677 research outputs found
Independence and Accountability of Monetary and Fiscal Policy Committees
The democratic accountability of policymaking institutions which are autonomous within delegated mandates has not received as much attention as their independence. We analyze in a theoretical model the effects of accountability in the form of possible overriding of economic policy decisions by the government under different degrees of independence of expert committees conducting monetary and fiscal policy. The equilibrium outcomes of such alternative institution-design frameworks are compared according to key macroeconomic performance criteria. Our results stress the trade-off between anchoring inflation expectations on target and output stabilization that is not solved with accountability. --Independence,accountability,monetary policy,fiscal policy,expert committees,institution design
Independence and Accountability of Monetary and Fiscal Policy Committees
The democratic accountability of policymaking institutions which are autonomous within delegated mandates has not received as much attention as their independence. We analyze in a theoretical model the effects of accountability inthe form of possible overriding of economic policy decisions by the government under different degrees of independence of expert committees conducting monetary and fiscal policy. The equilibrium outcomes of such alternative institution-design frameworks are compared according to key macroeconomic performance criteria. Our results stress the trade-off between anchoring inflation expectations on target and output stabilization that is not solved with accountability.independence, accountability, monetary policy, fiscal policy, expert committees, institution design
Computational Studies on the Evolution of Metabolism
Living organisms throughout evolution have developed desired properties, such as the ability
of maintaining functionality despite changes in the environment or their inner structure, the
formation of functional modules, from metabolic pathways to organs, and most essentially
the capacity to adapt and evolve in a process called natural selection. It can be observed in
the metabolic networks of modern organisms that many key pathways such as the citric acid
cycle, glycolysis, or the biosynthesis of most amino acids are common to all of them.
Understanding the evolutionary mechanisms behind this development of complex biological
systems is an intriguing and important task of current research in biology as well as artificial
life. Several competing hypotheses for the formation of metabolic pathways and the mecha-
nisms that shape metabolic networks have been discussed in the literature, each of which finds
support from comparative analysis of extant genomes. However, while being powerful tools
for the investigation of metabolic evolution, these traditional methods do not allow to look
back in evolution far enough to the time when metabolism had to emerge and evolve to the
form we can observe today. To this end, simulation studies have been introduced to discover
the principles of metabolic evolution and the sources for the emergence of metabolism prop-
erties. These approaches differ considerably in the realism and explicitness of the underlying
models. A difficult trade-off between realism and computational feasibility has to be made
and further modeling decisions on many scales have to be taken into account, requiring the
combination of knowledge from different fields such as chemistry, physics, biology and last
but not least also computer science.
In this thesis, a novel computational model for the in silico evolution of early metabolism
is introduced. It comprises all the components on different scales to resemble a situation of
evolving metabolic protocells in an RNA-world. Therefore, the model contains a minimal
RNA-based genetics and an evolving metabolism of catalytic ribozymes that manipulate a
rich underlying chemistry. To allow the metabolic organization to escape from the confines
of the chemical space set by the initial conditions of the simulation and in general an open-
ended evolution, an evolvable sequence-to-function map is used. At the heart of the metabolic
subsystem is a graph-based artificial chemistry equipped with a built-in thermodynamics. The
generation of the metabolic reaction network is realized as a rule-based stochastic simulation.
The necessary reaction rates are calculated from the chemical graphs of the reactants on
the fly. The selection procedure among the population of protocells is based on the optimal metabolic yield of the protocells, which is computed using flux balance analysis.
The introduced computational model allows for profound investigations of the evolution of
early metabolism and the underlying evolutionary mechanisms. One application in this thesis
is the study of the formation of metabolic pathways. Therefore, four established hypothe-
ses, namely the backwards evolution, forward evolution, patchwork evolution and the shell
hypothesis, are discussed within the realms of this in silico evolution study. The metabolic
pathways of the networks, evolved in various simulation runs, are determined and analyzed
in terms of their evolutionary direction. The simulation results suggest that the seemingly
mutually exclusive hypotheses may well be compatible when considering that different pro-
cesses dominate different phases in the evolution of a metabolic system. Further, it is found
that forward evolution shapes the metabolic network in the very early steps of evolution. In
later and more complex stages, enzyme recruitment supersedes forward evolution, keeping a
core set of pathways from the early phase. Backward evolution can only be observed under
conditions of steady environmental change. Additionally, evolutionary history of enzymes
and metabolites were studied on the network level as well as for single instances, showing a
great variety of evolutionary mechanisms at work.
The second major focus of the in silico evolutionary study is the emergence of complex system
properties, such as robustness and modularity. To this end several techniques to analyze the
metabolic systems were used. The measures for complex properties stem from the fields of
graph theory, steady state analysis and neutral network theory. Some are used in general
network analysis and others were developed specifically for the purpose introduced in this
work. To discover potential sources for the emergence of system properties, three different
evolutionary scenarios were tested and compared. The first two scenarios are the same as
for the first part of the investigation, one scenario of evolution under static conditions and
one incorporating a steady change in the set of ”food” molecules. A third scenario was
added that also simulates a static evolution but with an increased mutation rate and regular
events of horizontal gene transfer between protocells of the population. The comparison of all
three scenarios with real world metabolic networks shows a significant similarity in structure
and properties. Among the three scenarios, the two static evolutions yield the most robust
metabolic networks, however, the networks evolved under environmental change exhibit their
own strategy to a robustness more suited to their conditions. As expected from theory,
horizontal gene transfer and changes in the environment seem to produce higher degrees
of modularity in metabolism. Both scenarios develop rather different kinds of modularity,
while horizontal gene transfer provides for more isolated modules, the modules of the second
scenario are far more interconnected
Computational Studies on the Evolution of Metabolism
Living organisms throughout evolution have developed desired properties, such as the ability
of maintaining functionality despite changes in the environment or their inner structure, the
formation of functional modules, from metabolic pathways to organs, and most essentially
the capacity to adapt and evolve in a process called natural selection. It can be observed in
the metabolic networks of modern organisms that many key pathways such as the citric acid
cycle, glycolysis, or the biosynthesis of most amino acids are common to all of them.
Understanding the evolutionary mechanisms behind this development of complex biological
systems is an intriguing and important task of current research in biology as well as artificial
life. Several competing hypotheses for the formation of metabolic pathways and the mecha-
nisms that shape metabolic networks have been discussed in the literature, each of which finds
support from comparative analysis of extant genomes. However, while being powerful tools
for the investigation of metabolic evolution, these traditional methods do not allow to look
back in evolution far enough to the time when metabolism had to emerge and evolve to the
form we can observe today. To this end, simulation studies have been introduced to discover
the principles of metabolic evolution and the sources for the emergence of metabolism prop-
erties. These approaches differ considerably in the realism and explicitness of the underlying
models. A difficult trade-off between realism and computational feasibility has to be made
and further modeling decisions on many scales have to be taken into account, requiring the
combination of knowledge from different fields such as chemistry, physics, biology and last
but not least also computer science.
In this thesis, a novel computational model for the in silico evolution of early metabolism
is introduced. It comprises all the components on different scales to resemble a situation of
evolving metabolic protocells in an RNA-world. Therefore, the model contains a minimal
RNA-based genetics and an evolving metabolism of catalytic ribozymes that manipulate a
rich underlying chemistry. To allow the metabolic organization to escape from the confines
of the chemical space set by the initial conditions of the simulation and in general an open-
ended evolution, an evolvable sequence-to-function map is used. At the heart of the metabolic
subsystem is a graph-based artificial chemistry equipped with a built-in thermodynamics. The
generation of the metabolic reaction network is realized as a rule-based stochastic simulation.
The necessary reaction rates are calculated from the chemical graphs of the reactants on
the fly. The selection procedure among the population of protocells is based on the optimal metabolic yield of the protocells, which is computed using flux balance analysis.
The introduced computational model allows for profound investigations of the evolution of
early metabolism and the underlying evolutionary mechanisms. One application in this thesis
is the study of the formation of metabolic pathways. Therefore, four established hypothe-
ses, namely the backwards evolution, forward evolution, patchwork evolution and the shell
hypothesis, are discussed within the realms of this in silico evolution study. The metabolic
pathways of the networks, evolved in various simulation runs, are determined and analyzed
in terms of their evolutionary direction. The simulation results suggest that the seemingly
mutually exclusive hypotheses may well be compatible when considering that different pro-
cesses dominate different phases in the evolution of a metabolic system. Further, it is found
that forward evolution shapes the metabolic network in the very early steps of evolution. In
later and more complex stages, enzyme recruitment supersedes forward evolution, keeping a
core set of pathways from the early phase. Backward evolution can only be observed under
conditions of steady environmental change. Additionally, evolutionary history of enzymes
and metabolites were studied on the network level as well as for single instances, showing a
great variety of evolutionary mechanisms at work.
The second major focus of the in silico evolutionary study is the emergence of complex system
properties, such as robustness and modularity. To this end several techniques to analyze the
metabolic systems were used. The measures for complex properties stem from the fields of
graph theory, steady state analysis and neutral network theory. Some are used in general
network analysis and others were developed specifically for the purpose introduced in this
work. To discover potential sources for the emergence of system properties, three different
evolutionary scenarios were tested and compared. The first two scenarios are the same as
for the first part of the investigation, one scenario of evolution under static conditions and
one incorporating a steady change in the set of ”food” molecules. A third scenario was
added that also simulates a static evolution but with an increased mutation rate and regular
events of horizontal gene transfer between protocells of the population. The comparison of all
three scenarios with real world metabolic networks shows a significant similarity in structure
and properties. Among the three scenarios, the two static evolutions yield the most robust
metabolic networks, however, the networks evolved under environmental change exhibit their
own strategy to a robustness more suited to their conditions. As expected from theory,
horizontal gene transfer and changes in the environment seem to produce higher degrees
of modularity in metabolism. Both scenarios develop rather different kinds of modularity,
while horizontal gene transfer provides for more isolated modules, the modules of the second
scenario are far more interconnected
Independence and Accountability of Monetary and Fiscal Policy Committees
The democratic accountability of policymaking institutions which are autonomous within delegated mandates has not received as much attention as their independence. We analyze in a theoretical model the effects of accountability in the form of possible overriding of economic policy decisions by the government under different degrees of independence of expert committees conducting monetary and fiscal policy. The equilibrium outcomes of such alternative institution-design frameworks are compared according to key macroeconomic performance criteria. Our results stress the trade-off between anchoring inflation expectations on target and output stabilization that is not solved with accountability
A Sequence-to-Function Map for Ribozyme-catalyzed Metabolisms
We introduce a novel genotype-phenotype mapping based on
the relation between RNA sequence and its secondary structure for the
use in evolutionary studies. Various extensive studies concerning RNA
folding in the context of neutral theory yielded insights about properties of the structure space and the mapping itself. We intend to get a
better understanding of some of these properties and especially of the
evolution of RNA-molecules as well as their effect on the evolution of the
entire molecular system. We investigate the constitution of the neutral
network and compare our mapping with other artificial approaches using
cellular automatons, random boolean networks and others also based on
RNA folding. We yield the highest extent, connectivity and evolvability
of the underlying neutral network. Further, we successfully apply the
mapping in an existing model for the evolution of a ribozyme-catalyzed
metabolism
k-PathA: k-shortest Path Algorithm
One important aspect of computational systems biology
includes the identification and analysis of functional response
networks within large biochemical networks. These functional
response networks represent the response of a biological system
under a particular experimental condition which can be used to
pinpoint critical biological processes.
For this purpose, we have developed a novel algorithm to calculate
response networks as scored/weighted sub-graphs spanned by
k-shortest simple (loop free) paths. The k-shortest simple path
algorithm is based on a forward/backward chaining approach
synchronized between pairs of processors. The algorithm scales
linear with the number of processors used. The algorithm
implementation is using a Linux cluster platform, MPI lam
and mpiJava messaging as well as the Java language for the
application.
The algorithm is performed on a hybrid human network consisting
of 45,041 nodes and 438,567 interactions together with
gene expression information obtained from human cell-lines
infected by influenza virus. Its response networks show the early
innate immune response and virus triggered processes within
human epithelial cells. Especially under the imminent threat of
a pandemic caused by novel influenza strains, such as the current
H1N1 strain, these analyses are crucial for a comprehensive
understanding of molecular processes during early phases of
infection. Such a systems level understanding may aid in the
identification of therapeutic markers and in drug development
for diagnosis and finally prevention of a potentially dangerous
disease
Simulation tools for particle-based reaction-diffusion dynamics in continuous space
Particle-based reaction-diffusion algorithms facilitate the modeling of the diffusional motion of individual molecules and the reactions between them in cellular environments. A physically realistic model, depending on the system at hand and the questions asked, would require different levels of modeling detail such as particle diffusion, geometrical confinement, particle volume exclusion or particle-particle interaction potentials. Higher levels of detail usually correspond to increased number of parameters and higher computational cost. Certain systems however, require these investments to be modeled adequately. Here we present a review on the current field of particle-based reaction-diffusion software packages operating on continuous space. Four nested levels of modeling detail are identified that capture incrementing amount of detail. Their applicability to different biological questions is discussed, arching from straight diffusion simulations to sophisticated and expensive models that bridge towards coarse grained molecular dynamics
A real options approach for valuating intertemporal interdependencies within a value-based IT portfolio management - A risk-return perspective
Value-based IT portfolio management requires the consideration of intertemporal interdependencies that may exist among IT projects. Therefore, several papers suggest adopting the real options approach in order to include intertemporal interdependencies within the valuation of IT projects. However, this paper shows that the standard Black-Scholes model, which is often used for valuating real options, is not appropriate to correctly account for project-specific private risks due to its restrictive assumptions. Since this can have major impacts on the value of IT projects, we develop an approach – based on the Black-Scholes model – to consider private risks properly within project valuation. A comparison of the results of the standard Black-Scholes model used today and our approach finally reveals that the neglect of private risks results in a systematic underestimation of both risk and return of IT projects, which may lead to wrong investment decisions
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