The expression of products encoded by the major histocompatibility complex (MHC) on tumor cells has recently been studied extensively. It has been found that many malignant tumor cells have their MHC antigens ‘switched‐off’ but that these antigens are re‐expressed following DNA‐mediated gene transfer, with increased tumor immunogenicity as a result and the consequence that these ‘transformed’ tumor cells are rejected in vivo.: This review will discuss approaches that have been taken to induce strong tumor‐specific immunity by the (...) manipulation of MHC expression on tumor cells. (shrink)

The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This ∼4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class II molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence (...) of novel genes. Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)‐light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue‐specific genes are localised predominantly in G‐light bands. (shrink)

Major histocompatibility complex (MHC)‐associated mate choice is thought to give offspring a fitness advantage through disease resistance. Primates offer a unique opportunity to understand MHC‐associated mate choice within our own zoological order, while their social diversity provides an exceptional setting to examine the genetic determinants and consequences of mate choice in animal societies. Although mate choice is constrained by social context, increasing evidence shows that MHC‐dependent mate choice occurs across the order in a variety of socio‐sexual systems (...) and favours mates with dissimilar, diverse or specific genotypes non‐exclusively. Recent research has also identified phenotypic indicators of MHC quality. Moreover, novel findings rehabilitate the importance of olfactory cues in signalling MHC genes and influencing primate mating decisions. These findings underline the importance to females of selecting a sexual partner of high genetic quality, as well as the generality of the role of MHC genes in sexual selection. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne’s later hypothesis (1971, European Journal of Immunology 1: 1–9), (...) that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187–198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC‐dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American (...) samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC‐dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC‐dependent mate choice in some human populations. (shrink)

Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll‐like (...) receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T‐ and B‐lymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS‐CoV‐2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID‐19 vaccinations could launch a new era of personalized healthcare. (shrink)

The T lymphocyte receptor for antigen, which operates in conjunction with gene products of the major histocompatibility complex (MHC), is a molecular complex comprised of five polypeptide chains. Both the 49 kDa alpha and 43 kDa beta chains are immunoglobulin‐like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25 kDa T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to (...) each other and held in noncovalent association with the T3 chains. T3‐Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50 kDa T11 structure which in turn leads to protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation. (shrink)

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to (...) the divergence of C3 and C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level. (shrink)

The molecular components of complement are a major part of the armoury of the mammalian immune system, being required for the lysis of antibody‐targeted cells. Several of the complement proteins are known to be encoded by genes within the major histocompatibility complex (MHC). Molecular analysis of these genes is providing new information on the basis of complement action and the possible roles of this system in autoimmune disease.

Soma‐to‐germline feedback is forbidden under the neo‐Darwinian paradigm. Nevertheless, there is a growing realization it occurs frequently in immunoglobulin (Ig) variable (V) region genes. This is a surprising development. It arises from a most unlikely source in light of the exposure of co‐author EJS to the haplotype data of RL Dawkins and others on the polymorphism of the Major Histocompatibility Complex, which is generally assumed to be the most polymorphic region in the genome (spanning ∼4 Mb). The (...) comparison between the magnitude of MHC polymorphism with estimates for the human heavy chain immunoglobulin V locus (spanning ∼1 Mb), suggests IGHV could be many orders of magnitude more polymorphic than the MHC. This conclusion needs airing in the literature as it implies generational churn and soma‐to‐germline gene feedback. Pedigree‐based experimental strategies to resolve the IGHV issue are outlined. (shrink)

The common autoimmune disease type 1 diabetes provides a paradigm for the genetic analysis of multifactorial disease. Disease occurrence is attributable to the interaction with the environment of alleles at many loci interspersed throughout the genome. Their mapping and identification is difficult because the disease-associated alleles occur almost as commonly in patients as in healthy individuals; even the highest-risk genotypes bestow only modest risks of disease. The identification of common quantitative trait loci (QTL) in autoimmune disease and in other common (...) disorders, therefore,requires a very close marriage of genetics and biology. Two QTLs have been identified in human type 1 diabetes: the major histocompatibility complex HLA class II loci and a promoter polymorphism of the insulin gene. The evidence for their primary roles in disease aetiology demonstrates the necessity of combined studies of genetics and biology. Their functions and interaction underpin an emerging picture of the basic causes of the disease and direct analyses towards other candidate genes and pathways. The genetic tools used for QTL identification include transgenesis and gene knockouts, whole genome scanning for linkage, mouse congenic strains, linkage disequilibrium mapping, and the establishment of ancestral haplotypes among disease-associated chromosomes. BioEssays 1999;21:164–174. © 1999 John Wiley & Sons, Inc. (shrink)

T lymphocytes circulate continually throughout the peripheral lymphoid organs, where they scrutinize the surface of cells to detect the presence of nonself protein fragments. During the last years, many facets of T-cell function have been unravelled. After being bound by major histocompatibility complex (MHC) molecules, peptides derived from nonself as well as from self proteins are delivered to the cell surface. A few copies of a nonself peptide “presented” at the cell surface in the context of an (...) MHC molecule can be detected by specific T cells, and suffice to trigger T-cell activation. This paper reviews the requirements imposed on T cells to fulfill this exquisite sensitivity. BioEssays 20:412–422, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Central nervous system (CNS)Abbreviations: CNS=central nervous system; PNS=peripheral nervous system; MS=multiple sclerosis; MBP=myelin basic protein; MHC=major histocompatibility complex; EAE=experimental allergic encephalomyelitis; O‐2A=oligodendrocyte‐type 2 astrocyte; GC=galactocerebroside; GFAP=glial fibrillary acidic protein; FGF=fibroblast growth factor; IGF1=insulin‐like growth factor. regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin‐forming cells — called oligodendrocytes — which are also crucial to the (...) harmonious function of the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination. (shrink)

In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.

I‐J has been regarded as a polymorphic genetic marker controlled by a locus in the major histocompatibility complex (MHC) which is expressed only on functional T cells. However, this antigenic determinant has been found not to be directly encoded by the MHC gene per se but is somatically generated according to the MHC of the cellular environment during ontogeny. This explains the apparent linkage of I‐J to MHC, despite the failure to find the structural gene for I‐J (...) within the MHC. The I‐J paradox provides an instance of a polymorphism that does not follow the standard genetics of Mendelian structural genes. (shrink)

Recently, the development of several strategies based on immunotherapy has raised hopes for a more promising way to treat cancer patients. Here, we describe how interleukin (IL)‐10, a seemingly unlikely candidate, stimulates the immune system in a particularly efficacious way. IL‐10, an omnipotent anti‐inflammatory cytokine, delivers an equally potent immune stimulation in the context of CD8+ T cells and tumor immunity. By activation of tumor‐resident, tumor‐specific CD8+ T cells, pegylated IL‐10 can induce rejection of large and metastasizing tumors in mice. (...) Here, we summarize the mechanisms of action of IL‐10, the reasons why the mechanisms may be crucial for the treatment of cancer patients, and the rationale for applying pegylated IL‐10 in the clinic. (shrink)

The vertebrate immune system uses an impressive arsenal of mechanisms to combat harmful cellular states such as infection. One way is via cells delivering real‐time snapshots of their protein content to the cell surface in the form of short peptides. Specialized immune cells (T cells) sample these peptides and assess whether they are foreign, warranting an action such as destruction of the infected cell. The delivery of peptides to the cell surface is termed antigen processing and presentation, and decades of (...) research have provided unprecedented understanding of this process. However, predicting the capacity for a given peptide to be immunogenic—to elicit a T cell response—has remained both enigmatic and a long sought‐after goal. In the era of big data, a point is being approached where the steps of antigen processing and presentation can be quantified and assessed against peptide immunogenicity in order to build predictive models. This review presents new findings in this area and contemplates challenges ahead. (shrink)

The Westermarck effect (sexual inhibition among individuals raised together) is argued to be mediated olfactorily. Various animals, including humans, distinguish among individuals by scent (significantly determined by MHC genotype), and some avoid cosocialized associates on this basis. Possible models of olfactory mechanisms in humans are evaluated. Evidence suggests aversions develop during an early sensitizing period, attach to persons as much as to their scents, and are more powerful among females than among males. Adult to child aversions may develop similarly, but (...) more likely result from stimulus generalization. This hypothesis accords with current evidence and yields testable predictions (e.g., anosmia will prevent inhibition) that, should they be supported, will conclusively ground the Westermarck effect in a biological mechanism. (shrink)

The serological properties of the major histocompatibility (class I) antigens of mammals have raised many questions about the structure and function of these molecules. Over the past four years the cloning of their gene sequences has begun to provide some of the answers to these questions. The structural analyses have demonstrated close similarities between class I genes of man and mouse, established the existence of numerous class I pseudogenes in human and murine genomes, and indicated the importance of (...) gene conversion events in regulating the sequence diversity of this gene family. In addition, the ability to construct new class I genes in vitro and to transfect cultured murine cells with the synthetic sequences is permitting new tests of the functional organization of these genes in relation to their structure. (shrink)

A perennial concern among scholars of globalization is the relationship between global social formations and national and subnational political and economic developments. While sociological understanding of “the global” has become increasingly rich, stressing the complex relationship between material and cultural pressures, an undertheorized nation state often sits on the receiving end of the sociologist’s model of globalization. The goal of this article is to help move the sociology of globalization out of the analytical trap of global-national dualism by developing (...) an account of the transnationalization of political authority. Building on neo-Marxist and Weberian theories of the transnational, or global state, which explicate the macro-structural dynamics that have led to the transnationalization of the state as such, I look at the process of the transnationalization of political authority from an institutional perspective, one that focuses on processes of transnationalization within, and across, specific state agencies. These theoretical points are empirically motivated through an historical investigation of the transnationalization of monetary authority and its relationship to the international diffusion of policies of austerity from the era of the classical gold standard through the economic crisis of 2008. (shrink)

Yet precisely because the book is so foundational, if we want to understand Strauss’s notoriously careful and complex thinking in these essays, we must also consider them just as Strauss treated philosophers of the past: on their own ...

This chapter provides a short history of the reception of Liang Shuming’s thought in European-language scholarship since 1922. By reviewing a significant number of monographs, edited volumes, and articles published in academic and missionary journals in English, French, and German during the last one hundred years, the chapter aims to provide a historical typology of the multifaceted reception of Liang’s thought through time. In the scholarship reviewed, Liang is variously portrayed as a philosopher, a social reformer or activist, a religious (...) thinker, an educator, a legal thinker, and a political figure. Throughout the years, Liang has been described as a conservative, a restorationist, a fundamentalist, and a modern thinker, and has been labeled a Confucian, a Buddhist, and a populist. The many faces of Liang Shuming laid bare by this short history are revealing of the complexity and tensions of the man and his thought, but also of the interpreters’ gaze and the historical evolution of the academic field in the Euro-American region. The end result is a genealogy of sort—one that challenges some deep-seated assumptions about Liang by tracing them back to a particular and contingent historical moment and by situating them within a broad spectrum of alternative positions vying for attention in the small but diverse discursive space allotted to the thought of Liang Shuming in European-language scholarship. (shrink)

This book provides an analysis of the complex philosophy of Liang Shuming. This twentieth-century thinker opened up a number of paths that were to become central components of modern Chinese philosophy. For the first time, experts are brought together to analyze the complexity of his philosophy, which continues to exert a considerable influence today. This edited volume covers Liang’s multifaceted thought as informed by his many identities as a Buddhist, a Confucian, a Bergsonian, a rural reformer, and a philosopher. (...) The volume will appeal to students, scholars, and general-interest readers. (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)

This paper discusses health policy and systems research in complex and rapidly changing contexts. It focuses on ethical issues at stake for researchers working with government policy makers to provide evidence to inform major health systems change at scale, particularly when the dynamic nature of the context and ongoing challenges to the health system can result in unpredictable outcomes. We focus on situations where ‘country ownership’ of HSR is relatively well established and where there is significant involvement of (...) local researchers and close ties and relationships with policy makers are often present. We frame our discussion around two country case studies with which we are familiar, namely China and South Africa and discuss the implications for conducting ‘embedded’ research. We suggest that reflexivity is an important concept for health system researchers who need to think carefully about positionality and their normative stance and to use such reflection to ensure that they can negotiate to retain autonomy, whilst also contributing evidence for health system change. A research process informed by the notion of reflexive practice and iterative learning will require a longitudinal review at key points in the research timeline. Such review should include the convening of a deliberative process and should involve a range of stakeholders, including those most likely to be affected by the intended and unintended consequences of change. (shrink)

Interferon (IFN) induced during a virus infection mediates antiviral effects both by direct inhibition of virus replication and by influencing the proliferation, differentiation, and chemotaxis of cyto‐toxic lymphocytes which control the infection. Cells from tissue taken from virus‐infected mice are conditioned by IFN to resist lysis by natural killer (NK) cells, while they become increasingly susceptible to lysis by cytotoxic Tlymphocytes (CTL). This is due to marked IFN‐induced biochemical changes, including an up‐regulation of major histocompatibility antigens, which are (...) targets for CTL. Cytopathic viruses, which inhibit cellular RNA and protein synthesis, render target cells refractory to IFN‐mediated protection against NK cells, thereby providing a mechanism for NK cells to mediate antiviral effect by preferentially lysing virus‐infected but not uninfected cells. (shrink)

The model of major transitions in evolution devised by Maynard Smith and Szathmáry has exerted tremendous influence over evolutionary theorists. Although MTE has been criticized for inconsistently combining different types of event, its ongoing appeal lies in depicting hierarchical increases in complexity by means of evolutionary transitions in individuality. In this paper, we consider the implications of major evolutionary events overlooked by MTE and its ETI-oriented successors, specifically the biological oxygenation of Earth, and the acquisitions of mitochondria and (...) plastids. By reflecting on these missed events, we reveal a central philosophical disagreement over the explanatory goals of major transitions theory that has yet to be made explicit in the literature. We go on to argue that this philosophical disagreement is only reinforced by Szathmáry’s recent revisions of MTE in the form of MTE 2.0. This finding motivates us to propose an alternative explanatory strategy: specifically, an interactionist metabolic perspective on major transitions. A metabolic framework not only avoids many of the criticisms that beset classic and revised MTE models, but also accommodates missing events and provides crucial explanatory components for standard major transitions. Although we do not provide a full-blown alternative theory and do not claim to achieve unity, we explain why foregrounding metabolism is crucial for any attempt to capture the major turning points in evolution, and why it does not lead to unmanageable pluralism. (shrink)

This monograph focuses on two major themes of current interest---those of complexity and emergence. Neither of the two concepts is, in the very nature of things, precisely defined or easily comprehended. Complexity is all around us while the sciences often analyze entities and events by making simplifications. But the fault lines in the latter get exposed over larger spans of space and time. Complexity entails emergence that involves discontinuity and novelty in the evolution of complex systems, based on (...) the appearance of distinctive spatial and temporal structures. Underlying an occurrence of emergence is an instability involving the transition from one stable regime to another, where distinct space-time scales acquire relevance across the transition. The structures on the two sides of the transition are characterized by distinct sets of state variables where, on one side of the transition, collective variables make their appearance. -/- Complexity and emergence are viewed in this book in the context of the Kantian noumenal-phenomenal divide. The noumenal reality is the repository of all the complexity that there is, while the phenomenal reality emerges from the noumenal in the process of our perception, interpretation, and inference. The noumenal exists in itself as a self-determined whole, and reveals itself to us in fragmentary patches as skewed projections that we assemble to form our phenomenal world that keeps on emerging ceaselessly. Our own biological evolution and the evolution of our phenomenal world occurs in a mutually consistent process, that can be referred to as co-evolution. -/- We seek regularities in the phenomenal world by means of our scientific theories which are often successful, but that success is fragile as, over larger spans of space and time, anomalies make their appearance, giving a lie to the simplicity and regularity previously presumed to have been unearthed. Simplicity, regularity, and harmony are only fleetingly located in the phenomenal world by means of our theories as these keep on being revised endlessly and often radically, thereby generating a mosaic of theories that becomes ever more complex, indicating a pervasive complexity of the noumenal world from which the phenomenal emerges by way of strictly limited projections. The foundational metaphysics on which this book is based tells us that reality is fundamentally complex, while tiny islands of simplicity, regularity, and harmony are embedded in it in isolated space-time domains. (shrink)

Our world is enormously sophisticated and nature's complexity is literally inexhaustible. As a result, projects to describe and explain natural science can never be completed. This volume explores the nature of complexity and considers its bearing on our world and how we manage our affairs within it.Rescher's overall lesson is that the management of our affairs within a socially, technologically, and cognitively complex environment is plagued with vast management problems and risks of mishap. In primitive societies, failure to understand (...) how things work can endanger a family or, at worst, a clan or tribe. In the modern world, man-made catastrophes on the model of Chernobyl can endanger millions, possibly even risking the totality of human life on our planet. Rescher explains "technological escalation" as a sort of arms race against nature in which scientific progress requires more powerful technology for observation and experimentation, and, conversely, scientific progress requires the continual enhancement of technology. The increasing complexity of science and technology (and, in consequence, of social systems) along with problems growing faster than solutions confront us with major management and decision problems.This study is the first of its kind. There have been many specialized studies of complexity in physics and computation theory, but no overall analysis of the phenomenon. Although Rescher offers a sobering outlook, he also believes that complexity entails mixed blessings: our imperfect knowledge provides a rationale for putting forth our best efforts. Rescher urges us to gear the conduct of life's practical affairs to the demands of a complex world. This highly readable and accessible volume will be of interest to those interested in philosophy, the philosophy of science, science policy studies, and future studies. (shrink)

The idea that consciousness and complexity are closely related has been a major driver of the popularity of integrated information theory of consciousness, despite its major formal, phenomenological, and neuroscientific shortcomings. Here, I argue that we can recover this intuition by replacing its biologically neutral notion of complexity with an evolutionary one that I shall dub “pathological complexity.”.

Complex vocal learning, the capacity to imitate new sounds, underpins the evolution of animal vocal cultures and song dialects and is a key prerequisite for human speech and song. Due to its relevance for the understanding of cultural evolution and the biology and evolution of language and music, the trait has gained much scholarly attention. However, while we have seen tremendous progress with respect to our understanding of its morphological, neurological and genetic aspects, its peculiar phylogenetic distribution has remained (...) elusive. Intriguingly, animals as distinct as hummingbirds and humpback whales share well-developed vocal learning capacity in common with humans, while this ability is quite limited in nonhuman primates. Yet, solving this ‘vocal learning conundrum’ may shed light on the constraints ancestral humans overcame to unleash their vocal capacities. To this end I consider major constraints and functions that have been proposed. I highlight an especially promising ecological constraint, namely the spatial dimensionality of the environment. Based on an informal comparative review, I suggest that complex vocal learning is associated with three-dimensional habitats such as air and water. I argue that this is consistent with recent theoretical advances—i.e., the coercion-avoidance and dimensionality hypotheses—and with the long-standing hypothesis that mate choice is a major driver of the evolution and origin of complex vocal learning. However, I stress that multiple functions may apply and that quantitative phylogenetic comparative methods should be employed to finally resolve the issue. (shrink)

Background: how mind functions is subject to continuing scientific discussion. A simplistic approach says that, since no convincing way has been found to model subjective experience, mind cannot exist. A second holds that, since mind cannot be described by classical physics, it must be described by quantum physics. Another perspective concerns mind's hypothesized ability to interact with the world of quanta: it should be responsible for reduction of quantum wave packets; physics producing 'Objective Reduction' is postulated to form the basis (...) for mind-matter interactions. This presentation describes results derived from a new approach to these problems. It is based on well-established biology involving physics not previously applied to the fields of mind, or consciousness studies, that of critical feedback instability. -/- Methods: 'self-organized criticality' in complexity biology places system loci of control at critical instabilities, physical properties of which, including information properties, are presented. Their elucidation shows that they can model hitherto unexplained properties of experience. -/- Results: All results depend on physical properties of critical instabilities. First, at least one feed-back or feed-forward loop must have feedback gain, g = 1: information flows round the loop impress perfect images of system states back on themselves: they represent processes of perfect self-observation. This annihilates system quanta: system excitations are instability fluctuations, which cannot be quantized. Major results follow: -/- 1. Information vectors representing criticality states must include at least one attached information loop denoting self-observation. -/- 2. Such loop structures are attributed a function, 'registering the state's own existence', explaining -/- a. Subjective 'awareness of one's own presence' -/- b. How content-free states of awareness can be remembered (Jon Shear) -/- c. Subjective experience of time duration (Immanuel Kant) -/- d. The 'witness' property of experience – often mentioned by athletes 'in the zone' -/- e. The natural association between consciousness and intelligence -/- This novel, physically and biologically sound approach seems to satisfactorily model subjectivity. -/- Further significant results follow: -/- 1. Registration of external information in excited states of systems at criticality reduces external wave-packets: the new model exhibits 'Objective Reduction' of wave packets. -/- 2. High internal coherence (postulated by Domash & Penrose) leading to a. Non-separable information vector bundles. b. Non-reductive states (Chalmers's criterion for experience). -/- 3. Information that is: a. encoded in coherence negentropy; b. non-digitizable, and therefore c. computationally without digital equivalent (posited by Penrose). -/- Discussion and Conclusions: instability physics implies anharmonic motion, preventing excitation quantization, and totally different from the quantum physics of simple harmonic motion at stability. Instability excitations are different from anything hitherto conceived in information science. They can model aspects of mind never previously treated, including genuine subjectivity, objective reduction of wave-packets, and inter alia all properties given above. (shrink)

Some demonstrative expressions, those we might term ‘bare demonstratives’, appear without any appended descriptive content (e.g. occurrences of ‘this’ or ‘that’ simpliciter). However, it seems that the majority of demonstrative occurrences do not follow this model. ‘Complex demonstratives’ is the collective term I shall use for phrases formed by adjoining one or more common nouns to a demonstrative expression (e.g. ‘that cat’, ‘this happy man’) and I will call the combination of predicates immediately concatenated with the demonstrative in such (...) phrases the ‘matrix’ of the expression. The question, then, is how we should construe the logical form of such expressions within a semantic theory for our language; and I wish to suggest that some recent answers to this question are, in fact, mistaken. The structure of the paper is as follows: first, I wish to highlight two (often underlying) assumptions about the nature of noun phrases in general, and suggest that, if they are both adopted, they apparently constrain the possible accounts of the logical form of complex demonstratives to just three options. The second and third parts of the paper will be concerned with expanding these options and arguing that none of them are adequate; thus the major part of the paper is concerned with the negative claim that the most obvious moves to make in this area must actually fail on closer inspection. The fourth and final section will then (very briefly) sketch the positive thesis of the paper: that we can deliver a clear and cohesive account of complex demonstratives, armed simply with elements which we will draw from David Kaplan’s theory of demonstratives, but only at the cost of rejecting (or at least refining) one assumption we recognised initially. (shrink)

This paper introduces Deleuze’s philosophy of becoming in a system theoretic framework and proposes an alternative ontological foundation to the study of systems and complex systems in particular. A brief critique of systems theory and the difficulties apparent in it is proposed as an introduction to the discussion. Following is an overview aimed at providing access to the ‘big picture’ of Deleuze’s revolutionary philosophical system with emphasis on a system theoretic approach and terminology. The major concepts of Deleuze’s (...) ontology—difference, virtuality, multiplicity, assemblages, quasi-causation, becoming, intensity and progressive determination are introduced and discussed. Deleuze’s work is a radical departure from the dogma of western philosophy that guides the foundations of science and systems theory. It replaces identity with difference and being with becoming; in other words, it provides systems theory with an ontological ground based on change, heterogeneity and the inexhaustible novelty-producing process that underlies all phenomena. The conceptual tools made available by this philosophy seem to capture the fundamental aspects of complexity and complex systems much better than the current conceptual system that is based on static transcendent ontological entities. (shrink)

Leishmania major infection of inbred mice leads to a major dichotomous response—death or survival—that depends on the strain of mice. This finding has motivated efforts to locate genetic determinants of disease susceptibility. Genotyping studies have confirmed a complex multilocus trait, but studies directed at the biology of the response suggest identifiable components of susceptibility that may direct the genetic investigations. A confluence of parasite variables—residence in macrophages, class II-dependent immunity, and avoidance of early IL-12 induction—with host factors—a (...) prominent helper T-cell precursor frequency to a dominant parasite epitope and a bias in IL-4 gene activation—conspires to drive an aberrant immune response in animals that suffer fatal disease. These insights may lead to an understanding of factors that focus responses on dominant antigens and that mold the naive T-cell repertoire. Collectively, such factors might contribute to the pathogenesis of other infectious and autoimmune diseases. BioEssays 21:510–518, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Learning theory has frequently been applied to language acquisition, but discussion has largely focused on information theoretic problems—in particular on the absence of direct negative evidence. Such arguments typically neglect the probabilistic nature of cognition and learning in general. We argue first that these arguments, and analyses based on them, suffer from a major flaw: they systematically conflate the hypothesis class and the learnable concept class. As a result, they do not allow one to draw significant conclusions about the (...) learner. Second, we claim that the real problem for language learning is the computational complexity of constructing a hypothesis from input data. Studying this problem allows for a more direct approach to the object of study—the language acquisition device—rather than the learnable class of languages, which is epiphenomenal and possibly hard to characterize. The learnability results informed by complexity studies are much more insightful. They strongly suggest that target grammars need to be objective, in the sense that the primitive elements of these grammars are based on objectively definable properties of the language itself. These considerations support the view that language acquisition proceeds primarily through data-driven learning of some form. (shrink)

This article highlights a somewhat neglected aspect of love : their complexity. We suggest distinguishing between three major related types of emotional complexity: emotional diversity, emotional ambivalence, and emotional behavior. The notion of emotional complexity has far-reaching implications for understanding emotions and our wellbeing. This is illustrated by examining the notion of emotional complexity in two common yet complex phenomena in the romantic realm: romantic compromises and polyamory.

The economic crisis is also a crisis for economic theory. Most analyses of the evolution of the crisis invoke three themes, contagion, networks and trust, yet none of these play a major role in standard macroeconomic models. What is needed is a theory in which these aspects are central. The direct interaction between individuals, firms and banks does not simply produce imperfections in the functioning of the economy but is the very basis of the functioning of a modern economy. (...) This book suggests a way of analysing the economy which takes this point of view. The economy should be considered as a complex adaptive system in which the agents constantly react to, influence and are influenced by, the other individuals in the economy. In such systems which are familiar from statistical physics and biology for example, the behaviour of the aggregate cannot be deduced from the behaviour of the average, or "representative" individual. Just as the organised activity of an ants’ nest cannot be understood from the behaviour of a "representative ant" so macroeconomic phenomena should not be assimilated to those associated with the "representative agent". This book provides examples where this can clearly be seen. The examples range from Schelling’s model of segregation, to contributions to public goods, the evolution of buyer seller relations in fish markets, to financial models based on the foraging behaviour of ants. The message of the book is that coordination rather than efficiency is the central problem in economics. How do the myriads of individual choices and decisions come to be coordinated? How does the economy or a market, "self organise" and how does this sometimes result in major upheavals, or to use the phrase from physics, "phase transitions"? The sort of system described in this book is not in equilibrium in the standard sense, it is constantly changing and moving from state to state and its very structure is always being modified. The economy is not a ship sailing on a well-defined trajectory which occasionally gets knocked off course. It is more like the slime described in the book "emergence", constantly reorganising itself so as to slide collectively in directions which are neither understood nor necessarily desired by its components. (shrink)

Complex Pleasure deals with questions of literary feeling in eight major German writers—Lessing, Kant, Hölderlin, Nietzsche, Musil, Kafka, Trakl, and Benjamin. On the basis of close readings of these authors Stanley Corngold makes vivid the following ideas: that where there is literature there is complex pleasure; that this pleasure is complex because it involves the impression of a disclosure; that this thought is foremost in the minds of a number of canonical writers; that important literary works (...) in the German tradition—fiction, poetry, critique—can be illuminated through their treatment of literary feeling; and, finally, that the conceptual terms for these forms of feeling continually vary. The types of feeling treated in Complex Pleasure include wit (the startling perception of likeness) and the disinterested pleasure of aesthetic judgment; Hölderlin’s “swift conceptual grasp,” in which “the tempo of the process of thought is stressed”; “artistic imagination,” mood, sadistic enjoyment, rapturous distraction, homonymic dissonance, and courage as a mode of literary experience. At the same time, through the deftness, range, and surprise of its execution, the book itself conveys complex pleasure. The reader will also find fascinating, hitherto untranslated material by Nietzsche (“On Moods”) and Kafka (important sections from his journals and from his unfinished novel The Boy Who Sank Out of Sight). (shrink)

An extended analysis compared to observations shows that modern “globalised” world civilisation has passed through the invisible “complexity threshold”, after which usual “spontaneous”, empirically driven kind of development (“invisible hand” etc.) cannot continue any more without major destructive tendencies. A much deeper, non-simplified understanding of real interaction complexity is necessary in order to cope with such globalised world development problems. Here we introduce the universal definition, fundamental origin, and dynamic equations for a major related quantity of (systemic) risk (...) characterising real complex system development tendencies at any level of dynamics. Practically important conclusions are derived, opening further detailed applications in economy, finance and development practice. (shrink)

Are fragile majorities capable of opening themselves to deep-rooted and new ethnic and cultural pluralism? What role does education play in this process? Based on ten years of comparative research, Fragile Majorities and Education is a nuanced study of ethnic dominance, linguistic integration of immigrants, and diversity in education. Ethnic relations are often depicted in an oversimplified framework where a clear dominant majority exercises power over various minorities. In many societies worldwide, however, this model does not hold true. In some (...) countries, two or more groups possess relatively equal power to control the state and impose their definitions of the nation, as is the case with Flemish speakers and French speakers in Belgium, and with Catholics and Protestants in Northern Ireland. In other instances, such as in Quebec or Catalonia, clearly identifiable majorities are nonetheless minorities at a larger nation-state level, which creates a situation of ambiguous ethnic dominance. Marie McAndrew analyzes and clarifies these complex situations through the lens of education as a means for both maintaining and transforming ethnic boundaries and identities. Deeply insightful and meticulously researched, Fragile Majorities and Education is a groundbreaking contribution to the field of ethnic studies. (shrink)

Taking the lead from complexity theory and complex systems methodology, the article argues that we are engaged in a contradictory process when encountering, analysing and dealing with complexity. We face opposite tendencies that indicate an in-built dynamic between the increase of complexity and its reduction. The increase partly comes through evolution, defined as the transmission of information and partly from the desire for a human-built world that functions more efficiently. The reduction of complexity is due partly to the necessity (...) of minimizing unwanted and unintended consequences of its increase, and partly due to the continued re-alignment between social systems and their environments. The article examines the public debate about human stem cell research, the debates in the 18th century about the free circulation of commodities and opinions, and the attempts to provide answers to the question debated between Einstein and Freud: why war? The article concludes by arguing that the plea for a re-alignment of scientific disciplines will not suffice. Instead, the study of the co-evolution between science and society offers itself as a strategic research site by focusing on the dynamic interplay between the increase of complexity and its reduction. (shrink)

Systems change requires complex interventions. Cross-sector partnerships face the daunting task of addressing complex societal problems by aligning different backgrounds, values, ideas and resources. A major challenge for CSPs is how to link the type of partnership to the intervention needed to drive change. Intervention strategies are thereby increasingly based on Theories of Change. Applying ToCs is often a donor requirement, but it also reflects the ambition of a partnership to enhance its transformative potential. The current use (...) of ToCs in partnering efforts varies greatly. There is a tendency for a linear and relatively simple use of ToCs that does limited justice to the complexity of the problems partnerships aim to address. Since partnership dynamics are already complex and challenging themselves, confusion and disagreement over the appropriate application of ToCs is likely to hamper rather than enhance the transformative potential of partnerships. We develop a complexity alignment framework and a diagnostic tool that enables partnerships to better appreciate the complexity of the context in which they operate, allowing them to adjust their learning strategy. This paper applies recent insights into how to deal with complexity from both the evaluation and theory of change fields to studies investigating the transformative capacity of partnerships. This can serve as a check to define the challenges of partnering projects and can help delineate the societal sources and layers of complexity that cross-sector partnerships deal with such as failure, insufficient responsibility taking and collective action problems at four phases of partnering. (shrink)