906 research outputs found
Science Models as Value-Added Services for Scholarly Information Systems
The paper introduces scholarly Information Retrieval (IR) as a further
dimension that should be considered in the science modeling debate. The IR use
case is seen as a validation model of the adequacy of science models in
representing and predicting structure and dynamics in science. Particular
conceptualizations of scholarly activity and structures in science are used as
value-added search services to improve retrieval quality: a co-word model
depicting the cognitive structure of a field (used for query expansion), the
Bradford law of information concentration, and a model of co-authorship
networks (both used for re-ranking search results). An evaluation of the
retrieval quality when science model driven services are used turned out that
the models proposed actually provide beneficial effects to retrieval quality.
From an IR perspective, the models studied are therefore verified as expressive
conceptualizations of central phenomena in science. Thus, it could be shown
that the IR perspective can significantly contribute to a better understanding
of scholarly structures and activities.Comment: 26 pages, to appear in Scientometric
Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway
This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel
Thermodynamical Metrics and Black Hole Phase Transitions
An important phase transition in black hole thermodynamics is associated with
the divergence of the specific heat with fixed charge and angular momenta, yet
one can demonstrate that neither Ruppeiner's entropy metric nor Weinhold's
energy metric reveals this phase transition. In this paper, we introduce a new
thermodynamical metric based on the Hessian matrix of several free energy. We
demonstrate, by studying various charged and rotating black holes, that the
divergence of the specific heat corresponds to the curvature singularity of
this new metric. We further investigate metrics on all thermodynamical
potentials generated by Legendre transformations and study correspondences
between curvature singularities and phase transition signals. We show in
general that for a system with n-pairs of intensive/extensive variables, all
thermodynamical potential metrics can be embedded into a flat (n,n)-dimensional
space. We also generalize the Ruppeiner metrics and they are all conformal to
the metrics constructed from the relevant thermodynamical potentials.Comment: Latex, 25 pages, reference added, typos corrected, English polished
and the Hawking-Page phase transition clarified; to appear in JHE
Seasonality and trend in blood lead levels of New York State children
BACKGROUND: Environmental exposure to lead remains a significant health problem for children. The costs of lead exposure in children are estimated to be considerably more than other childhood diseases of environmental origin. While long-term trends in blood lead levels (BLLs) among children are declining, seasonal variation persists. Cross-sectional studies have found a peak in summer months. Part of this variation may be due to increased exposure to lead paint on window sills and through increased contact with soils containing lead during the summer. The current study represents the largest published population-based study on seasonality and trends in the BLLs of children to date. In addition, the results offer a comparison of recent data on seasonality of BLLs in New York State children, to studies conducted over the past three decades. METHODS: 262,687 New York State children born between 1994 and 1997 were screened for blood lead within 2 weeks of their first or second birthdays. Time series analyses of blood lead data from these children were conducted to study the seasonality and trends of BLLs. RESULTS: Children's blood lead values showed a distinct seasonal cycle on top of a long-term decreasing trend. The geometric mean BLL declined by about 24% for children born between 1994 and 1997. The prevalence of elevated BLLs in two-year-olds was almost twice that in one-year-olds over the time period. Nearly twice as many children had elevated BLLs in the late summer compared to late winter/early spring. In this and previous cross-sectional studies, the amount of seasonality as a proportion of the mean ranged between 15% and 30%. CONCLUSION: Pediatricians should be aware of the seasonality of BLLs. For example, if a two-year-old receives a borderline result during the winter, it is possible that the levels would have been higher if he had been tested during the summer. However, physicians should continue to screen children at their normally scheduled well-child visits rather than delaying until summertime and possibly postponing the discovery of an elevated BLL. Age, season, and time trends still need to be considered in lead studies and result interpretation
Argumentation in school science : Breaking the tradition of authoritative exposition through a pedagogy that promotes discussion and reasoning
The value of argumentation in science education has become internationally recognised and has been the subject of many research studies in recent years. Successful introduction of argumentation activities in learning contexts involves extending teaching goals beyond the understanding of facts and concepts, to include an emphasis on cognitive and metacognitive processes, epistemic criteria and reasoning. The authors focus on the difficulties inherent in shifting a tradition of teaching from one dominated by authoritative exposition to one that is more dialogic, involving small-group discussion based on tasks that stimulate argumentation. The paper builds on previous research on enhancing the quality of argument in school science, to focus on how argumentation activities have been designed, with appropriate strategies, resources and modelling, for pedagogical purposes. The paper analyses design frameworks, their contexts and lesson plans, to evaluate their potential for enhancing reasoning through foregrounding the processes of argumentation. Examples of classroom dialogue where teachers adopt the frameworks/plans are analysed to show how argumentation processes are scaffolded. The analysis shows that several layers of interpretation are needed and these layers need to be aligned for successful implementation. The analysis serves to highlight the potential and limitations of the design frameworks
Characteristic Evolution and Matching
I review the development of numerical evolution codes for general relativity
based upon the characteristic initial value problem. Progress in characteristic
evolution is traced from the early stage of 1D feasibility studies to 2D
axisymmetric codes that accurately simulate the oscillations and gravitational
collapse of relativistic stars and to current 3D codes that provide pieces of a
binary black hole spacetime. Cauchy codes have now been successful at
simulating all aspects of the binary black hole problem inside an artificially
constructed outer boundary. A prime application of characteristic evolution is
to extend such simulations to null infinity where the waveform from the binary
inspiral and merger can be unambiguously computed. This has now been
accomplished by Cauchy-characteristic extraction, where data for the
characteristic evolution is supplied by Cauchy data on an extraction worldtube
inside the artificial outer boundary. The ultimate application of
characteristic evolution is to eliminate the role of this outer boundary by
constructing a global solution via Cauchy-characteristic matching. Progress in
this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note:
updated version of arXiv:gr-qc/050809
Isolated and dynamical horizons and their applications
Over the past three decades, black holes have played an important role in
quantum gravity, mathematical physics, numerical relativity and gravitational
wave phenomenology. However, conceptual settings and mathematical models used
to discuss them have varied considerably from one area to another. Over the
last five years a new, quasi-local framework was introduced to analyze diverse
facets of black holes in a unified manner. In this framework, evolving black
holes are modeled by dynamical horizons and black holes in equilibrium by
isolated horizons. We review basic properties of these horizons and summarize
applications to mathematical physics, numerical relativity and quantum gravity.
This paradigm has led to significant generalizations of several results in
black hole physics. Specifically, it has introduced a more physical setting for
black hole thermodynamics and for black hole entropy calculations in quantum
gravity; suggested a phenomenological model for hairy black holes; provided
novel techniques to extract physics from numerical simulations; and led to new
laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte
Large Scale Structure of the Universe
Galaxies are not uniformly distributed in space. On large scales the Universe
displays coherent structure, with galaxies residing in groups and clusters on
scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of
galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space,
known as voids, contain very few galaxies and span the volume in between these
structures. This observed large scale structure depends both on cosmological
parameters and on the formation and evolution of galaxies. Using the two-point
correlation function, one can trace the dependence of large scale structure on
galaxy properties such as luminosity, color, stellar mass, and track its
evolution with redshift. Comparison of the observed galaxy clustering
signatures with dark matter simulations allows one to model and understand the
clustering of galaxies and their formation and evolution within their parent
dark matter halos. Clustering measurements can determine the parent dark matter
halo mass of a given galaxy population, connect observed galaxy populations at
different epochs, and constrain cosmological parameters and galaxy evolution
models. This chapter describes the methods used to measure the two-point
correlation function in both redshift and real space, presents the current
results of how the clustering amplitude depends on various galaxy properties,
and discusses quantitative measurements of the structures of voids and
filaments. The interpretation of these results with current theoretical models
is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets,
Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume
editor W. C. Keel, v2 includes additional references, updated to match
published versio
Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses
The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens
Quantization of Midisuperspace Models
We give a comprehensive review of the quantization of midisuperspace models.
Though the main focus of the paper is on quantum aspects, we also provide an
introduction to several classical points related to the definition of these
models. We cover some important issues, in particular, the use of the principle
of symmetric criticality as a very useful tool to obtain the required
Hamiltonian formulations. Two main types of reductions are discussed: those
involving metrics with two Killing vector fields and spherically symmetric
models. We also review the more general models obtained by coupling matter
fields to these systems. Throughout the paper we give separate discussions for
standard quantizations using geometrodynamical variables and those relying on
loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit
- …