Protein aggregation has been studied for at least 3 decades, and many of the principles that regulate this event are relatively well understood. Here, however, we present a different perspective to explain why proteins aggregate: we argue that aggregation may occur as a side‐effect of the lack of one or more natural partners that, under physiologic conditions, would act as chaperones. This would explain why the same surfaces that have evolved for functional purposes are also those that favour aggregation. In (...) the course of reviewing this field, we substantiate our hypothesis with three paradigmatic examples that argue for the generality of our proposal. An obvious corollary of this hypothesis is, of course, that targeting the physiological partners of a protein could be the most direct and specific approach to designing anti‐aggregation molecules. Our analysis may thus inform a different strategy for combating diseases of protein aggregation and misfolding. (shrink)

Combinations of molecules, of biological individuals, or of chemical processes can produce effects that are not simply attributable to the constituents. Such non-redundant causality warrants recognition of those coherences as ontologically significant whenever that efficacy is relevant. With respect to such interaction, the effective coherence is more real than are the components. This ontological view is a variety of structural realism and is also a kind of process philosophy. The designation ‘process structural realism’ (PSR) seems appropriate.

On Thursday, August 21, 1862, Edmond and Jules de Goncourt registered in their Journal a short entry on the nature of life: “Qu’est-ce que la vie? L’usufruit d’une agrégation de molecules”—What is life? The usufruct of an aggregation of molecules. Although the extraordinary chronicles of the social and cultural life of the Second French Empire written by the Goncourt brothers includes names of their most distinguished contemporaries, the writers, artists, politicians and socialites they befriended outnumber by far the (...) scientists. It is almost certain that they were never close to Felix Dujardin, a distinguished microbiologist and member of the French Academy of Sciences. In 1835, Dujardin had started crushing ciliates under the microscope and observed that the tiny cells exuded a jellylike substance, which he described as a “gelée vivante” and was eventually named “protoplasm” by Johann E. Purkinje and Hugo von Mohl. The small note written by the Goncourts in their journal is an indica. (shrink)

Previous chapter Flowing Multiplicities and Fibers Since the flowing multiplicities had no substantial being based either on “differentiated elements” or a “common center of unification,” they were constituted by a certain “number of dimensions” or enclosed in a supple “envelop.” But they were, at the same time, “transforming themselves into each other.” The flux of the being was therefore simultaneously composed of molecules in constant motion and of changing aggregates which constantly - Philosophie – Nouvel article.

How could the self be a substance? There are various ways in which it could be, some familiar from the history of philosophy. I shall be rejecting these more familiar substantivalist approaches, but also the non-substantival theories traditionally opposed to them. I believe that the self is indeed a substance—in fact, that it is a simple or noncomposite substance—and, perhaps more remarkably still, that selves are, in a sense, self-creating substances. Of course, if one thinks of the notion of substance (...) as an outmoded relic of prescientific metaphysics—as the notion of some kind of basic and perhaps ineffablestuff—then the suggestion that the self (or indeed anything) is a substance may appear derisory. Even what we ordinarilycall‘stuffs’—gold and water and butter and the like—are, it seems, more properly conceived of as aggregates of molecules or atoms, while the latter are not appropriately to be thought of as being ‘made’ of any kind of ‘stuff’ at all. But this only goes to show that we need to think in terms of a more sophisticated notion of substance—one which may ultimately be traced back to Aristotle's conception of a ‘primary substance’ in theCategories, and whose heir in modern times is W. E. Johnson's notion of the ‘continuant’. It is the notion, that is, of a concrete individual capable of persisting identically through qualitative change, a subject of alterable predicates that is not itself predicable of any further subject. (shrink)

Multicellularity in the cellular slime mold Dictyostelium discoideum is achieved by the expression of two types of cell–cell adhesion sites. The EDTA‐sensitive adhesion sites are expressed very early in the developmental cycle and a surface glycoprotein of 24000 Da is known to be responsible for these sites. The EDTA‐resistant contact sites begin to accumulate on the cell surface at the aggregation stage of development. Several glycoproteins have been implicated in the EDTA‐resistant type of cell–cell binding and the best characterized one (...) has an Mr of 80000 (gp80). gp80 mediates cell–cell binding via homophilic interaction and its cell binding site has been mapped to an octapeptide sequence. The mechanism by which gp80 mediates cell–cell adhesion will be discussed. (shrink)

Recent successes of systems biology clarified that biological functionality is multilevel. We point out that this fact makes it necessary to revise popular views about macromolecular functions and distinguish between local, physico-chemical and global, biological functions. Our analysis shows that physico-chemical functions are merely tools of biological functionality. This result sheds new light on the origin of cellular life, indicating that in evolutionary history, assignment of biological functions to cellular ingredients plays a crucial role. In this wider picture, even if (...) aggregation of chance mutations of replicator molecules and spontaneously self-assembled proteins led to the formation of a system identical with a living cell in all physical respects but devoid of biological functions, it would remain an inanimate physical system, a pseudo-cell or a zombie-cell but not a viable cell. In the origin of life scenarios, a fundamental circularity arises, since if cells are the minimal units of life, it is apparent that assignments of cellular functions require the presence of cells and vice versa. Resolution of this dilemma requires distinguishing between physico-chemical and biological symbols as well as between physico-chemical and biological information. Our analysis of the concepts of symbol, rule and code suggests that they all rely implicitly on biological laws or principles. We show that the problem is how to establish physico-chemically arbitrary rules assigning biological functions without the presence of living organisms. We propose a solution to that problem with the help of a generalized action principle and biological harnessing of quantum uncertainties. By our proposal, biology is an autonomous science having its own fundamental principle. The biological principle ought not to be regarded as an emergent phenomenon. It can guide chemical evolution towards the biological one, progressively assigning greater complexity and functionality to macromolecules and systems of macromolecules at all levels of organization. This solution explains some perplexing facts and posits a new context for thinking about the problems of the origin of life and mind. (shrink)

How could the self be a substance? There are various ways in which it could be, some familiar from the history of philosophy. I shall be rejecting these more familiar substantivalist approaches, but also the non-substantival theories traditionally opposed to them. I believe that the self is indeed a substance—in fact, that it is a simple or noncomposite substance—and, perhaps more remarkably still, that selves are, in a sense, self-creating substances. Of course, if one thinks of the notion of substance (...) as an outmoded relic of prescientific metaphysics—as the notion of some kind of basic and perhaps ineffablestuff—then the suggestion that the self is a substance may appear derisory. Even what we ordinarilycall‘stuffs’—gold and water and butter and the like—are, it seems, more properly conceived of as aggregates of molecules or atoms, while the latter are not appropriately to be thought of as being ‘made’ of any kind of ‘stuff’ at all. But this only goes to show that we need to think in terms of a more sophisticated notion of substance—one which may ultimately be traced back to Aristotle's conception of a ‘primary substance’ in theCategories, and whose heir in modern times is W. E. Johnson's notion of the ‘continuant’. It is the notion, that is, of a concrete individual capable of persisting identically through qualitative change, a subject of alterable predicates that is not itself predicable of any further subject. (shrink)

During the Middle Ages, philosophers and theologians argued over the extramental reality of universal forms or essences. In the early modern period, the relation between subjectivity and objectivity, the individual self and knowledge of the outside world, was a rich subject of debate. Today, there is considerable argument about the relation between spontaneity and determinism within the evolutionary process, whether a principle of spontaneous self-organization as well as natural selection is at work in the aggregation of molecules into cells (...) and the development of primitive forms of life into complex organisms. In _Subjectivity, Objectivity and Intersubjectivity_, Joseph A. Bracken proposes that what is ultimately at stake here is the age-old problem of the relationship between the One and the Many, universality and particularity on different levels of existence and activity within nature. Bracken rejects traditional models of this relationship, wherein either the One or the Many is presupposed to have priority over the other. He instead suggests that a new social ontology—one that is grounded in a theory of universal intersubjectivity—protects both the concrete particularity of individual entities in their specific relations to one another and their enduring corporate reality as a stable community or environment within Nature. What emerges is a bold reimagining of the sometimes strained relationship between religion and science. Bracken's clear writing, sophisticated philosophical analysis, and exemplary scholarship will lend this new work an enthusiastic appreciation by readers with deep interests in philosophy and philosophical theology. (shrink)

We hypothesize that life began not with the first self‐reproducing molecule or metabolic network, but as a prebiotic ecology of co‐evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, (...) while fusion created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co‐evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self‐reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed. BioEssays 28: 399–412, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The study of biodiversity spans many disciplines and includes data pertaining to species distributions and abundances, genetic sequences, trait measurements, and ecological niches, complemented by information on collection and measurement protocols. A review of the current landscape of metadata standards and ontologies in biodiversity science suggests that existing standards such as the Darwin Core terminology are inadequate for describing biodiversity data in a semantically meaningful and computationally useful way. Existing ontologies, such as the Gene Ontology and others in the Open (...) Biological and Biomedical Ontologies (OBO) Foundry library, provide a semantic structure but lack many of the necessary terms to describe biodiversity data in all its dimensions. In this paper, we describe the motivation for and ongoing development of a new Biological Collections Ontology, the Environment Ontology, and the Population and Community Ontology. These ontologies share the aim of improving data aggregation and integration across the biodiversity domain and can be used to describe physical samples and sampling processes (for example, collection, extraction, and preservation techniques), as well as biodiversity observations that involve no physical sampling. Together they encompass studies of: 1) individual organisms, including voucher specimens from ecological studies and museum specimens, 2) bulk or environmental samples (e.g., gut contents, soil, water) that include DNA, other molecules, and potentially many organisms, especially microbes, and 3) survey-based ecological observations. We discuss how these ontologies can be applied to biodiversity use cases that span genetic, organismal, and ecosystem levels of organization. We argue that if adopted as a standard and rigorously applied and enriched by the biodiversity community, these ontologies would significantly reduce barriers to data discovery, integration, and exchange among biodiversity resources and researchers. (shrink)

Trehalose is a natural disaccharide with a remarkable ability to stabilize biomolecules. In recent years, trehalose has received growing attention as a neuroprotective molecule and has been tested in experimental models for different neurodegenerative diseases. Although the underlying neuroprotective mechanism of trehalose's action is unclear, one of the most important hypotheses is autophagy induction. The chaperone‐like activity of trehalose and the ability to modulate inflammatory responses has also been reported. There is compelling evidence that the dysfunction of autophagy and aggregation (...) of misfolded proteins contribute to the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Therefore, given the linking between trehalose and autophagy induction, it appears to be a promising therapy for AD. Herein, the published studies concerning the use of trehalose as a potential therapy for AD are summarized, providing a rationale for applying trehalose to reduce Alzheimer's pathology. (shrink)

Biology in the popular mind remains tied to the doctrines of the struggle forsurvival and the survival of the fittest. Physics is linked to the heat deathof the universe – the inexorable march towards greater disorder,increasing entropy. Our field, on the other hand, focuses on orderedstructures, molecules and crystals, and their aggregates, and what holdsthem together. The philosophy of chemistry is centered on affinity,cohesion, the architecture of the very small, attraction, harmony, and, ifyou permit, beauty. Our discipline is (...) the voice of the twenty-first century,a message, a clarion call of life, of hope. This paper addresses failures ofreductionist and deterministic claims in the face of the cussedness ofchemical facts. It will examine uncertainty principles, Edmund Whitaker'spostulates of impotence, Gerald Holton's themata, Isaiah Berlin's warning –and the wisdom of the Chinese. We can teach the world the need for humilityin the face of the wonder and mystery of our world. (shrink)

Microbes often live in association with dense multicellular aggregates, especially biofilms, and the construction of these aggregates typically requires microbial cells to produce public goods, such as enzymes and signaling molecules. Public-goods producers are, in turn, vulnerable to exploitation by free-rider cells that consume the public goods without paying for their production costs. The cell population of a biofilm or other microbial aggregates are expected to pass through bottlenecks due to a wide range of factors, such (...) as antibiotic treatments and dispersal. The goal of this article is to make the case for the relevance of population bottlenecks at shaping the social interactions within microbial aggregates. The effect of bottlenecks on microbial aggregates is complex in that bottlenecks can favor producers under certain circumstances, but not in others. The concept of the Volunteer’s Dilemma from game theory will be used to motivate the hypothesis that this partly occurs because of how bottlenecks alter the risk of being a producer in a microbial aggregate. Finally, the role of bottlenecks in the microbial world impacts key issues in evolutionary biology, including the importance of ecology at shaping social evolution, and the evolution of multicellularity from unicellular ancestors. (shrink)

What I suggest we can see in this brief overview of the literature is an extensive interpenetration on both sides of these debates between scientific, political, and social values. Important shifts in political and social values were of course occurring over the same period, some of them in parallel with, and perhaps even contributing to, these transitions I have been speaking of in evolutionary discourse. The developments that I think of as at least suggestive of possible parallels include the progressive (...) encroachment of public values into the private domain of post-World War II American life, the cold war, the rise of consumerism, and the flowering of what Christopher Lasch calls a “narcissistic individualism.”35 In popular language, the 1960s gave birth to the “me” generation. Perhaps the most tantalizing analogue is suggested by Barbara Ehrenreich's argument for the emergence of a new meaning of masculinity — an ideal of masculinity measured not by commitment, responsibility, or success as family provider, but precisely by the strength of a man's autonomy in the private sphere, his resistance to the demands of a hampering female.36 It is tempting to speculate about possible connections between changes in scientific discourse and developments in the social and political spheres, but such connections, however suggestive, would clearly have to be demonstrated.For now, however, I want to focus on another kind of change —a transformation not so much in the social or political sphere as in the scientific sphere. I make this turn, or return, in support of a more complex account of scientific change that incorporates reverberations within the scientific communty along with social and political changes.In the 1960s, all of biology was undergoing a major transformation in direct response to the dramatic successes of molecular biology. These successes seemed to completely vindicate the values on which the molecular revolution was premised — namely, simplicity and mechanism. Following the victory of Watson and Crick, and of others after them, the fever of that endeavor swept through biology leaving in its wake a new standard of science, and of scientific discourse — one predicated on clarity, simplicity, and analyzability; on the definition of legitimate questions as those capable of clear and unambiguous answers. Every biological discipline felt it — even evolutionary biology, which in some respects was at the furthest pole. Perhaps precisely because it seemed conceptually so remote, evolutionary biology may have felt it most of all. Lewontin inadvertently provides us with some direct support for this view. Indeed, he begins his introduction to Population Biology and Evolution with the following remarks: The twenty years since World War II have seen a vindication in biology of our faith in the Cartesian method as a way of doing science. Some of the most fundamental and interesting problems of biology have been solved or are very nearly solved by an analytic technique that is now loosely called “molecular biology.” But it is not specifically the “molecular” aspect of biology of the last twenty years that has led to its success. It is, rather, the analytic aspect, the belief that by breaking systems down into their component parts, by simplifying them or using simpler organisms, one can learn about more complex systems. As it happens, the problems that were attacked and are being attacked by this method lead to answers in terms of molecules and cell organelles.... There is a host of problems in biology, however, that has been much neglected in these twenty exciting years, because the answers to them cannot be meaningfully framed in molecular and cellular terms.37Lewontin is referring, of course, to problems in evolution. The remainder of his remarks is devoted to an argument for the applicability of the method, if not the content, of molecular biology to these problems. He writes, “It is not the case that molecular biology is Cartesian and analytic while population biology is holistic. Population biology is properly analytic and operates, within the framework of its own problems, by the process of simplification, analysis, and resynthesis.”38 With these remarks, he leads into the criticism of the “holists” who have “held up progress.”This new ethic of simplicity, clarity, and mechanism — embodying the very virtues lauded by Williams — was explicitly carried into evolutionary biology in the name of scientific progress. As it happened, the values implied also fit conveniently well with other values — each set of values providing crucial support for the other.However substantive the scientific gains may have been in some respects, the net effect of this ethic has also been a systematic “perceptual bias” — a bias with profound practical consequences for the entire program of methodological individualism in evolutionary biology, if not elsewhere as well. It may well be that the whole is equivalent to the reconstituted aggregate of its parts, if, in the process of aggregation or summation, all possible interactions among the parts are included. But if certain kinds of interactions are systematically excluded, our confidence in that program necessarily founders. My claim here is that such systematic exclusion does occur, and that it occurs on a number of different levels. To briefly review the interlocking kinds of “bias” that I see occurring in practice, I suggest the following schematic listing:On the most general level: The ethic of simplicity — the privileging of certain values, even certain methodologies, as having an a priori superior claim to scientific credibility.Only slightly less general, and crucially related, is the equation of “scientific” with “tractible”: Given the techniques of analysis available, the equation of science with what we can do inevitably leads to a systematic technical bias favoring simplicity. That is, because we don't know how to model complex dynamics, nonlinear interactions are systematically biased against because of the limitations of our technical know-how. The consequences of this equation of the scientific with the tractible are greatly compounded by the additional equation between what we can do and what is — that is, by our temptation to confuse tractibility with reality.Finally, and also closely related, a further kind of elision occurs even within the confines of tractibility. This kind of elision — taking the form almost of inferring tractibility from one's prior assumptions of what is real — is exemplified by the history of a mathematical ecology of mutualism. Even when mutualism can be introduced into the same technical machinery, it is still not pursued. The basic assumption is that competition is what is real, not because it is easier to model, but because it is what we expect. When the actual difficulties of modeling competition are then in turn suppressed, as in the Robert May story, what we have, given the temptation to equate the tractible with the real, is the possibility of a truly self-fulfilling prophecy. (shrink)

No one knows yet how to organize, in a simple yet predictive form, the knowledge concerning the anatomical, biophysical, and molecular properties of neurons that are accumulating in thousands of publications every year. The situation is not dissimilar to the state of Chemistry prior to Mendeleev's tabulation of the elements. We propose that the patterns of presence or absence of axons and dendrites within known anatomical parcels may serve as the key principle to define neuron types. Just as the positions (...) of the elements in the periodic table indicate their potential to combine into molecules, axonal and dendritic distributions provide the blueprint for network connectivity. Furthermore, among the features commonly employed to describe neurons, morphology is considerably robust to experimental conditions. At the same time, this core classification scheme is suitable for aggregating biochemical, physiological, and synaptic information. (shrink)

Mulliken proposed an Aufbauprinzip for the molecules on the basis of molecular spectroscopy while establishing, point by point, his concept of molecular orbit. It is the concept of electronic state which becomes the lever for his attribution of electronic configurations to a molecule. In 1932, the concept of orbit was transmuted into that of the molecular orbital to integrate the probabilistic approach of Born and to achieve quantitative accuracy. On the basis of the quantum works of Hund, Wigner, Lennard-Jones (...) and group theory, he suggested the fragment method to establish the characteristics of molecular orbital for polyatomic molecules. These developments make it possible to bring elements of thought on the relation between a molecular whole and its parts . An operational realism combined with the second law of thermodynamics can pave the way for interesting tracks in the mereological study of chemical systems. (shrink)

My focus is on aggregation of individual value rankings of alternatives to a collective value ranking. This is compared with aggregation o individual prefrences to a collective preference. While in an individual preference ranking the alternatives are ordered in accordance with one’s preferences, the order in a value ranking expresses one’s comparative evaluation of the alternatives, from the best to the worst. I suggest that, despite their formal similarity as rankings, this difference in the nature of individual inputs in two (...) aggregation scenarios has important implications: The kind of procedure that looks fine for aggregation of judgments is inappropriate for aggregation of preferences. The procedure I have in mind consists in similarity maximization, or – more precisely – in minimization of the average distance from individual inputs. When applied to judgment aggregation, this procedure can also be approached from the epistemic perspective: the questions are posed concerning its advantages as a truth-tracker. From that perspective, what matters is not only the probability of the outcome of the procedure being true, but also the expected verisimilitude of the outcome: its expected distance from truth. (shrink)

How can the propositional attitudes of several individuals be aggregated into overall collective propositional attitudes? Although there are large bodies of work on the aggregation of various special kinds of propositional attitudes, such as preferences, judgments, probabilities and utilities, the aggregation of propositional attitudes is seldom studied in full generality. In this paper, we seek to contribute to filling this gap in the literature. We sketch the ingredients of a general theory of propositional attitude aggregation and prove two new theorems. (...) Our first theorem simultaneously characterizes some prominent aggregation rules in the cases of probability, judgment and preference aggregation, including linear opinion pooling and Arrovian dictatorships. Our second theorem abstracts even further from the specific kinds of attitudes in question and describes the properties of a large class of aggregation rules applicable to a variety of belief-like attitudes. Our approach integrates some previously disconnected areas of investigation. (shrink)

This paper proves two theorems for homogeneous juries that arise from different solutions to the problem of aggregation of dichotomous choice. In the first theorem, negative correlation increases the competence of the jury, while positive correlation has the opposite effect. An enlargement of the jury with positive correlation can be detrimental up to a certain size, beyond which it becomes beneficial. The second theorem finds a family of distributions for which correlation has no effect on a jury’s competence. The approach (...) allows us to compute the bounds on a jury’s competence as the maximum and minimum probability of it being correct for a given individual competence and dependence structure. (shrink)

"In his third lecture Crick anticipates events and trends that have in fact come to pass in the past four decades, including the increasing use of computer technology and robotics in mind-brain research, explorations into right-side versus left-side uses of the brain, and controversies surrounding the existence of the soul."--BOOK JACKET.

My focus is on aggregation of individual value rankings of alternatives to a collective value ranking. This is compared with aggregation o individual prefrences to a collective preference. While in an individual preference ranking the alternatives are ordered in accordance with one’s preferences, the order in a value ranking expresses one’s comparative evaluation of the alternatives, from the best to the worst. I suggest that, despite their formal similarity as rankings, this difference in the nature of individual inputs in two (...) aggregation scenarios has important implications: The kind of procedure that looks fine for aggregation of judgments is inappropriate for aggregation of preferences. The procedure I have in mind consists in similarity maximization, or – more precisely – in minimization of the average distance from individual inputs. When applied to judgment aggregation, this procedure can also be approached from the epistemic perspective: the questions are posed concerning its advantages as a truth-tracker. From that perspective, what matters is not only the probability of the outcome of the procedure being true, but also the expected verisimilitude of the outcome: its expected distance from truth. (shrink)

A necessary and sufficient condition for linear aggregation of SSB utility functionals is presented. Harsanyi's social aggregation theorem for von Neumann–Morgenstern utility functions is shown to be a corollary to this result. Two generalizations of Fishburn and Gehrlein's conditional linear aggregation theorem for SSB utility functionals are also established.

How can the propositional attitudes of several individuals be aggregated into overall collective propositional attitudes? Although there are large bodies of work on the aggregation of various special kinds of propositional attitudes, such as preferences, judgments, probabilities and utilities, the aggregation of propositional attitudes is seldom studied in full generality. In this paper, we seek to contribute to filling this gap in the literature. We sketch the ingredients of a general theory of propositional attitude aggregation and prove two new theorems. (...) Our first theorem simultaneously characterizes some prominent aggregation rules in the cases of probability, judgment and preference aggregation, including linear opinion pooling and Arrovian dictatorships. Our second theorem abstracts even further from the specific kinds of attitudes in question and describes the properties of a large class of aggregation rules applicable to a variety of belief-like attitudes. Our approach integrates some previously disconnected areas of investigation. (shrink)

Cerreia-Vioglio et al. :341–375, 2011) have proposed a very general axiomatisation of preferences in the presence of ambiguity, viz. Monotonic Bernoullian Archimedean preference orderings. This paper investigates the problem of Arrovian aggregation of such preferences—and proves dictatorial impossibility results for both finite and infinite populations. Applications for the special case of aggregating expected-utility preferences are given. A novel proof methodology for special aggregation problems, based on model theory, is employed.

Polyglutamine (polyQ) diseases are genetically inherited neurodegenerative disorders. They are caused by mutations that result in polyQ expansions of particular proteins. Mutant proteins form intranuclear aggregates, induce cytotoxicity and cause neuronal cell death. Protein interaction data suggest that polyQ regions modulate interactions between coiled‐coil (CC) domains. In the case of the polyQ disease spinocerebellar ataxia type‐1 (SCA1), interacting proteins with CC domains further enhance aggregation and toxicity of mutant ataxin‐1 (ATXN1). Here, we suggest that CC partners interacting with the (...) polyQ region of a mutant protein, increase its aggregation while partners that interact with a different region reduce the formation of aggregates. Computational analysis of genetic screens revealed that CC‐rich proteins are highly enriched among genes that enhance pathogenicity of polyQ proteins, supporting our hypothesis. We therefore suggest that blocking interactions between mutant polyQ proteins and their CC partners might constitute a promising preventive strategy against neurodegeneration. (shrink)

We discuss Herzberg’s :319–337, 2015) treatment of linear aggregation for profiles of infinitely many finitely additive probabilities and suggest a natural alternative to his definition of linear continuous aggregation functions. We then prove generalizations of well-known characterization results due to :410–414, 1981). We also characterize linear aggregation of probabilities in terms of a Pareto condition, de Finetti’s notion of coherence, and convexity.

Two types of interleukin 1 (IL‐1α and IL‐1β) have been defined by purifying the molecules from activated human peripheral blood cells, followed by cloning and expressing the molecules in Escherichia coli. Both types of IL‐1 stimulate proliferation and differentiation of T‐ and B‐lymphocytes and induce cartilage proteoglycan degradation but differ in other properties. For example, demineralization and appears to be a major mediator in the pathogenesis of joint erosion in rheumatoid arthritis. Synthetic adjuvants elicit the production of IL‐1 (...) separate from endogenous pyrogen, and this property is required for the new generation of vaccines based on antigens produced by recombinant DNA technology. (shrink)

The article proceeds upon the assumption that the beliefs and degrees of belief of rational agents satisfy a number of constraints, including: consistency and deductive closure for belief sets, conformity to the axioms of probability for degrees of belief, and the Lockean Thesis concerning the relationship between belief and degree of belief. Assuming that the beliefs and degrees of belief of both individuals and collectives satisfy the preceding three constraints, I discuss what further constraints may be imposed on the aggregation (...) of beliefs and degrees of belief. Some possibility and impossibility results are presented. The possibility results suggest that the three proposed rationality constraints are compatible with reasonable aggregation procedures for belief and degree of belief. (shrink)

The possibility of domain restrictions that allow the consistent use of majority-based aggregators for rankings of objects has been widely explored. This paper extends this exploration to structures in which equivalence relations or classifications are aggregated, and shows that there is very limited scope for such restrictions in the binary structure of Mirkin and in the unary structure of Maniquet and Mongin. We develop a hybrid structure that combines binary and unary conditions on the aggregator, and that allows the use (...) of a majority-based aggregator if and only if each object is eligible for inclusion in no more than two categories out of some greater number. We also show that in many circumstances, the surjectivity requirement of Maniquet and Mongin implicitly introduces binary conditions on the aggregator, and that their structure is entailed by the hybrid structure introduced here. (shrink)

The article shows that a Paretian social welfare function can be history independent and time consistent only if a stringent set of conditions is verified. Individual utilities must be additive. The social welfare function must be a linear combination of these utilities. Social preferences are stationary only if, in addition, all individuals have the same constant discount rate. The results are implemented in two frameworks: deterministic dynamic choice and dynamic choice under uncertainty. The applications highlight that the conditions are unlikely (...) to be met by individual preferences, and that they severely restrict social preferences. (shrink)

If humans subject animals to painful, damaging, or frightening procedures to achieve scientific progress, then the very least that humankind can do is to insist that regulations be put in place to protect animals and that they be properly implemented and enforced. However, recent practice in the United Kingdom suggests that this is not the case. Europe’s new regime on the protection of animals used for scientific purposes—Directive 2010/63—must act as a catalyst for significant change and is a significant recognition (...) of the intrinsic value of animals. Before this Directive, the cost/benefit analysis undertaken in the United Kingdom allowed for a large margin of error so that animal welfare was an aggregated concept, and any aggregated finding of “adequate” animal welfare was not militated by individual cases of exacerbated animal detriment. The recognition that each animal has value as an individual means that the levels of animal welfare or protection expected of scientific establishments can no longer simply be those that are, in generic terms, appropriate for the aggregated mass of animals. Instead, the welfare standards applied are appropriate and rendered effectual for all individual animals. (shrink)

I propose a straightforward reconciliation of Leibniz’s conception of bodies as aggregates of simple substances (i.e., monads) with his doctrine that bodies are the phenomena of perceivers, without in the process saddling him with any equivocations. The reconciliation relies on the familiar idea that in Leibniz’s idiolect, an aggregate of Fs is that which immediately presupposes those Fs, or in other words, has those Fs as immediate requisites. But I take this idea in a new direction. Taking notice of (...) the fact that Leibniz speaks of three respects in which one thing may immediately presuppose others--i.e., with respect to its being, its existence, and its reality--I argue that a phenomenon having its being in one perceiving substance (monad) can plausibly be understood to presuppose other perceiving substances (monads) in two of these respects. Accordingly, good sense can be made of both the claim that a phenomenon in one monad is an aggregate of other monads (in Leibniz’s technical sense of 'aggregate') and the (equivalent) claim that the latter monads are constituents of the phenomenon (in his technical sense of 'constituent'). So understood, the two conceptions of body are perfectly compatible, just as Leibniz seems to think. (shrink)

Reuse is well established in molecular evolution; some analogies from this better understood field may help suggest specific aspects of reuse of neural circuits.

Since the emergence of the innovative field of artificial intelligence in the 1960s, the late Hubert Dreyfus insisted on the ontological distinction between man and machine, human and artificial intelligence. In the different editions of his classic and influential book What computers can’t do, he posits that an algorithmic machine can never fully simulate the complex functioning of the human mind—not now, nor in the future. Dreyfus’ categorical distinctions between man and machine are still relevant today, but their relation has (...) become more complex in our increasingly data-driven society. We, humans, are continuously immersed within a technological universe, while at the same time ubiquitous computing, in the words of computer scientist Mark Weiser, “forces computers to live out here in the world with people” The cell phone reader. Peter Lang Publishing, New York, 2006, p 20). Dreyfus’ ideas are therefore challenged by thinkers such as Weiser, Kevin Kelly, Bruno Latour, Philip Agre, and Peter Paul Verbeek, who all argue that humans are much more intrinsically linked to machines than the original dichotomy suggests—they have evolved in concert. Through a discussion of the classical concepts of individuum and ‘authenticity’ within Western civilization, this paper argues that within the ever-expanding data-sphere of the twenty-first century, a new concept of man as ‘aggregate of data’ has emerged, which further erodes and undermines the categorical distinction between man and machine. This raises political and ethical questions beyond the confines of technology and artificial intelligence. Moreover, this seemingly never-ending debate on what computers should do provokes the philosophical necessity to once again define the concept of what it is to be ‘human.’. (shrink)

This chapter unfolds a central philosophical problem of statistical mechanics. This problem lies in a clash between the Static Probabilities offered by statistical mechanics and the Dynamic Probabilities provided by classical or quantum mechanics. The chapter looks at the Boltzmann and Gibbs approaches in statistical mechanics and construes some of the great controversies in the field — for instance the Reversibility Paradox — as instances of this conflict. It furthermore argues that a response to this conflict is a critical choice (...) that shapes one's understanding of statistical mechanics itself, namely, whether it is to be conceived as a special or fundamental science. The chapter details some of the pitfalls of the latter ‘globalist’ position and seeks defensible ground for a kind of ‘localist’ alternative. (shrink)

We reject Moorean holism about value—the view that the value of the whole does not equal the sum of the values of its parts. We propose an alternative aggregative holism according to which the value of a state of affairs is the sum of the values of its constituent states. But these constituents must be evaluated in situ.

본고는 불교에서 자아심리학의 성립가능성을 보고자 한다. 불교의 인간론에서 인간은 기능적 존재이면서 가능적 존재이다. 자아를 나, 인간으로 볼 수 있다면 불교에서 인간은 오온의 기능 집합체로 볼 수 있다. 이러한 기능을 나열적으로 보여줌으로써 자아에 대한 포괄적 정의가 성립한다. 기능의 가능성이 최대한 발현된 것이 인간의 본래적 측면이라는 점에서 자아에 대한 본래적 정의가 성립한다. 이와는 반대로 기능의 발현가능성이 억제되는 것은 자아에 대한 비본래적 정의에 해당한다. 본래적 정의에 의한 오온은 오법온으로, 비본래적 정의에 의한 오온은 오취온으로 부를 수 있다. 또한 자아를 발생적 관점에서 연기론에 따라서 정의할 (...) 수 있다. 자아인 명색과 유는 무명과 행, 애와 취에 의해서 발생한다는 자아에 대한 발생적 정의가 성립한다. 사성제적 관점에서 보면 고라는 자아와 집이라는 원인, 멸이라는 자아의 소멸과 소멸로 나아가는 도라는 원인을 자아에 대한 생멸적 정의라고 볼 수 있다.BR 비본래적 정의와 본래적 정의를 바탕으로 범부의 자아와 성인의 자아를 구분할 수 있고, 이를 바탕으로 자아정체성이 범부와 성인의 두 차원에서 성립함을 볼 수 있다. 범부의 차원에서 자아와 자아정체성은 유위법으로, 세속적 진리의 차원에서 세워지고, 성인의 차원에서 자아와 자아정체성은 무아적 자아로 성립하게 된다. 서구의 자아심리학에서 다루는 자아의 기능과 방어기제는 자아의 원인이 되는 번뇌에서 다룰 수 있을 것이다. 자아의 정의, 자아의 발생, 자아의 정체성, 자아의 기능과 기제를 불교적 관점에서 볼 수 있게 된다. 그러므로 불교의 자아심리학이라는 영역의 성립가능성을 보게 된다. (shrink)

The aggregation of consistent individual judgments on logically interconnected propositions into a collective judgment on those propositions has recently drawn much attention. Seemingly reasonable aggregation procedures, such as propositionwise majority voting, cannot ensure an equally consistent collective conclusion. The literature on judgment aggregation refers to that problem as the discursive dilemma. In this paper, we motivate that many groups do not only want to reach a factually right conclusion, but also want to correctly evaluate the reasons for that conclusion. In (...) other words, we address the problem of tracking the true situation instead of merely selecting the right outcome. We set up a probabilistic model analogous to Bovens and Rabinowicz (2006) and compare several aggregation procedures by means of theoretical results, numerical simulations and practical considerations. Among them are the premise-based, the situation-based and the distance-based procedure. Our findings confirm the conjecture in Hartmann, Pigozzi and Sprenger (2008) that the premise-based procedure is a crude, but reliable and sometimes even optimal form of judgment aggregation. (shrink)

It is a commonplace in the analytic geometry of physical space-time that an extended straight line segment, having positive length, is treated as “consisting of” unextended points, each of which has zero length. Analogously, time intervals of positive duration are resolved into instants, each of which has zero duration.

This paper is about the role of interpersonal comparisons in Harsanyi's aggregation theorem. Harsanyi interpreted his theorem to show that a broadly utilitarian theory of distribution must be true even if there are no interpersonal comparisons of well-being. How is this possible? The orthodox view is that it is not. Some argue that the interpersonal comparability of well-being is hidden in Harsanyi's premises. Others argue that it is a surprising conclusion of Harsanyi's theorem, which is not presupposed by any one (...) of the premises. I argue instead that Harsanyi was right: his theorem and its weighted-utilitarian conclusion do not require interpersonal comparisons of well-being. The key to making sense of this possibility is to treat Harsanyi's weights as dimensional constants rather than dimensionless numbers. (shrink)

Vasubandhu’s arguments against atomism in Viṃśikā stanzas 12–13 are not strong enough to disprove that atoms are simple partless substances. However, if we take the special composition question into consideration, Viṃśikā stanza 13ab can be regarded as an objection to so-called series-style answers, which results in an undesirable conclusion for the opponents, i.e. the Vaibhāṣikas. A step back to a simple bonding answer is not a good choice for the Vaibhāṣikas in responding to this objection because the simple bonding answer (...) leads to other difficulties and because some notions in Vaibhāṣika atomic theory entail multigrade relations in the material aggregates of atoms. Hence, the objection to series-style answers still makes sense in the refutation of Buddhist atomism through the claim that atoms are not proper parts of a material aggregate. (shrink)