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Search Results: 1 - 10 of 200843 matches for " Stephen G. Hillier "
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Glucocorticoid Regulation of SLIT/ROBO Tumour Suppressor Genes in the Ovarian Surface Epithelium and Ovarian Cancer Cells
Rachel E. Dickinson, K. Scott Fegan, Xia Ren, Stephen G. Hillier, W. Colin Duncan
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027792
Abstract: The three SLIT ligands and their four ROBO receptors have fundamental roles in mammalian development by promoting apoptosis and repulsing aberrant cell migration. SLITs and ROBOs have emerged as candidate tumour suppressor genes whose expression is inhibited in a variety of epithelial tumours. We demonstrated that their expression could be negatively regulated by cortisol in normal ovarian luteal cells. We hypothesised that after ovulation the locally produced cortisol would inhibit SLIT/ROBO expression in the ovarian surface epithelium (OSE) to facilitate its repair and that this regulatory pathway was still present, and could be manipulated, in ovarian epithelial cancer cells. Here we examined the expression and regulation of the SLIT/ROBO pathway in OSE, ovarian cancer epithelial cells and ovarian tumour cell lines. Basal SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 expression was lower in primary cultures of ovarian cancer epithelial cells when compared to normal OSE (P<0.05) and in poorly differentiated SKOV-3 cells compared to the more differentiated PEO-14 cells (P<0.05). Cortisol reduced the expression of certain SLITs and ROBOs in normal OSE and PEO-14 cells (P<0.05). Furthermore blocking SLIT/ROBO activity reduced apoptosis in both PEO-14 and SKOV-3 tumour cells (P<0.05). Interestingly SLIT/ROBO expression could be increased by reducing the expression of the glucocorticoid receptor using siRNA (P<0.05). Overall our findings indicate that in the post-ovulatory phase one role of cortisol may be to temporarily inhibit SLIT/ROBO expression to facilitate regeneration of the OSE. Therefore this pathway may be a target to develop strategies to manipulate the SLIT/ROBO system in ovarian cancer.
Biological versus chronological ovarian age: implications for assisted reproductive technology
Carlo Alviggi, Peter Humaidan, Colin M Howles, Donald Tredway, Stephen G Hillier
Reproductive Biology and Endocrinology , 2009, DOI: 10.1186/1477-7827-7-101
Abstract: Literature searches supplemented with the authors' knowledge.Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells.Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.Over recent years
Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials
Sera L. Young, M. Jeffrey Wilson, Dennis Miller, Stephen Hillier
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003147
Abstract: Background Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem. Methodology In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica. Principal Findings Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma–atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles. Significance This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption.
The generation and damping of propagating MHD kink waves in the solar atmosphere
R. J. Morton,G. Verth,A. Hillier,R. Erdélyi
Physics , 2013, DOI: 10.1088/0004-637X/784/1/29
Abstract: The source of the non-thermal energy required for the heating of the upper solar atmosphere to temperatures in excess of a million degrees and the acceleration of the solar wind to hundreds of kilometres per second is still unclear. One such mechanism for providing the required energy flux is incompressible torsional Alfv\'en and kink magnetohydrodynamic (MHD) waves, which are magnetically dominated waves supported by the Sun's pervasive and complex magnetic field. In particular, propagating MHD kink waves have recently been observed to be ubiquitous throughout the solar atmosphere, but, until now, critical details of the transport of the kink wave energy throughout the Sun's atmosphere were unclear. Here, the ubiquity of the waves is exploited for statistical studies in the highly dynamic solar chromosphere. This large-scale investigation allows for the determination of the chromospheric kink wave velocity power spectra, a missing link necessary for determining the energy transport between the photosphere and corona. Crucially, the power spectra contains evidence for horizontal photospheric motions being the main mechanism for kink wave generation in the quiescent Sun. In addition, a comparison to measured coronal power spectra is provided, revealing frequency-dependent transmission profiles suggesting there is enhanced damping of kink waves in the lower corona.
A quantitative study of O stars in NGC2244 and the Mon OB2 association
F. Martins,L. Mahy,G. Rauw,D. J. Hillier
Physics , 2011, DOI: 10.1051/0004-6361/201117458
Abstract: Our goal is to determine the stellar and wind properties of seven O stars in the cluster NGC2244 and three O stars in the OB association MonOB2. These properties give us insight into the mass loss rates of O stars, allow us to check the validity of rotational mixing in massive stars, and to better understand the effects of the ionizing flux and wind mechanical energy release on the surrounding interstellar medium and its influence on triggered star formation. We collect optical and UV spectra of the target stars which are analyzed by means of atmosphere models computed with the code CMFGEN. The spectra of binary stars are disentangled and the components are studied separately. All stars have an evolutionary age less than 5 million years, with the most massive stars being among the youngest. Nitrogen surface abundances show no clear relation with projected rotational velocities. Binaries and single stars show the same range of enrichment. This is attributed to the youth and/or wide separation of the binary systems in which the components have not (yet) experienced strong interaction. A clear trend of larger enrichment in higher luminosity objects is observed, consistent with what evolutionary models with rotation predict for a population of O stars at a given age. We confirm the weakness of winds in late O dwarfs. In general, mass loss rates derived from UV lines are lower than mass loss rates obtained from Ha. The UV mass loss rates are even lower than the single line driving limit in the latest type dwarfs. These issues are discussed in the context of the structure of massive stars winds. The evolutionary and spectroscopic masses are in agreement above 25 Msun but the uncertainties are large. Below this threshold, the few late-type O stars studied here indicate that the mass discrepancy still seems to hold.
Local-entire cyclic cocycles for graded quantum field nets
Robin Hillier
Mathematics , 2013, DOI: 10.1007/s11005-013-0662-1
Abstract: In a recent paper we studied general properties of super-KMS functionals on graded quantum dynamical systems coming from graded translation-covariant quantum field nets over R, and we carried out a detailed analysis of these objects on certain models of superconformal nets. In the present article we show that these locally bounded functionals give rise to local-entire cyclic cocycles (generalized JLO cocycles), which are homotopy-invariant for a suitable class of perturbations. Thus we can associate meaningful noncommutative geometric invariants to those graded quantum dynamical systems.
Super-KMS functionals for graded-local conformal nets
Robin Hillier
Mathematics , 2012, DOI: 10.1007/s00023-014-0355-z
Abstract: Motivated by a few preceding papers and a question of R. Longo, we introduce super-KMS functionals for graded translation-covariant nets over R with superderivations, roughly speaking as a certain supersymmetric modification of classical KMS states on translation-covariant nets over R, fundamental objects in chiral algebraic quantum field theory. Although we are able to make a few statements concerning their general structure, most properties will be studied in the setting of specific graded-local (super-) conformal models. In particular, we provide a constructive existence and partial uniqueness proof of super-KMS functionals for the supersymmetric free field, for certain subnets, and for the super-Virasoro net with central charge c>= 3/2. Moreover, as a separate result, we classify bounded super-KMS functionals for graded-local conformal nets over S^1 with respect to rotations.
The common language of space: a way of looking at the social,economic and environmental functioning of cities on a common basis
The common language of space:a way of looking at the social,economic and environmental functioning of cities on a common basis

Bill Hillier,

环境科学学报(英文版) , 1999,
Abstract: This paper proposes that in addition to urban research which seeks to provide answers to policy questions, there is also a need for research which directly addresses the physical and spatial complexity of the built environment itself, and explores any effects it may in itself have on the functioning of the urban system. This type of research reflects the questions architects and urban designers typically ask, rather than those that preoccupy planners. For such research to be effective, the physical complexity variable must be controlled at the level at which real design decisions are made. "Space syntax' research attempts to do this by treating built environments as systems of space, analysing them "configurationally", and trying to bring to light their underlying patterns and structures. Results from space syntax research into many aspects of urban space and how it works show a consistency which suggests that analysing spacial structure can be a general means of investigating the structure and function of cities. It may, in effect, be the common language of the city.
Nanoscopic coexistence of magnetism and superconductivity in YBa2Cu3O6+x detected by MuSR
S. Sanna,G. Allodi,G. Concas,A. H. Hillier,R. De Renzi
Physics , 2004, DOI: 10.1103/PhysRevLett.93.207001
Abstract: We performed zero and transverse field MuSR experiments on a large number of YBa2Cu3O6+x samples. We detect coexistence of antiferro-type (AF) short range magnetism with superconductivity below T_f~10 K in compositions 0.37
What Do We Need to Know to Enhance the Environmental Sustainability of Agricultural Production? A Prioritisation of Knowledge Needs for the UK Food System
Lynn V. Dicks,Richard D. Bardgett,Jenny Bell,Tim G. Benton,Angela Booth,Jan Bouwman,Chris Brown,Ann Bruce,Paul J. Burgess,Simon J. Butler,Ian Crute,Frances Dixon,Caroline Drummond,Robert P. Freckleton,Maggie Gill,Andrea Graham,Rosie S. Hails,James Hallett,Beth Hart,Jon G. Hillier,John M. Holland,Jonathan N. Huxley,John S. I. Ingram,Vanessa King,Tom MacMillan,Daniel F. McGonigle,Carmel McQuaid,Tim Nevard,Steve Norman,Ken Norris,Catherine Pazderka,Inder Poonaji,Claire H. Quinn,Stephen J. Ramsden,Duncan Sinclair,Gavin M. Siriwardena,Juliet A. Vickery,Andrew P. Whitmore,William Wolmer,William J. Sutherland
Sustainability , 2013, DOI: 10.3390/su5073095
Abstract: Increasing concerns about global environmental change and food security have focused attention on the need for environmentally sustainable agriculture. This is agriculture that makes efficient use of natural resources and does not degrade the environmental systems that underpin it, or deplete natural capital stocks. We convened a group of 29 ‘practitioners’ and 17 environmental scientists with direct involvement or expertise in the environmental sustainability of agriculture. The practitioners included representatives from UK industry, non-government organizations and government agencies. We collaboratively developed a long list of 264 knowledge needs to help enhance the environmental sustainability of agriculture within the UK or for the UK market. We refined and selected the most important knowledge needs through a three-stage process of voting, discussion and scoring. Scientists and practitioners identified similar priorities. We present the 26 highest priority knowledge needs. Many of them demand integration of knowledge from different disciplines to inform policy and practice. The top five are about sustainability of livestock feed, trade-offs between ecosystem services at farm or landscape scale, phosphorus recycling and metrics to measure sustainability. The outcomes will be used to guide on-going knowledge exchange work, future science policy and funding.
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