Epigenetic information is encoded by DNA methylation and by covalent modifications of histone tails. While defined epigenetic modification patterns have been frequently correlated with particular states of gene activity, very little is known about the integration level of epigenetic signals. Recent experiments have resulted in the characterization of several epigenetic adaptors that mediate interactions between distinct modifications. These adaptors include methyl‐DNA binding proteins, chromatin remodelling enzymes and siRNAs. Complex interactions between epigenetic modifiers and adaptors provide the foundation for the stability (...) of epigenetic inheritance. In addition, they also provide an explanation for the long‐range effects of epigenetic mechanisms. We propose that a major aspect of epigenetic regulation lies in the modification of chromosome architecture and that local changes in gene expression would be secondary consequences. This view is consistent with many results from recent genomic analyses. BioEssays 25:792–797, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Recent studies have revealed an astonishing diversity of sex chromosomes in many vertebrate lineages, prompting questions about the mechanisms of sex chromosome turnover. While there is considerable population genetic theory about the evolutionary forces promoting sex chromosome replacement, this theory has not yet been integrated with our understanding of the molecular and developmental genetics of sex determination. Here, we review recent data to examine four questions about how the structure of gene networks influences the evolution of sex determination. (...) We argue that patterns of epistasis, arising from the structure of genetic networks, may play an important role in regulating the rates and patterns of sex chromosome replacement. (shrink)

How eukaryotic genomes are packaged into compact cylindrical chromosomes in preparation for cell divisions has remained one of the major unsolved questions of cell biology. Novel approaches to study the topology of DNA helices inside the nuclei of intact cells, paired with computational modeling and precise biomechanical measurements of isolated chromosomes, have advanced our understanding of mitotic chromosome architecture. In this Review Essay, we discuss – in light of these recent insights – the role of chromatin architecture (...) and the functions and possible mechanisms of SMC protein complexes and other molecular machines in the formation of mitotic chromosomes. Based on the information available, we propose a stepwise model of mitotic chromosome condensation that envisions the sequential generation of intra‐chromosomal linkages by condensin complexes in the context of cohesin‐mediated inter‐chromosomal linkages, assisted by topoisomerase II. The described scenario results in rod‐shaped metaphase chromosomes ready for their segregation to the cell poles. (shrink)

Chromosomes are not randomly packed and positioned into the nucleus but folded in higher‐order chromatin structures with defined functions. However, the genome of a fertilized embryo undergoes a dramatic epigenetic reprogramming characterized by extensive chromatin relaxation and the lack of a defined three‐dimensional structure. This reprogramming is followed by a slow genome refolding that gradually strengthens the chromatin architecture during preimplantation development. Interestingly, genome refolding during early development coincides with a progressive loss of developmental potential suggesting a link between (...) chromatin organization and cell plasticity. In agreement, loss of chromatin architecture upon depletion of the insulator transcription factor CTCF in embryonic stem cells led to the upregulation of the transcriptional program found in totipotent cells of the embryo, those with the highest developmental potential. This essay will discuss the impact of genome folding in controlling the expression of transcriptional programs involved in early development and their plastic‐associated features. (shrink)

Genome maintenance requires various nucleoid-associated factors in prokaryotes. Among them, the SMC protein has been thought to play a static role in the organization and segregation of the chromosome during cell division. However, recent studies have shown that the bacterial SMC is required to align left and right arms of the emerging chromosome and that the protein dynamically travels from origin to Ter region. A rod form of the SMC complex mediates DNA bridging and has been recognized as (...) a machinery responsible for DNA loop extrusion, like eukaryotic condensin or cohesin complexes, which act as chromosome organizers. Attention is now turning to how the prototype of the complex is loaded on the entry site and translocated on chromosomal DNA, explaining its overall conformational changes at atomic levels. Here, we review and highlight recent findings concerning the prokaryotic SMC complex and discuss possible mechanisms from the viewpoint of protein architecture. Recent studies show dynamic movements of the prokaryotic SMC protein complex: initial loading, translocation on DNA for bacterial chromosome organization. The recent structural models of the protein also provide a new vision for the structure-function relationship. (shrink)

The largest group of transcription factors in higher eukaryotes are C2H2 proteins, which contain C2H2‐type zinc finger domains that specifically bind to DNA. Few well‐studied C2H2 proteins, however, demonstrate their key role in the control of gene expression and chromosome architecture. Here we review the features of the domain architecture of C2H2 proteins and the likely origin of C2H2 zinc fingers. A comprehensive investigation of proteomes for the presence of proteins with multiple clustered C2H2 domains has revealed (...) a key difference between groups of organisms. Unlike plants, transcription factors in metazoans contain clusters of C2H2 domains typically separated by a linker with the TGEKP consensus sequence. The average size of C2H2 clusters varies substantially, even between genomes of higher metazoans, and with a tendency to increase in combination with SCAN, and especially KRAB domains, reflecting the increasing complexity of gene regulatory networks. (shrink)

Enzymatic misrepair of ionizing‐radiation‐induced DNA damage can produce large‐scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large‐scale chromatin architecture in the interphase nucleus. Most results are consistent with (...) a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage‐and‐reunion model, suggesting that the dominant recombinational mechanism during the G0/G1 phase of the cell cycle is non‐homologous end‐joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health‐related applications. BioEssays 24:714–723, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress (...) tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. PTEN is a guardian of the genome. However, the role of PTEN in guarding the genome has not been revealed until recently. PTEN controls multiple fundamental processes of genomic transmission. By physically interacting with key molecules in DNA replication, DNA repair/decatenation, and chromosome segregation during the cell cycle, PTEN maintains genomicintegrity and fitness. (shrink)

Three‐dimensional structured illumination microscopy (3D‐SIM) has opened up new possibilities to study nuclear architecture at the ultrastructural level down to the ∼100 nm range. We present first results and assess the potential using 3D‐SIM in combination with 3D fluorescence in situ hybridization (3D‐FISH) for the topographical analysis of defined nuclear targets. Our study also deals with the concern that artifacts produced by FISH may counteract the gain in resolution. We address the topography of DAPI‐stained DNA in nuclei before and (...) after 3D‐FISH, nuclear pores and the lamina, chromosome territories, chromatin domains, and individual gene loci. We also look at the replication patterns of chromocenters and the topographical relationship ofXist‐RNA within the inactive X‐territory. These examples demonstrate that an appropriately adapted 3D‐FISH/3D‐SIM approach preserves key characteristics of the nuclear ultrastructure and that the gain in information obtained by 3D‐SIM yields new insights into the functional nuclear organization. (shrink)

In this review, we focus on the evolutionary and biomedical aspects of the architecture of human chromosome 3 (HSA3) by analyzing chromosomal regions that have been conserved during the evolutionary process, compared to those that have been involved in the genomic restructuring of different placental lineages. Given that the organization of human chromosome 3 is derived when compared to the ancestral primate karyotype, and is an autosome that is commonly implicated in human tumour formation, we examined the (...) patterns of change and the genomic consequences that have resulted from its complex evolutionary history. The data show four discrete chromosomal regions that are frequently implicated in chromosomal rearrangements (3p25, 3p22, 3p12 and 3q21). These are rich in repetitive elements and are commonly implicated in structural rearrangements that underpin human genomic disorders and neoplasias. Additional Supporting Information may be found in the online version of this article. BioEssays 30:1126–1137, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Fluorescent in situ hybridization technology is one of the most exciting and versatile research tools to be developed in recent years. It has enabled research to progress at a phenomenal rate in diverse areas of basic research as well as in clinical medicine. Fluorescent in situ hybridization has applications in physical mapping, the study of nuclear architecture and chromatin packaging, and the investigation of fundamental principles of biology such as DNA replication, RNA processing, gene amplification, gene integration and chromatin (...) elimination. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field. (shrink)

Recent advances in genomic and imaging techniques have revealed the complex manner of organizing billions of base pairs of DNA necessary for maintaining their functionality and ensuring the proper expression of genetic information. The SMC proteins and cohesin complex primarily contribute to forming higher‐order chromatin structures, such as chromosomal territories, compartments, topologically associating domains (TADs) and chromatin loops anchored by CCCTC‐binding factor (CTCF) protein or other genome organizers. Cohesin plays a fundamental role in chromatin organization, gene expression and regulation. This (...) review aims to describe the current understanding of the dynamic nature of the cohesin‐DNA complex and its dependence on cohesin for genome maintenance. We discuss the current 3C technique and numerous bioinformatics pipelines used to comprehend structural genomics and epigenetics focusing on the analysis of Cohesin‐centred interactions. We also incorporate our present comprehension of Loop Extrusion (LE) and insights from stochastic modelling. (shrink)

Chromosomes are not only carriers of the genetic material, but also actively regulate the assembly of complex intracellular architectures. During mitosis, chromosome‐induced microtubule polymerisation ensures spindle assembly in cells without centrosomes and plays a supportive role in centrosome‐containing cells. Chromosomal signals also mediate post‐mitotic nuclear envelope (NE) re‐formation. Recent studies using novel approaches to manipulate histones in oocytes, where functions can be analysed in the absence of transcription, have established that nucleosomes, but not DNA alone, mediate the chromosomal regulation (...) of spindle assembly and NE formation. Both processes require the generation of RanGTP by RCC1 recruited to nucleosomes but nucleosomes also acquire cell cycle stage specific regulators, Aurora B in mitosis and ELYS, the initiator of nuclear pore complex assembly, at mitotic exit. Here, we review the mechanisms by which nucleosomes control assembly and functions of the spindle and the NE, and discuss their implications for genome maintenance. (shrink)

The three‐dimensional architecture of the bacterial chromosome is intertwined with genome processes such as transcription and replication. Conspicuously so, that the structure of the chromosome permits accurate prediction of active genome processes. Although appreciation of this interplay has developed rapidly in the past two decades, our understanding of this subject is still in its infancy, with research primarily focusing on how the process of transcription regulates and is regulated by chromosome structure. Here, we summarize the latest (...) developments in the field with a focus on the interplay between chromosome structure and transcription in Escherichia coli (E. coli) as mediated by H‐NS—a model nucleoid structuring protein. We describe how the organization of chromosomes at the global and local scales is dependent on transcription, and how transcription is regulated by chromosome structure. Finally, we take note of studies that highlight our limited knowledge of structure‐function relationships in the chromosome, and we point out research tracks that will improve our insight in the topic. (shrink)

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes (...) and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoletic development and phenotypic variation. BioEssays 25:930-939,2003. (C) 2003 Wiley Periodicals, Inc. (shrink)

Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three‐dimensional (3D) organization of genomes in the nucleus should be intrinsically linked to their biological functions. However, our understanding of the mechanisms underlying both the topological organization of genomes and the various nuclear processes is still largely (...) incomplete. In this essay, we focus on the functional relevance as well as the biophysical properties of common organizational themes in genomes (e.g. looping, clustering, compartmentalization, and dynamics), and examine the interconnection between genome structure and function from this angle. Present evidence supports the idea that, in general, genome architecture reflects and influences genome function, and is relatively stable. However, the answer as to whether genome architecture is a hallmark of cell identity remains elusive. (shrink)

Hameroff: I became interested in understanding consciousness as an undergraduate at the University of Pittsburgh in the late 60's. In my third year of medical school at Hahnemann in Philadelphia I did a research elective in professor Ben Kahn's hematology-oncology lab. They were studying various types of malignant blood cells, and I became interested in mitosis-looking under the microscope at normal and abnormal cell division. I became fascinated by centrioles and mitotic spindles pulling apart the chromosomes, doing this little dance, (...) dividing the cytoplasm, establishing the daughter-cell architecture, and beginning differentiation. I remember wondering to myself how these centrioles and mitotic spindles "knew" where to go and what to do. What kind of intelligence was running the show at the cellular level? (shrink)

Microtubules are protein cylinders with functions in cell motility, signal sensing, cell organization, intracellular transport, and chromosome segregation. One of the key properties of microtubules is their dynamic architecture, allowing them to grow and shrink in length by adding or removing copies of their basic subunit, the heterodimer αβ‐tubulin. In higher eukaryotes, de novo assembly of microtubules from αβ‐tubulin is initiated by a 2 MDa multi‐subunit complex, the gamma‐tubulin ring complex (γ‐TuRC). For many years, the structure of the (...) γ‐TuRC and the function of its subunits remained enigmatic, although structural data from the much simpler yeast counterpart, the γ‐tubulin small complex (γ‐TuSC), were available. Two recent breakthroughs in the field, high‐resolution structural analysis and recombinant reconstitution of the complex, have revolutionized our knowledge about the architecture and function of the γ‐TuRC and will form the basis for addressing outstanding questions about biogenesis and regulation of this essential microtubule organizer. (shrink)

t is now well accepted that defined architectural compartments within the cell nucleus can regulate the transcriptional activity of chromosomal domains within their vicinity. However, it is generally unclear how these compartments are formed. The nuclear periphery has received a great deal of attention as a repressive compartment that is implicated in many cellular functions during development and disease. The inner nuclear membrane, the nuclear lamina, and associated proteins compose the nuclear periphery and together they interact with proximal chromatin creating (...) a repressive environment. A new study by Harr et al. identifies specific protein–DNA interactions and epigenetic states necessary to re‐position chromatin to the nuclear periphery in a cell‐type specific manner. Here, we review concepts in gene positioning within the nucleus and current accepted models of dynamic gene repositioning within the nucleus during differentiation. This study highlights that myriad pathways lead to nuclear organization. (shrink)

Somatic mutation plays a key role in transforming normal cells into cancerous cells. The analysis of cancer progression therefore requires the study of how point mutations and chromosomal mutations accumulate in cellular lineages. The spread of somatic mutations depends on the mutation rate, the number of cell divisions in the history of a cellular lineage, and the nature of competition between different cellular lineages. We consider how various aspects of tissue architecture and cellular competition affect the pace of mutation (...) accumulation. We also discuss the rise and fall of somatic mutation rates during cancer progression. BioEssays 26:291–299, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Sister chromatid separation in anaphase is an important event in the cell's transmission of genetic information to a descendent. It has been investigated from different aspects: cell cycle regulation, spindle and chromosome dynamics within the three‐dimensional cell architecture, transmission fidelity control and cellular signaling. Integrated studies directed toward unified understanding are possible using multidisciplinary methods with model organisms. Ubiquitin‐dependent proteolysis, protein dephosphorylation, an unknown function by the TPR repeat proteins, chromosome transport by microtubule‐based motors and DNA topological (...) change by DNA topoisomerase II are all necessary for progression from metaphase to anaphase. Chromosome condensation, mitotic kinetochore function and spindle formation require a large number of proteins, which are prerequisites for successful sister chromatid separation. Factors that help to retain sister chromatid connection after replication and prevent premature separation remain to be determined. Although sister chromatid separation occurs in anaphase, gene functions in other cell cycle stages also ensure the progression of correct chromatid separation. (shrink)

Cohesion is established in S‐phase through the action of key replisome factors as replication forks engage cohesin molecules. By holding sister chromatids together, cohesion critically assists both an equal segregation of the duplicated genetic material and an efficient repair of DNA breaks. Nonetheless, the molecular events leading the entrapment of nascent chromatids by cohesin during replication are only beginning to be understood. The authors describe here the essential structural features of the cohesin complex in connection to its ability to associate (...) DNA molecules and review the current knowledge on the architectural‐functional organization of the eukaryotic replisome, significantly advanced by recent biochemical and structural studies. In light of this novel insight, the authors discuss the mechanisms proposed to assist interfacing of replisomes with chromatin‐bound cohesin complexes and elaborate on models for nascent chromatids entrapment by cohesin in the environment of the replication fork. (shrink)

Within the last decade, the study of mitosis has evolved into a multidisciplinary science in which findings from fields as diverse as chromosome biology and cytoskeletal architecture have converged to present a more cohesive understanding of the complex events that occur when cells divide. The largest strides have been made in the identification and characterization of regulatory enzymes (kinases and phosphatases) that modulate mitotic activity, as well as a number of the proteins and structural components (spindle, chromosomes, nuclear (...) envelope) which carry out the mitotic instructions. One emerging theme appears to be that molecular signalling, which can involve modification of components (such as phosphorylation) or even their specific destruction, monitors the state of the mitotic cell at all stages. One of the major challenges for the future will be the identification of addititonal targets of the signalling machinery, as well as new regulatory components and their targets on the chromosomes, on the spindle, and at the cleavage furrow. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information (...) that underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

The genetic stability of living cells is continuously threatened by the presence of endogenous reactive oxygen species and other genotoxic molecules. Of particular threat are the thousands of DNA single-strand breaks that arise in each cell, each day, both directly from disintegration of damaged sugars and indirectly from the excision repair of damaged bases. If un-repaired, single-strand breaks can be converted into double-strand breaks during DNA replication, potentially resulting in chromosomal rearrangement and genetic deletion. Consequently, cells have adopted multiple pathways (...) to ensure the rapid and efficient removal of single-strand breaks. A general feature of these pathways appears to be the extensive employment of protein–protein interactions to stimulate both the individual component steps and the overall repair reaction. Our current understanding of DNA single-strand break repair is discussed, and testable models for the architectural coordination of this important process are presented. BioEssays 23:447–455, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The model provided by the organismic point of view is quite different. Without having recourse to any transcendent vital force or immanent teleology, it nevertheless rejects the basic ideas of mechanism. More specifically, it replaces the analytical- summative conception by the idea of biological organisms as wholes or systems which have unique system-properties and obey irreducible system-laws. The machine-theoretical conception is replaced by a dynamic interpretation of living things, wherein organic structures are due to a continuous flow of processes combining (...) to produce patterns of immense intricacy. The reaction-theoretical conception is jettisoned in favour of the view that the organism is primarily a center of activity which is autonomous and not a mere response to external stimuli. Finally, the organismic model considers that biological systems are stratified, so that, e.g., viruses, genes, chromosomes, cells, multicellular individuals, supra-individual aggregates, etc., form a hierarchy of "levels" exhibiting an increasing degree of complexity. The whole of nature, indeed, contains "a tremendous architecture, in which subordinate systems are united at successive levels into ever higher and larger systems.". (shrink)

Volume 23, Issue 2, April 2024, Page 187-223.

This paper explores the difference between Connectionist proposals for cognitive a r c h i t e c t u r e a n d t h e s o r t s o f m o d e l s t hat have traditionally been assum e d i n c o g n i t i v e s c i e n c e . W e c l a i m t h a t t h (...) e m a j o r d i s t i n c t i o n i s t h a t , w h i l e b o t h Connectionist and Classical architectures postulate representational mental states, the latter but not the former are committed to a symbol-level of representation, or to a ‘language of thought’: i.e., to representational states that have combinatorial syntactic and semantic structure. Several arguments for combinatorial structure in mental representations are then reviewed. These include arguments based on the ‘systematicity’ of mental representation: i.e., on the fact that cognitive capacities always exhibit certain symmetries, so that the ability to entertain a given thought implies the ability to entertain thoughts with semantically related contents. We claim that such arguments make a powerful case that mind/brain architecture is not Connectionist at the cognitive level. We then consider the possibility that Connectionism may provide an account of the neural (or ‘abstract neurological’) structures in which Classical cognitive architecture is implemented. We survey a n u m b e r o f t h e s t a n d a r d a r g u m e n t s t h a t h a v e b e e n o f f e r e d i n f a v o r o f Connectionism, and conclude that they are coherent only on this interpretation. (shrink)

Scholars have paid ample attention to Aristotle's works on animals. By contrast, they have paid little or no attention to Theophrastus' writings on plants. That is unfortunate because there was a shared research project in the early Peripatos which amounted to a systematic, and theoretically motivated, study of perishable living beings (animals and plants). This is the first sustained attempt to explore how Aristotle and Theophrastus envisioned this study, with attention focused primarily on its deep structure. That entails giving full (...) consideration to a few transitional passages where Aristotle and Theophrastus offer their own description of what they are trying to do. What emerges is a novel, sophisticated, and largely idiosyncratic approach to the topic of life. This title is also available as Open Access on Cambridge Core. (shrink)

This essay explores a conception of responsibility at work in moral and criminal responsibility. Our conception draws on work in the compatibilist tradition that focuses on the choices of agents who are reasons-responsive and work in criminal jurisprudence that understands responsibility in terms of the choices of agents who have capacities for practical reason and whose situation affords them the fair opportunity to avoid wrongdoing. Our conception brings together the dimensions of normative competence and situational control, and we factor normative (...) competence into cognitive and volitional capacities, which we treat as equally important to normative competence and responsibility. Normative competence and situational control can and should be understood as expressing a common concern that blame and punishment presuppose that the agent had a fair opportunity to avoid wrongdoing. This fair opportunity is the umbrella concept in our understanding of responsibility, one that explains it distinctive architecture. (shrink)

헤겔에 의하면 상징적 예술형식이 건축의 근본전형이지만, 건축은 그 내부에서 다시 상징적 건축, 고전적 건축, 낭만적 건축으로 구분된다. 이 점에서 낭만적 건축을 대표하는 고딕 건축이 어떤 예술형식에 속하는지가 문제될 수 있다. 헤겔은 괴테의 건축론을 수용하면서 고딕 건축이 중세에만 한정되지 않고 그 당대의 건축까지 포괄한다고 생각한다. 고딕 건축이 보여주는 특징은 대립하는 요소들의 공존을 공간적으로 구현함으로써, 인간 정신의 내면성을 강화하면서 유한성을 뛰어 넘을 수 있게 한다는 점이다. 더 나아가 고딕 건축은 살아있는 인간의 다양한 일상이 발생하는 장소이기도 한데, 이를 표현하기 위해 헤겔은 ‘노마드’라는 개념을 (...) 사용하기도 한다. 이러한 점들을 고려하면 고딕건축은 낭만적 예술로 간주되어야 적절할 뿐만 아니라 ‘세상의 축소판’으로 해석될 수도 있다. 이처럼 고딕 건축에 관한 헤겔의 논의는 근대 소설이나 후기 네덜란드 장르화에 관한 그의 논의에 버금갈 정도로 근대적 삶에 대한 예술비평으로 간주될 수 있으므로, 헤겔의 건축론은 다른 예술론에 비해 과소 평가되어서는 안 된다. (shrink)

The literature on theoretical reason has been dominated by epistemological concerns, treatments of practical reason by ethical concerns. This book overcomes the limitations of dealing with each separately. It sets out a comprehensive theory of rationality applicable to both practical and theoretical reason. In both domains, Audi explains how experience grounds rationality, delineates the structure of central elements, and attacks the egocentric conception of rationality. He establishes the rationality of altruism and thereby supports major moral principles. The concluding part describes (...) the pluralism and relativity his conception of rationality accommodates and, taking the unified account of theoretical and practical rationality in that light, constructs a theory of global rationality--the overall rationality of persons. Rich in narrative examples, intriguing analogies, and intuitively appealing arguments, this beautifully crafted book will spur advances in ethics and epistemology as well in philosophy of mind and action and the theory of rationality itself. (shrink)

In this paper we compare two theories about the cognitive architecture underlying morality. One theory, proposed by Sripada and Stich (forthcoming), posits an interlocking set of innate mechanisms that internalize moral norms from the surrounding community and generate intrinsic motivation to comply with these norms and to punish violators. The other theory, which we call the M/C model was suggested by the widely discussed and influential work of Elliott Turiel, Larry Nucci and others on the “moral/conventional task”. This theory (...) posits two distinct mental domains, the moral and the conventional, each of which gives rise to a characteristic suite of judgments about rules in that domain and about transgressions of those rules. We give an overview of both theories and of the data each was designed to explain. We go on to consider a growing body of evidence that suggests the M/C model is mistaken. That same evidence, however, is consistent with the Sripada and Stich theory. Thus, we conclude that the M/C model does not pose a serious challenge for the Sripada and Stich theory. (shrink)

This volume provides the reader with an integrated overview of state-of-the-art research in philosophy and ethics of design in engineering and architecture.

The concept of “Bio-Digital Architecture” is not new and it is within an area of great speculation and few well-demarcated definitions. A key factor in the definition and practice of technology is the difference between its production and use. If we assume that forms of use are also technical, this distinction is intrinsic to countries based on economies without added value and their histories focused on reverting this situation. This article proposes the revision of a paradigm shift in South (...) America that combined the sustainable “Bio Architecture” background from the developmental state with a different economic model era. Through a historical review of the sociology of symbolic production, and the development of devices and interfaces, mechanisms are proposed to recognize paradigm shifts, in a context where technological utopias are associated with the materialization of new social utopias of developing. Focused on specific cases, this research explains the culmination of the principles of “Second-order cybernetics”, in the epistemological formulation of “Autopiesis”, and the early visualization of these principles through digital media in the experience of “Protobio”. Finally, this work concludes with the description of the concrete application of these principles, not in an illustrative way, but in the design of the electronic information architecture of the operating system, continuing with the challenge of translating the logic of the immune system into an economic, political and social context completely different from its predecessors, with “Virus Detection”—VirDet—and “Oyster 2.0”. (shrink)

In recent years, the distributed architecture has been widely adopted by security companies with the rapid expansion of their business. A distributed system is comprised of many computing nodes of different components which are connected by high-speed communication networks. With the increasing functionality and complexity of the systems, failures of nodes are inevitable which may result in considerable loss. In order to identify anomalies of the possible failures and enable DevOps engineers to operate in advance, this paper proposes a (...) two-layer prediction architecture based on the monitoring sequences of nodes status. Generally speaking, in the first layer, we make use of EXPoSE anomaly detection technique to derive anomaly scores in constant time which are then used as input data for ensemble learning in the second layer. Experiments are conducted on the data provided by one of the largest security companies, and the results demonstrate the predictability of the proposed approach. (shrink)

The representational nature of human cognition and thought in general has been a source of controversies. This is particularly so in the context of studies of unconscious cognition, in which representations tend to be ontologically and structurally segregated with regard to their conscious status. However, it appears evolutionarily and developmentally unwarranted to posit such segregations, as,otherwise, artifact structures and ontologies must be concocted to explain them from the viewpoint of the human cognitive architecture. Here, from a by-and-large Classical cognitivist (...) viewpoint, I show why this segregation is wrong, and elaborate on the need to postulate an ontological and structural continuity between unconscious and conscious representations. Specifically, I hypothesize that this continuity is to be found in the symbolic-based interplay between the syntax and the semantics of thought, and I propose a model of human information processing characterized by the integration of syntactic and semantic representations. (shrink)

William Whewell’s work on historical science has received some attention from historians and philosophers of science. Whewell’s own work on the history of German Gothic church architecture has been touched on within the context of the history of architecture. To a large extent these discussions have been conducted separately. I argue that Whewell intended his work on Gothic architecture as an attempt to (help) found a science of historical architecture, as an exemplar of historical science. I (...) proceed by analyzing the key features of Whewell’s philosophy of historical science. I then show how his architectural history exemplifies this philosophy. Finally, I show how Whewell’s philosophy of historical science matches some developments in a science (biological systematics) that, in the mid-to latenineteenth century, came to be reinterpreted as a historical science. I comment briefly on Whewell as a potential influence on nineteenth century biology and in particular on Darwin. (shrink)

The past four decades of research in the social sciences have shed light on two important phenomena. One is that human decision-making is full of predicable errors and biases that often lead individuals to make choices that defeat their own ends (i.e., the bad choice phenomenon), and the other is that individuals’ decisions and behaviors are powerfully shaped by their environment (i.e., the influence phenomenon). Some have argued that it is ethically defensible that the influence phenomenon be utilized to address (...) the bad choice phenomenon. They propose that “choice architects” learn about the various ways in which choices can be influenced and directed by the environment, and then work to design environments, broadly construed, that influence individuals towards choices that make them better off. Those who advocate intentionally creating choice environments that lead people to better choices believe that doing so is ethically permissible because (1) it makes people better off, and (2) it does so in a way that is entirely compatible with individual liberty. The evaluation of these two claims is the main focus of this paper. (shrink)

Bateson's belated acceptance of the chromosome theory came in two main stages, and was permanent, although he retained to the end reservations about some implications and extensions of the theory. Coleman's attempt to explain Bateson's resistance in terms of his conservative mode of thought is critically examined, and rejected: the attributes Coleman assigns to Bateson are all either inappropriate, or irrelevant to chromosome theory, or both. Instead, the diverse factors which contributed to Bateson's resistance are enumerated and discussed. (...) These include deficiencies in the evidence then available to support the theory; embryological difficulties; Bateson's aversion to microscopy combined with the lack of a close colleague skilled in cytology; his iconoclastic temperament, and the fact that he found T. H. Morgan, the leader of the Drosophila school, an uncongenial personality. Taken together, these factors suffice to account for his resistance. Bateson's position is contrasted with that of the other most eminent opponent, W. Johannsen, whose organismic outlook was the main obstacle to acceptance. (shrink)