1,978 research outputs found
Integrative Systems Toxicology for Human Health
No full textWesterhoff, H.V. [Promotor]Schuhmacher, M. [Promotor]Kolodkin, A.N. [Copromotor]Kumar, V. [Copromotor
Musikstädte as real and imaginary soundscapes: urban musical images as literary motifs in twentieth-century German modernism
No full textPhDThis study examines German literary images of musical life as part of the wider sound identity of the modern German city at the turn of the twentieth century. Focussing on a forty-year period from 1890 to 1930, synonymous with the emergence of the modern German metropolis as an aesthetic object, the project assesses, compares and contrasts how musical life in the Musikstädte was perceived and portrayed by writers in an increasingly noisy urban environment. How does urban musical life influence and condition city writings? What are the differences and similarities between the writings on various musical cities? Can an urban textual sound identity be derived from these differences and similarities? The approach employed to answer these questions is a new, cross-disciplinary one to urban sound in literature, moving beyond reading the key sounds of the urban soundscape using urban musicology, sensorial anthropology and cultural poetics towards a literary contextualisation of the urban aural experience.
The literary motifs of the symphony, the gramophone and urban noise are put under the spotlight through the analysis of a wide range of modernist works by authors who have a special relationship with music. At the centre of this analysis are the Kaffeehausliteratur authors Hermann Bahr, Alfred Polgar and Peter Altenberg, the then Munich-based author Thomas Mann and the lesser known René Schickele. The analysis of these particular works is framed in the music-geographical context of the Musikstadt and literary underpinnings of this topos, ranging from Ingeborg Bachmann to Hans Mayer and, once again, Thomas Mann. In analysing these texts, the methodological approach devised by Strohm, who identifies the blending of a range of urban sounds as a definition of urban space and identity, is applied. His ideas combine historical literary
analysis, musical history and urban sociology. They are rarely used in the analysis of the auditory environment.Arts and Humanities Research Council
Westfield TrustWestfield Trust Studentship
Arts and Humanities Reseach Council (AHRC
Data without models merging with models without data
No full textKrohs U, Callebaut W. Data without models merging with models without data. In: Boogerd FC, Bruggeman FJ, Hofmeyr J-HS, Westerhoff HV, eds. Systems Biology: Philosophical Foundations. Amsterdam [u.a.]: Elsevier; 2007: 181-213
(Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis
No full textBackground: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. [br/]
Results: This study integrates control engineering and classical MCA augmented with supply-demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the 'integral control' (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of 'integral control' should rarely be expected to lead to the 'perfect adaptation': although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. [br/]
Conclusions: A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems biology, correspond to the 'perfect' regulatory structures designed by control engineering vis-a-vis optimal functions such as robustness. To the extent that they are not, the analyses suggest how they may become so and this in turn should facilitate synthetic biology and metabolic engineering
On paradoxes between optimal growth, metabolic control analysis, and flux balance analysis
No full textIn Microbiology it is often assumed that growth rate is maximal. This may be taken to suggest that the dependence of the growth rate on every enzyme activity is at the top of an inverse-parabolic function, i.e. that all flux control coefficients should equal zero. This might seem to imply that the sum of these flux control coefficients equals zero. According to the summation law of Metabolic Control Analysis (MCA) the sum of flux control coefficients should equal 1 however. And in Flux Balance Analysis (FBA) catabolism is often limited by a hard bound, causing catabolism to fully control the fluxes, again in apparent contrast with a flux control coefficient of zero. Here we resolve these paradoxes (apparent contradictions) in an analysis that uses the ‘Edinburgh pathway’, the ‘Amsterdam pathway’, as well as a generic metabolic network providing the building blocks or Gibbs energy for microbial growth. We review and show that (i) optimization depends on so-called enzyme control coefficients rather than the ‘catalytic control coefficients’ of MCA's summation law, (ii) when optimization occurs at fixed total protein, the former differ from the latter to the extent that they may all become equal to zero in the optimum state, (iii) in more realistic scenarios of optimization where catalytically inert biomass is compensating or maintenance metabolism is taken into consideration, the optimum enzyme concentrations should not be expected to equal those that maximize the specific growth rate, (iv) optimization may be in terms of yield rather than specific growth rate, which resolves the paradox because the sum of catalytic control coefficients on yield equals 0, (v) FBA effectively maximizes growth yield, and for yield the summation law states 0 rather than 1, thereby removing the paradox, (vi) furthermore, FBA then comes more often to a ‘hard optimum’ defined by a maximum catabolic flux and a catabolic-enzyme control coefficient of 1. The trade-off between maintenance metabolism and growth is highlighted as worthy of further analysis.</p
ENZYME KINETICS FOR SYSTEMS BIOLOGY:WHEN, WHY AND HOW
No full textIn vitro enzymatic assays of cell-free extracts offer an opportunity to assess in vivo enzyme concentrations. If performed under conditions that resemble the conditions in vivo, they may also reveal some of the capacities and properties of the same enzymes in vivo; we shall call this the ex vivo approach. The kinetic characterization of purified enzymes has yet a different utility for systems biology, as does the in vivo determination of enzyme activities. All these approaches are different, and it is becoming important that the appropriate approach be used for the intended purpose. Here, we therefore discuss five approaches to the measurement of enzyme activity in terms of the source of the enzyme activity, the identity of the assay medium, and the purpose of the assay.</p
Modeling the E. coli cell: The need for computing, cooperation, and consortia
No full textEscherichia coli K-12 is an ideal test bed for pushing forward the limits of our
ability to understand cellular systems through computational modeling. A complete
understanding will require arrays of mathematical models, a wealth of data
from measurements of various life processes, and readily accessible databases that
can be interrogated for testing our understanding. Accomplishing this will require
improved approaches for mathematical modeling, unprecedented standardization
for experimentation and data collection, completeness of data sets, and improved
methods of accessing and linking information. Solving the whole cell problem,
even for a simple E. coli model cell, will require the concerted efforts of many
scientists with different expertise. In this chapter, we review advances in (i) computing
for modeling cells, (ii) creating a common language for representing computational
models (the Systems Biology Markup Language), and (iii) developing
the International E. coli Alliance, which has been created to tackle the whole cell
problem
Summation Laws in Control of Biochemical Systems
No full textDynamic variables in the non-equilibrium systems of life are determined by catalytic activities. These relate to the expression of the genome. The extent to which such a variable depends on the catalytic activity defined by a gene has become more and more important in view of the possibilities to modulate gene expression or intervene with enzyme function through the use of medicinal drugs. With all the complexity of cellular systems biology, there are still some very simple principles that guide the control of variables such as fluxes, concentrations, and half-times. Using time-unit invariance we here derive a multitude of laws governing the sums of the control coefficients that quantify the control of multiple variables by all the catalytic activities. We show that the sum of the control coefficients of any dynamic variable over all catalytic activities is determined by the control of the same property by time. When the variable is at a maximum, minimum or steady, this limits the sums to simple integers, such as 0, −1, 1, and −2, depending on the variable under consideration. Some of the implications for biological control are discussed as is the dependence of these results on the precise definition of control
Prosecutor v Hans Åkerberg Fransson (Case C-617/10), ECLI:EU:C:2013:105, [2013] 2 CMLR 46, 26 February 2013
No full textEssential Cases: EU Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Prosecutor v Hans Åkerberg Fransson (Case C-617/10), ECLI:EU:C:2013:105, [2013] 2 CMLR 46, 26 February 2013. The document also included supporting commentary from author Noreen O’Meara.</p
Introduction: Composition, Text, and Editing zu: James Joyce: A portrait of the artist as a young man
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