-off intentions. This study has implications for both academics and practitioners, including university managers and policy makers.

Predicting a new phase (T′′) of two-dimensional transition metal di-chalcogenides and strain-controlled topological phase transition

Single layered transition metal dichalcogenides have attracted tremendous research interest due to their structural phase diversities. By using a global optimization approach, we have discovered a new phase of transition metal dichalcogenides (labelled as T′′), which is confirmed to be energetically, dynamically and kinetically stable by our first-principles calculations. The new T′′ MoS2 phase exhibits an intrinsic quantum spin Hall (QSH) effect with a nontrivial gap as large as 0.42 eV, suggesting that a two-dimensional (2D) topological insulator can be achieved at room temperature. Most interestingly, there is a topological phase transition simply driven by a small tensile strain of up to 2%. Furthermore, all the known MX2 (M = Mo or W; X = S, Se or Te) monolayers in the new T′′ phase unambiguously display similar band topologies and strain controlled topological phase transitions. Our findings greatly enrich the 2D families of transition metal dichalcogenides and offer a feasible way to control the electronic states of 2D topological insulators for the fabrication of high-speed spintronics devices.

Single household domestic water heater design and control utilising PV energy: The untapped energy storage solution

Photovoltaic (PV) panels and electric domestic water heater with storage (DWH) are widely used in households in many countries. However, DWH should be explored as an energy storage mechanism before batteries when households have excess PV energy. Through a residential case study in Queensland, Australia, this paper presents a new optimized design and control solution to reduce water heating costs by utilizing existing DWH energy storage capacity and increasing PV self-consumption for water heating. The solution is produced by evaluating the case study energy profile and numerically maximizing the use of PV for DWH. A conditional probability matrix for different solar insolation and hot water usage days is developed to test the solution. Compared to other tariffs, this solution shows cost reduction from 20.8% to 63.3% This new solution could encourage solar households move to a more economical and carbon neutral water heating method.

A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other

In this report, we describe a simple correction for multiple testing of single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with each other, on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs. This method provides a useful alternative to more computationally intensive permutation tests. Additionally, output from SNPSpD includes eigenvalues, principal-component coefficients, and factor "loadings" after varimax rotation, enabling the selection of a subset of SNPs that optimize the information in a genomic region.

Does the addition of Clonidine to lumbar nerve root blocks improve outcome? A randomised, prospective, single-blinded controlled pilot study

Purpose To evaluate if adding clonidine to a standard nerve root block containing local anaesthetic and steroid improved the outcome of patients with severe lumbar nerve root pain secondary to MRI proven lumbar disc prolapse. Methods We undertook a single blind, prospective, randomised controlled trial evaluating 100 consecutive patients with nerve root pain secondary to lumbar disc prolapse undergoing trans-foraminal epidural steroid injection either with or without the addition of clonidine. 50 patients were allocated to each arm of the study. The primary outcome measure was the avoidance of a second procedure- repeat injection or micro-discectomy surgery. Secondary outcome measures were also studied: pain scores for leg and back pain using a visual analogue scale (VAS), the Roland Morris Disability Questionnaire (RMDQ) and the Measure Your Own Medical Outcome Profile (MYMOP). Follow up was carried out at 6 weeks, 6 months and 1 year. Results No serious complications occurred. Of the 50 patients who received the addition of clonidine, 56% were classified as successful injections, with no further intervention required, as opposed to 40% who received the standard injection. This difference did not reach statistical significance (p=0.109, chi-squared test). All secondary measures showed no statistically significant differences between the groups except curiously, the standard group who had been classified as successful had better leg pain relief than the clonidine group (p=0.026) at 1 year. Conclusions This pilot study has shown a 16% treatment effect with adding clonidine to lumbar nerve root blocks and that it is a safe injectate for this purpose.

Single layer graphene film by ethanol chemical vapor deposition: Highly efficient growth and clean transfer method

The choice of ethanol (C2H5OH) as carbon source in the Chemical Vapor Deposition (CVD) of graphene on copper foils can be considered as an attractive alternative among the commonly used hydrocarbons, such as methane (CH4) [1]. Ethanol, a safe, low cost and easy handling liquid precursor, offers fast and efficient growth kinetics with the synthesis of fullyformed graphene films in just few seconds [2]. In previous studies of graphene growth from ethanol, various research groups explored temperature ranges lower than 1000 °C, usually reported for methane-assisted CVD. In particular, the 650–850 °C and 900 °C ranges were investigated, respectively for 5 and 30 min growth time [3, 4]. Recently, our group reported the growth of highly-crystalline, few-layer graphene by ethanol-CVD in hydrogen flow (1– 100 sccm) at high temperatures (1000–1070 °C) using growth times typical of CH4-assisted synthesis (10–30 min) [5]. Furthermore, a synthesis time between 20 and 60 s in the same conditions was explored too. In such fast growth we demonstrated that fully-formed graphene films can be grown by exposing copper foils to a low partial pressure of ethanol (up to 2 Pa) in just 20 s [6] and we proposed that the rapid growth is related to an increase of the Cu catalyst efficiency due weak oxidizing nature of ethanol. Thus, the employment of such liquid precursor, in small concentrations, together with a reduced time of growth and very low pressure leads to highly efficient graphene synthesis. By this way, the complete coverage of a copper catalyst surface with high spatial uniformity can be obtained in a considerably lower time than when using methane.

Association of the microRNA-Single Nucleotide Polymorphism rs2910164 in miR146a with sporadic breast cancer susceptibility: A case control study

Background Breast cancer (BC) is primarily considered a genetic disorder with a complex interplay of factors including age, gender, ethnicity, family history, personal history and lifestyle with associated hormonal and non-hormonal risk factors. The SNP rs2910164 in miR146a (a G to C polymorphism) was previously associated with increased risk of BC in cases with at least a single copy of the C allele in breast cancer, though results in other cancers and populations have shown significant variation. Methods In this study, we examined this SNP in an Australian sporadic breast cancer population of 160 cases and matched controls, with a replicate population of 403 breast cancer cases using High Resolution Melting. Results Our analysis indicated that the rs2910164 polymorphism is associated with breast cancer risk in both primary and replicate populations (p = 0.03 and 0.0013, respectively). In contrast to the results of familial breast cancer studies, however, we found that the presence of the G allele of rs2910164 is associated with increased cancer risk, with an OR of 1.77 (95% CI 1.40–2.23). Conclusions The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.