PDF version This talk explores three concepts of system in engineering: systems theory, systems approach, and systems engineering. They are exemplified in three dimensions of engineering: science, design, and management. Unifying the three system concepts is the idea of function: functional abstraction in theory, functional analysis in design, and functional requirements in management. Signifying what a system is for, function is a purposive notion absent in physical science, which aims to understand nature. It is prominent in engineering, which aims to (...) transform nature for serving the wants and needs of people. (shrink)

Several key areas in modeling the cardiovascular and respiratory control systems are reviewed and examples are given which reflect the research state of the art in these areas. Attention is given to the interrelated issues of data collection, experimental design, and model application including model development and analysis. Examples are given of current clinical problems which can be examined via modeling, and important issues related to model adaptation to the clinical setting.

Possible effects of interaction (cross-talk) between signaling pathways is studied in a system of Reaction–Diffusion (RD) equations. Furthermore, the relevance of spontaneous neurite symmetry breaking and Turing instability has been examined through numerical simulations. The interaction between Retinoic Acid (RA) and Notch signaling pathways is considered as a perturbation to RD system of axon-forming potential for N2a neuroblastoma cells. The present work suggests that large increases to the level of RA–Notch interaction can possibly have substantial impacts on neurite outgrowth and (...) on the process of axon formation. This can be observed by the numerical study of the homogeneous system showing that in the absence of RA–Notch interaction the unperturbed homogeneous system may exhibit different saddle-node bifurcations that are robust under small perturbations by low levels of RA–Notch interactions, while large increases in the level of RA–Notch interaction result in a number of transitions of saddle-node bifurcations into Hopf bifurcations. It is speculated that near a Hopf bifurcation, the regulations between the positive and negative feedbacks change in such a way that spontaneous symmetry breaking takes place only when transport of activated Notch protein takes place at a faster rate. (shrink)

Recently improved understanding of evolutionary processes suggests that tree-based phylogenetic analyses of evolutionary change cannot adequately explain the divergent evolutionary histories of a great many genes and gene complexes. In particular, genetic diversity in the genomes of prokaryotes, phages, and plasmids cannot be fit into classic tree-like models of evolution. These findings entail the need for fundamental reform of our understanding of molecular evolution and the need to devise alternative apparatus for integrated analysis of these genomes. We advocate the development (...) of integrative phylogenomics for analyzing these genomes and their histories, with tools suited to analyzing the importance of lateral gene transfer (LGT) and of DNA evolution in extra-cellular mobile genetic elements (e.g., viruses, plasmids). These phenomena greatly increase the complexity of relationships among interacting genetic partners, as they exchange functional genetic units. We examine the ontology of functional genetic units, interacting genetic partners, and emergent genetic associations, argue that these three categories of entities are required for a successful integrated phylogenomics. We conclude with arguments to suggest that the proposed new perspective and associated tools are suitable, and perhaps required, as a replacement for the bifurcating trees that have dominated evolutionary thinking for the last 150 years. (shrink)

Standard microbial evolutionary ontology is organized according to a nested hierarchy of entities at various levels of biological organization. It typically detects and defines these entities in relation to the most stable aspects of evolutionary processes, by identifying lineages evolving by a process of vertical inheritance from an ancestral entity. However, recent advances in microbiology indicate that such an ontology has important limitations. The various dynamics detected within microbiological systems reveal that a focus on the most stable entities (or features (...) of entities) over time inevitably underestimates the extent and nature of microbial diversity. These dynamics are not the outcome of the process of vertical descent alone. Other processes, often involving causal interactions between entities from distinct levels of biological organisation, or operating at different time scales, are responsible not only for the destabilisation of pre-existing entities, but also for the emergence and stabilisation of novel entities in the microbial world. In this article we consider microbial entities as more or less stabilised functional wholes, and sketch a network-based ontology that can represent a diverse set of processes including, for example, as well as phylogenetic relations, interactions that stabilise or destabilise the interacting entities, spatial relations, ecological connections, and genetic exchanges. We use this pluralistic framework for evaluating (i) the existing ontological assumptions in evolution (e.g. whether currently recognized entities are adequate for understanding the causes of change and stabilisation in the microbial world), and (ii) for identifying hidden ontological kinds, essentially invisible from within a more limited perspective. We propose to recognize additional classes of entities that provide new insights into the structure of the microbial world, namely “processually equivalent” entities, “processually versatile” entities, and “stabilized” entities. (shrink)

The levels that compose biological hierarchies each have their own energetic, spatial and temporal structure. Indeed, it is the discontinuity in energy relationships between levels, as well as the similarity of sub-systems that support them, that permits levels to be defined. In this paper, the temporal structure of living hierarchies, in particular that pertaining to Human society, is examined. Consideration is given to the period defining the lifespan of entities at each level and to a periodic event considered fundamental to (...) the maintenance of that level. The ratio between the duration of these two periods is found to be approximately 2.5 × 104. A similar relationship is found when lower, non-living levels of molecules and atoms are considered. This suggests that there is a constant factor of amplification between analogous periodic events at successive levels of the Human hierarchy. (shrink)

Richard Dawkins has popularized an argument which, according to him, proves that there is almost certainly no God. It rests on the assumption that complex and statistically improbable things are more difficult to explain than those that are not, and that any explanatory mechanism that is called on to do the explaining must show how this complexity can be built up from simpler means as it would be useless otherwise. In this paper, I first question what justifies the consideration of (...) the designer’s own complexity. I suggest a different understanding of both order and simplicity inevitable when one considers the psychological counterpart of information. I then assess what seems to be the inference engine of the proposal, the metaphor of biological organisms as either self-programmed machines or algorithms. I show how self-generated organized complexity would not sit well with our knowledge of both abduction and the theorems of information theory applied to genetics. I then turn to the positive side of Dawkins’ challenge, and I review some philosophers and their proposals for how the complexity of the world could be controlled from outside if one wanted to uphold a traditional understanding of God’s simplicity. (shrink)

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into (...) two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (shrink)

In this thesis I examine a number of topics that bear on explanation and understanding in molecular and cell biology, in order to shed new light on explanatory practice in those areas and to find novel angles from which to approach relevant philosophical debates. The topics I look at include mechanism, emergence, cellular complexity, and the informational role of the genome. I develop a perspective that stresses the intimacy of the relations between ontology and epistemology. Whether a phenomenon looks mechanistic, (...) or complex, or indeed emergent, is largely an epistemic matter, yet has an objective basis in features of the world. After reviewing several concepts of mechanism I consider the influential recent account of Machamer, Darden and Craver (MDC). That account makes interesting proposals concerning the relationship between mechanistic explanation and intelligibility, which are consistent with the results of the investigation I undertake into the science surrounding protein folding. In relation to a number of other issues pertaining to biological systems I conclude that the MDC account is insufficiently nuanced, however, leading me to outline an alternative approach to mechanism. This emphasizes the importance of structure—function relations and addresses issues raised by reflection on the nature of cellular complexity. These include the distinction between structure and process and the different possible bases on which system organization may be maintained. The account I give of emergence construes the phenomenon in terms of psychological deficit: phenomena are emergent when we lack the capacity to trace through and model their causal structures using our cognitive schemas. I conclude by developing these ideas into a preliminary and partial account of explanation and understanding. This aspires to cover the significant fraction of work in molecular and cell biology that correlates biological structures, processes and functions by visualizing phenomena and making them imaginable. (shrink)

My paper draws on examples from molecular biology, the details of which I have developed elsewhere (Rheinberger 1992, 1993, 1995, 1997). Here, I can give only a brief outline of my argument. Reduction of complexity is a prerequisite for experimental research. To make sense of the universe of living beings, the modern biologist is bound to divide his world into fragments in which parameters can be defined, quantities measured, qualities identified. Such is the nature of any "experimental system." Ontic complexity (...) has to be reduced in order to make experimental research possible. The complexity of the research object, however, is epistemically retained in the rich context of an experimental landscape, where the eruption of "volcanic systems" can change the scenery dramatically as the result of particular, unprecedented findings. (shrink)

The idea that the immune system distinguishes between self and non-self was one of the central assumptions of immunology in the second half of 20th century. This idea influenced experimental design and data interpretation. However, in the face of new evidence there is a need for a new conceptual framework in immunology.

Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how these stimuli (...) influence the course of immune activation. (shrink)