1,633 research outputs found
A dependent pathway of gene functions leading to chromosome segregation in Saccharomyces cerevisiae.
Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network
BACKGROUND
It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems.
RESULTS
Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system.
CONCLUSION
We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data
Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction : systematic review and economic evaluation
Background
The blockage of a coronary artery (coronary thrombosis) can lead to a heart attack (acute myocardial infarction). There are several ways of trying to overcome this blockage. The methods include drug treatment to dissolve the clot (thrombolysis) and physical intervention, either by passing a catheter into the affected artery [angioplasty or percutaneous coronary intervention (PCI)], or bypassing the blocked section by cardiac surgery [coronary artery bypass grafting (CABG)].
Thrombolysis can be given in the community before the patient is sent to hospital, or delayed until after admission. Prehospital thrombolysis is not common in the UK.
Immediate angioplasty is not routinely available in the UK at present; it is much more common in the USA.
Objectives
To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective.
Methods
This report was based on a systematic review of the evidence of clinical effectiveness and an economic analysis of cost-effectiveness based on the clinical review and on cost data from published sources and de novo data collection.
Data sources
The search strategy searched six electronic databases (including Medline, Cochrane Library and EMBASE), with English-language limits, for the periods up to December 2002. Bibliographies of related papers were assessed for relevant studies and experts contacted for advice and peer review, and to identify additional published and unpublished references.
Study selection
For clinical effectiveness, a comprehensive review of randomised controlled trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data for effectiveness safety in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. They were used to assess the implications of wider diffusion of the technology away from major centres.
Data extraction
Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of systematic reviews, RCTs, controlled clinical trials and economic studies was assessed using criteria recommended by the NHS Centre for Reviews and Dissemination (University of York).
Study synthesis
Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months).
Results and conclusion
Number and quality of studies, and summary of benefits
There were several good-quality systematic reviews, including a Cochrane review, as well as an individual patient meta-analysis and a number of recent trials not included in the reviews. The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with PCI, with the difference being due to haemorrhagic stroke. The need for CABG is reduced by about one-third, from 13.2% to 8.4%.
Caution is needed in interpreting the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. One good quality study from France showed that prehospital thrombolysis with PCI in those in whom thrombolysis failed was as good as universal PCI. Research on thrombolysis followed by PCI, known as facilitated PCI, is underway, but results are not yet available. Further caveats are needed. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than 1 hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI.
Cost-effectiveness
If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost and an incremental cost per unit change in health status under the ÂŁ30,000 threshold in most instances. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. The model is not particularly sensitive to variations in probabilities from the clinical effectiveness analysis.
However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve.
A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, could be used. In rural areas, one option could be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures.
Need for further research
There is a need for economic data on the long-term consequences of the treatment, the quality of life of patients after treatment and the effects of PCI following thrombolysis failure
Conformally coupled supermultiplets in four and five dimensions
We obtain by superfield methods the exceptional representations of the
OSp(2N/4,R) and SU(2,2/1) superalgebras which extend to supersingletons of
SU(2,2/2N) and F(4), respectively. These representations describe
superconformally coupled multiplets and appear in three- and four-dimensional
superconformal field theories which are holographic descriptions of certain
anti-de Sitter supergravities
Complex networks theory for analyzing metabolic networks
One of the main tasks of post-genomic informatics is to systematically
investigate all molecules and their interactions within a living cell so as to
understand how these molecules and the interactions between them relate to the
function of the organism, while networks are appropriate abstract description
of all kinds of interactions. In the past few years, great achievement has been
made in developing theory of complex networks for revealing the organizing
principles that govern the formation and evolution of various complex
biological, technological and social networks. This paper reviews the
accomplishments in constructing genome-based metabolic networks and describes
how the theory of complex networks is applied to analyze metabolic networks.Comment: 13 pages, 2 figure
On duality symmetries of supergravity invariants
The role of duality symmetries in the construction of counterterms for
maximal supergravity theories is discussed in a field-theoretic context from
different points of view. These are: dimensional reduction, the question of
whether appropriate superspace measures exist and information about non-linear
invariants that can be gleaned from linearised ones. The former allows us to
prove that F-term counterterms cannot be E7(7)-invariant in D=4, N=8
supergravity or E6(6)-invariant in D=5 maximal supergravity. This is confirmed
by the two other methods which can also be applied to D=4 theories with fewer
supersymmetries and allow us to prove that N=6 supergravity is finite at three
and four loops and that N=5 supergravity is three-loop finite.Comment: Clarification of arguments and their consistency with higher
dimensional divergences added, e.g. we prove the 5D 4L non-renormalisation
theorem. The 4L N=6 divergence is also ruled out. References adde
Global organization of metabolic fluxes in the bacterium, Escherichia coli
Cellular metabolism, the integrated interconversion of thousands of metabolic
substrates through enzyme-catalyzed biochemical reactions, is the most
investigated complex intercellular web of molecular interactions. While the
topological organization of individual reactions into metabolic networks is
increasingly well understood, the principles governing their global functional
utilization under different growth conditions pose many open questions. We
implement a flux balance analysis of the E. coli MG1655 metabolism, finding
that the network utilization is highly uneven: while most metabolic reactions
have small fluxes, the metabolism's activity is dominated by several reactions
with very high fluxes. E. coli responds to changes in growth conditions by
reorganizing the rates of selected fluxes predominantly within this high flux
backbone. The identified behavior likely represents a universal feature of
metabolic activity in all cells, with potential implications to metabolic
engineering.Comment: 15 pages 4 figure
Hierarchical Organization in Complex Networks
Many real networks in nature and society share two generic properties: they
are scale-free and they display a high degree of clustering. We show that these
two features are the consequence of a hierarchical organization, implying that
small groups of nodes organize in a hierarchical manner into increasingly large
groups, while maintaining a scale-free topology. In hierarchical networks the
degree of clustering characterizing the different groups follows a strict
scaling law, which can be used to identify the presence of a hierarchical
organization in real networks. We find that several real networks, such as the
World Wide Web, actor network, the Internet at the domain level and the
semantic web obey this scaling law, indicating that hierarchy is a fundamental
characteristic of many complex systems
AdS/SCFT in Superspace
A discussion of the AdS/CFT correspondence in IIB is given in a superspace
context. The main emphasis is on the properties of SCFT correlators on the
boundary which are studied using harmonic superspace techniques. These
techniques provide the easiest way of implementing the superconformal Ward
identities. The Ward identities, together with analyticity, can be used to give
a compelling argument in support of the non-renormalisation theorems for two-
and three-point functions, and to establish the triviality of extremal and
next-to-extremal correlation functions. The OPE in is also briefly discussed.Comment: 10 pages; talk given by PSH at 2nd Gursey Memorial Conference, June
200
- âŠ