Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.

Control of morphology and nucleation density of iron oxide nanostructures by electric conditions on iron surfaces exposed to reactive oxygen plasmas

The possibility to control the morphology and nucleation density of quasi-one-dimensional, single-crystalline α -Fe2 O3 nanostructures by varying the electric potential of iron surfaces exposed to reactive oxygen plasmas is demonstrated experimentally. A systematic increase in the oxygen ion flux through rf biasing of otherwise floating substrates and then an additional increase of the ion/neutral density resulted in remarkable structural transformations of straight nanoneedles into nanowires with controlled tapering/aspect ratio and also in larger nucleation densities. Multiscale numerical simulations relate the microscopic ion flux topographies to the nanostructure nucleation and morphological evolution. This approach is applicable to other metal-oxide nanostructures.

Management of a high grade pan stage schedule to reduce the steam consumption

MOST PAN stages in Australian factories use only five or six batch pans for the high grade massecuite production and operate these in a fairly rigid repeating production schedule. It is common that some of the pans are of large dropping capacity e.g. 150 to 240 t. Because of the relatively small number and large sizes of the pans, steam consumption varies widely through the schedule, often by ±30% about the mean value. Large fluctuations in steam consumption have implications for the steam generation/condensate management of the factory and the evaporators when bleed vapour is used. One of the objectives of a project to develop a supervisory control system for a pan stage is to (a) reduce the average steam consumption and (b) reduce the variation in the steam consumption. The operation of each of the high grade pans within the schedule at Macknade Mill was analysed to determine the idle (or buffer) time, time allocations for essential but unproductive operations (e.g. pan turn round, charging, slow ramping up of steam rates on pan start etc.), and productive time i.e. the time during boil-on of liquor and molasses feed. Empirical models were developed for each high grade pan on the stage to define the interdependence of the production rate and the evaporation rate for the different phases of each pan’s cycle. The data were analysed in a spreadsheet model to try to reduce and smooth the total steam consumption. This paper reports on the methodology developed in the model and the results of the investigations for the pan stage at Macknade Mill. It was found that the operation of the schedule severely restricted the ability to reduce the average steam consumption and smooth the steam flows. While longer cycle times provide increased flexibility the steam consumption profile was changed only slightly. The ability to cut massecuite on the run among pans, or the use of a high grade seed vessel, would assist in reducing the average steam consumption and the magnitude of the variations in steam flow.

Experiences with control of evaporators using extensive vapour bleeding

FOR SUGAR factories with cogeneration plants major changes to the process stations have been undertaken to reduce the consumption of exhaust steam from the turbines and maximise the generated power. In many cases the process steam consumption has been reduced from greater than 52% on cane to ~40% on cane. The main changes have been to install additional evaporation area at the front of the set, operate the pan stages on vapour from No 1 or No 2 effects and undertake juice heating using vapour bleed from evaporators as far down the set as the penultimate stage. Operationally, one of the main challenges has been to develop a control system for the evaporators that addresses the objectives of juice processing rate (throughput) and steam economy, while producing syrup consistently at the required brix and providing an adequate and consistent vapour pressure for the pan stage operations. The cyclic demand for vapour by batch pans causes process disturbances through the evaporator set and these must be regulated in an effective manner to satisfy the above list of objectives for the evaporator station. The impact of the cyclic pan stage vapour demand has been modelled to define the impact on juice rate, steam economy, syrup brix and head space pressures in the evaporators. Experiences with the control schemes used at Pioneer and Rocky Point Mills are discussed. For each factory the paper provides information on (a) the control system used, the philosophy behind the control system and experiences in reaching the current system for control (b) the performance of the control system to handle the disturbances imposed by the pan stage and operate within other constraints of the factory (c) deficiencies in the current system and plans for further improvements. Other processing changes to boost the performance of the evaporators are also discussed.

Deterministic control of plasma-assembled self-organized Ge/Si quantum dot arrays

Self-assembly of size-uniform and spatially ordered quantum dot (QD) arrays is one of the major challenges in the development of the new generation of semiconducting nanoelectronic and photonic devices. Assembly of Ge QD (in the ∼5-20 nm size range) arrays from randomly generated position and size-nonuniform nanodot patterns on plasma-exposed Si (100) surfaces is studied using hybrid multiscale numerical simulations. It is shown, by properly manipulating the incoming ion/neutral flux from the plasma and the surface temperature, the uniformity of the nanodot size within the array can be improved by 34%-53%, with the best improvement achieved at low surface temperatures and high external incoming fluxes, which are intrinsic to plasma-aided processes. Using a plasma-based process also leads to an improvement (∼22% at 700 K surface temperature and 0.1 MLs incoming flux from the plasma) of the spatial order of a randomly sampled nanodot ensemble, which self-organizes to position the dots equidistantly to their neighbors within the array. Remarkable improvements in QD ordering and size uniformity can be achieved at high growth rates (a few nms) and a surface temperature as low as 600 K, which broadens the range of suitable substrates to temperature-sensitive ultrathin nanofilms and polymers. The results of this study are generic, can also be applied to nonplasma-based techniques, and as such contributes to the development of deterministic strategies of nanoassembly of self-ordered arrays of size-uniform QDs, in the size range where nanodot ordering cannot be achieved by presently available pattern delineation techniques.

A control theoretic paradigm for cell signaling networks : a simple complexity for a sensitive robustness

The fields of molecular biology and cell biology are being flooded with complex genomic and proteomic datasets of large dimensions. We now recognize that each molecule in the cell and tissue can no longer be viewed as an isolated entity. Instead, each molecule must be considered as one member of an interacting network. Consequently, there is an urgent need for mathematical models to understand the behavior of cell signaling networks in health and in disease.

Effective control of ion fluxes over large areas by magnetic fields : from narrow beams to highly uniform fluxes

An effective control of the ion current distribution over large-area (up to 103 cm2) substrates with the magnetic fields of a complex structure by using two additional magnetic coils installed under the substrate exposed to vacuum arc plasmas is demonstrated. When the magnetic field generated by the additional coils is aligned with the direction of the magnetic field generated by the guiding and focusing coils of the vacuum arc source, a narrow ion density distribution with the maximum current density 117 A m-2 is achieved. When one of the additional coils is set to generate the magnetic field of the opposite direction, an area almost uniform over the substrate of 103 cm2 ion current distribution with the mean value of 45 A m-2 is achieved. Our findings suggest that the system with the vacuum arc source and two additional magnetic coils can be effectively used for the effective, high throughput, and highly controllable plasma processing.

Control and diagnostics of inductively coupled plasmas for chemical vapour deposition of nanocomposite carbon nitride-based films

Control and diagnostics of low-frequency (∼ 500 kHz) inductively coupled plasmas for chemical vapor deposition (CVD) of nano-composite carbon nitride-based films is reported. Relation between the discharge control parameters, plasma electron energy distribution/probability functions (EEDF/EEPF), and elemental composition in the deposited C-N based thin films is investigated. Langmuir probe technique is employed to monitor the plasma density and potential, effective electron temperature, and EEDFs/EEPFs in Ar + N2 + CH4 discharges. It is revealed that varying RF power and gas composition/pressure one can engineer the EEDFs/EEPFs to enhance the desired plasma-chemical gas-phase reactions thus controlling the film chemical structure. Auxiliary diagnostic tools for study of the RF power deposition, plasma composition, stability, and optical emission are discussed as well.

Doctoral research training : encouraging timely completion – case study reflections of one university on how it supports a vibrant research training culture

This is a case study of a young university striving to generate and sustain a vibrant Research Training culture. The university’s research training framework is informed by a belief in a project management approach to achieving successful research candidature. This has led to the definition and reporting of key milestones during candidature. In turn, these milestones have generated a range of training programs to support Higher Degree Research (HDR) students to meet these milestones in a timely fashion. Each milestone focuses on a specific set of skills blended with supporting the development of different parts of the doctoral thesis. Data on student progress and completion has provided evidence in highlighting the role that the milestones and training are playing in supporting timely completion. A university-wide reporting cycle generated data on the range of workshops and training provided to Higher Degree Research students and supervisors. The report provided details of thesis topic and format, as well as participation in research training events and participant evaluation of those events. Analysis of the data led to recommendations and comments on the strengths and weaknesses of the current research training program. Discussion considered strategies and drivers for enhancements into the future. In particular, the paper reflects on the significant potential role of centrally curated knowledge systems to support HDR student and supervisor access, and engagement and success. The research training program was developed using blended learning as a model. It covered face-to-face workshops as well as online modules. These were supplemented by web portals that offered a range of services to inform and educate students and supervisors and included opportunities for students to interact with each other. Topics ranged from the research life cycle, writing and publication, ethics, managing research data, managing copyright, and project management to use of software and the University’s Code of Conduct for Research. The challenges discussed included: How to reach off campus students and those studying in external modes? How best to promote events to potential participants? How long and what format is best for face-to-face sessions? What online resources best supplement face-to-face offerings? Is there a place for peer-based learning and what form should this take? These questions are raised by a relatively young university seeking to build and sustain a vibrant research culture. The rapid growth in enrolments in recent years has challenged previous one-to-one models of support. This review of research training is timely in seeking strategies to address changing research training support capacity and student needs. Part of the discussion will focus on supervisory training, noting that good supervision is the one remaining place where one-to-one support is provided. Ensuring that supervisors are appropriately equipped to address student expectations is considered in the context of the research training provisions. The paper concludes with reflection on the challenges faced, and recommended ways forward as the number of research students grows into the future.

Achieving transparency in carbon labelling for construction materials – Lessons from current assessment standards and carbon labels

The construction industry is one of the largest sources of carbon emissions. Manufacturing of raw materials, such as cement, steel and aluminium, is energy intensive and has considerable impact on carbon emissions level. Due to the rising recognition of global climate change, the industry is under pressure to reduce carbon emissions. Carbon labelling schemes are therefore developed as meaningful yardsticks to measure and compare carbon emissions. Carbon labelling schemes can help switch consumer-purchasing habits to low-carbon alternatives. However, such switch is dependent on a transparent scheme. The principle of transparency is highlighted in all international greenhouse gas (GHG) standards, including the newly published ISO 14067: Carbon footprint of products – requirements and guidelines for quantification and communication. However, there are few studies which systematically investigate the transparency requirements in carbon labelling schemes. A comparison of five established carbon labelling schemes, namely the Singapore Green Labelling Scheme, the CarbonFree (the U.S.), the CO2 Measured Label and the Reducing CO2 Label (UK), the CarbonCounted (Canada), and the Hong Kong Carbon Labelling Scheme is therefore conducted to identify and investigate the transparency requirements. The results suggest that the design of current carbon labels have transparency issues relating but not limited to the use of a single sign to represent the comprehensiveness of the carbon footprint. These transparency issues are partially caused by the flexibility given to select system boundary in the life cycle assessment (LCA) methodology to measure GHG emissions. The primary contribution of this study to the construction industry is to reveal the transparency requirements from international GHG standards and carbon labels for construction products. The findings also offer five key strategies as practical implications for the global community to improve the performance of current carbon labelling schemes on transparency.

The effects of sleep restriction on executive inhibitory control and affect in young adults

Purpose: Young adults regularly experience restricted sleep due to a range of social, educational and vocational commitments. Evidence suggests that extended periods of sleep deprivation negatively impact affective and inhibitory control mechanisms leading to behavioural consequences such as increased emotional reactivity and impulsive behaviour. It is less clear whether acute periods of restricted sleep produce the same behavioural consequences. Methods: Nineteen young adults (m = 8, f = 12) with habitual late bed-time (after 22:30 h) and wake-time (after 06:30 h) completed a range of objective and subjective measures assessing sleepiness (Psychomotor Vigilance Task, Karolinska Sleepiness Scale), inhibitory control (Emotional Go/No-go Task and a Balloon Analog Risk Task) and affect (Positive and Negative Affective Schedule). Testing was counterbalanced across participants, and occurred on two occasions once following restricted sleep and once following habitual sleep one week apart. Results: Compared to habitual sleep, sleep restriction produced significantly slower performance on the Psychomotor Vigilance Task, and higher subjective ratings of sleepiness on the Karolinska Sleepiness Scale. Sleep restriction also caused a significant decrease in positive affect, but no change in negative affect on the Affective Schedule. Inhibitory control efficiency was significantly differentiated, with participants showing an increase in risk taking on the Balloon Analog Risk Task, but there was no evidence of increased reactivity to negative stimuli on the Emotional Go/No-go task. Conclusions: Results suggest that even acute periods of sleep loss may cause deficits in affective experiences and increase impulsive and potentially high risk behaviour in young adults.

Three-dimensional off-design numerical analysis of an organic Rankine cycle radial-inflow turbine

Optimisation of organic Rankine cycles(ORCs for binary cycle applications could play a major role in determining the competitiveness of low to moderate renewable sources. An important aspect of the optimisation is to maximise the turbine output power for a given resource. This requires careful attention to the turbine design notably through numerical simulations. Challenges in the numerical modelling of radial-inflow turbines using high-density working fluids still need to be addressed in order to improve the turbine design and better optimise ORCs. Thispaper presents preliminary 3D numerical simulations of a high-density radial-inflow ORC turbine in sensible geothermal conditions. Following extensive investigation of the operating conditions and thermodynamic cycle analysis, therefrigerant R143a is chosen as the high-density working fluid. The 1D design of the candidate radial-inflow turbine is presented in details. Furthermore, commercially-available software Ansys-CFX is used to perform preliminary steady-state 3D CFD simulations of the candidate R143a radial-inflow turbine for a number of operating conditions including off-design conditions. The real-gas properties are obtained using the Peng–Robinson equations of state.The thermodynamic ORC cycle is presented. The preliminary design created using dedicated radial-inflow turbine software Concepts-Rital is discussed and the 3D CFD results are presented and compared against the meanline analysis.

Evidence of a conserved role for Chlamydia HtrA in the replication phase of the chlamydial developmental cycle

Identification of the HtrA inhibitor JO146 previously enabled us to demonstrate an essential function for HtrA during the mid-replicative phase of the Chlamydia trachomatis developmental cycle. Here we extend our investigations to other members of the Chlamydia genus. C. trachomatis isolates with distinct replicative phase growth kinetics showed significant loss of viable infectious progeny after HtrA was inhibited during the replicative phase. Mid-replicative phase addition of JO146 was also significantly detrimental to Chlamydia pecorum, Chlamydia suis and Chlamydia cavie. These data combined indicate that HtrA has a conserved critical role during the replicative phase of the chlamydial developmental cycle.

Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

Awards before and after the Nobel Prize : a Matthew effect and/or a ticket to one's own funeral?

The primary aim of this descriptive exploration of scientists’ life cycle award patterns is to evaluate whether awards breed further awards and identify researcher experiences after reception of the Nobel Prize. To achieve this goal, we collected data on the number of awards received each year for 50 years before and after Nobel Prize reception by all 1901–2000 Nobel laureates in physics, chemistry, and medicine or physiology. Our results indicate an increasing rate of awards before Nobel reception, reaching the summit precisely in the year of the Nobel Prize. After this pinnacle year, awards drop sharply. This result is confirmed by separate analyses of three different disciplines and by a random-effects negative binomial regression model. Such an effect, however, does not emerge for more recent Nobel laureates (1971–2000). In addition, Nobelists in medicine or physiology generate more awards shortly before and after prize reception, whereas laureates in chemistry attract more awards as time progresses.