A widely accepted tenet of evolutionary biology is that spontaneous mutations occur randomly with regard to their fitness effect. However, since the mutation rate varies along a genome and this variation can be subject to selection, organisms might evolve lower mutation rates at loci where mutations are most deleterious or increased rates where mutations are most needed. In fact, mechanisms of targeted hypermutation are known in organisms ranging from bacteria to humans. Here we review the main forces driving (...) the evolution of local mutation rates and identify the main limiting factors. Both targeted hyper‐ and hypomutation can evolve, although the former is restricted to loci under very frequent positive selection and the latter is severely limited by genetic drift. Nevertheless, we show how an association of repair with transcription or chromatin‐associated proteins could overcome the drift limit and lead to non‐random hypomutation along the genome in most organisms.Editor's suggested further reading in BioEssays Stress‐induced mutation via DNA breaks in Escherichia coli: A molecular mechanism with implications for evolution and medicine Abstract. (shrink)

This research note challenges the idea that Random Somatic Mutations are entirely random, highlighting their non-equiprobable nature and their influence on evolution, involution, or indeterminacy. It recalls the Neutrosophic Theory of Evolution, extending Darwin’s theory, and emphasizes the importance of distinguishing between different senses of ‘random mutation’ in evolutionary theory.

Dans cet article je propose la double-thèse : du caractère « vague » (tel que défini dans la littérature logico-sémantique contemporaine) de la notion de hasard (chance) par opposition au caractère « non-vague » de celle d’aléatoire (randomness) ; du lien entre la vagueness et le pouvoir explicatif du hasard et la non-vagueness et la capacité descriptive de l’aléatoire, lequel plaide en faveur d’usages distincts de ces deux notions. Pour défendre la première thèse, j’ai recours aux définitions des notions de (...) hasard et d’aléatoire et à un exemple de l’histoire des sciences (la théorie du chaos). Pour appuyer la seconde, je fais appel à des exemples scientifiques : la variation dans la théorie darwinienne de l’évolution, la mutation génétique dans la synthèse moderne et la dérive génétique dans la théorie neutraliste de l’évolution. (shrink)

The current mainstream in cancer research favours the idea that malignant tumour initiation is the result of a genetic mutation. Tumour development and progression is then explained as a sort of micro-evolutionary process, whereby an initial genetic alteration leads to abnormal proliferation of a single cell that leads to a population of clonally derived cells. It is widely claimed that tumour progression is driven by natural selection, based on the assumption that the initial tumour cells acquire some properties that (...) endow such cells with a selective advantage over the normal cells from which the tumour cells are derived. The standard view assumes that the transformed bodily cell somehow acquires "responsiveness" to natural selection independently of the whole organism to which the cell belongs. Yet, it is never explained where such an acquired capacity to respond to natural selection by the individual bodily cell comes from. This situation poses many difficult questions that so far have been left unanswered. For example, there is no explanation why some cells belonging to an organised whole and as such having no independent capacity for survival, apparently become 'independent' entities, able to respond to selective pressures in an autonomous fashion and then to be evaluated by natural selection. Hereunder it is argued that such a qualitative change cannot be the consequence of specific genetic mutations. Moreover, it is shown that natural selection is unlikely to be acting within the organism during tumour development and progression and that tumour evolution is a random, non-adaptive process, driven by no fundamental biological principle. Thus, mutations in the so-called oncogenes and tumour suppressor genes observed in epithelial cancers (that constitute more than 90% of all cancers) are not the result of selection for better cellular growth or survival under restrictive conditions. Instead, here it is suggested that they are the consequence of genetic drift acting upon gene functions that become non-relevant, either for the individual or the species fitness, once the organism is past its reproductive prime and as such, they also become superfluous for cell survival in the short term. It is proposed that the origin of cancer is epigenetic and it is a consequence of the need for a continued turnover of the individuals that constitute a species. (shrink)

A long-standing challenge to evolutionary theory has been whether it can explain the origin of complex organismal features. We examined this issue using digital organisms—computer programs that self-replicate, mutate, compete and evolve. Populations of digital organisms often evolved the ability to perform complex logic functions requiring the coordinated execution of many genomic instructions. Complex functions evolved by building on simpler functions that had evolved earlier, provided that these were also selectively favoured. However, no particular intermediate stage was essential for evolving (...) complex functions. The first genotypes able to perform complex functions differed from their non-performing parents by only one or two mutations, but differed from the ancestor by many mutations that were also crucial to the new functions. In some cases, mutations that were deleterious when they appeared served as stepping-stones in the evolution of complex features. These findings show how complex functions can originate by random mutation and natural selection. (shrink)

Conceptual developments have defined concrete questions about the timing and precise location of cellular pattern formation. Plants in general, and the trichomes of Arabidopsis in particular, are remarkably suited for research on these problems. Genetic analysis requires the quantitative characterizations of the developmental processes by which patterning occurs. Larkin et al.(1) have provided measures of the non‐random distances between trichomes. They have also obtained evidence about the cell lineages leading to trichome development, and this evidence constrains the possible role (...) of intracellular programs. Continued genetic analysis may call for the identification of mutations that are expressed only during development and whose effects are corrected before the phenotype matures. (shrink)

Contingency-theorists have gestured to a series of phenomena such as random mutations or rare Armageddon-like events as that which accounts for evolutionary contingency. These phenomena constitute a class, which may be aptly called the ‘sources of contingency’. In this paper, I offer a probabilistic conception of what it is to be a source of contingency and then examine two major candidates: chance variation and genetic drift, both of which have historically been taken to be ‘chancy’ in a number of (...) different senses. However,contrathe gesturing of contingency-theorists, chance variation and genetic drift are not always strong sources of contingency, as they can be non-chancy in at least one sense that opposes evolutionary contingency. The probabilistic conception offered herein allows for sources of contingency to appropriately vary in strength. To this end, I import Shannon’sinformation entropyas a statistical measure for systematically assessing the strength of a source of contingency, which is part and parcel of identifying sources of contingency. In brief, the higher the entropy, the greater the strength. This is also empirically significant because molecular, mutational, and replicative studies often contain sufficient frequency or probability data to allow for entropies to be calculated. In this way, contingency-theorists can evaluate the strength of a source of contingency in real-world cases. Moreover, the probabilistic conception also makes conceptual room for the converse of sources of contingency: ‘sources of directionality’, which ought to be recognised, as they can interact with genuine sources of contingency in undermining evolutionary contingency. (shrink)

The article explores a change taking place today in the fields of biology and social anthropology, signaling a shared desire to transcend the heuristic effects of the opposition between nature and culture. Acceptance of the idea that random mutations are the sole driving force behind the process of natural selection overlooks the agentive capacity of non-human living beings, revealing an anthropocentric inspiration. To critique the rhetoric surrounding the principle of natural selection, I turn to the anthropology of Tim Ingold (...) and his analysis of the metaphors that illustrate the principle. I disagree with the author, however, when he argues that these metaphors do not adequately illustrate neo-Darwinian premises. Instead, I believe that they are faithful since their apparent contradiction expresses the unease of neo-Darwinian theory itself when it combines randomness and teleology. New currents in biology, such as biosemiotics, attribute evolutionary importance to epigenetic changes. From the evolutionary perspective, they also highlight the importance of recognizing that the entire lived world possesses the capacity for agency, not just human beings. Within social anthropology, the so-called ontological turn and multispecies ethnography have been working with a new conception of the person, extendible to non-human beings, including the latter to compose a single collective with humans. Thus we can observe an attempt on the part of biologists and anthropologists alike to move beyond anthropocentrism, producer and product of the opposition between nature and culture. (shrink)

It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as being of viral (...) descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. (shrink)

There is an argument that has recently been deployed in favor of thinking that the mind is mostly (or even exclusively) composed of cognitive modules; an argument that draws from some ideas and concepts of evolutionary and of developmental biology. In a nutshell, the argument concludes that a mind that is massively composed of cognitive mechanisms that are cognitively modular (henceforth, c-modular) is more evolvable than a mind that is not c-modular (or that is scarcely c-modular), since a cognitive mechanism (...) that is c-modular is likely to be biologically modular (henceforth, b-modular), and b-modular characters are more evolvable (e.g., Sperber 2002, Carruthers 2005). In evolutionary biology, the evolvability of a character in an organism is understood as the “organism’s capacity to facilitate the generation of non-lethal selectable phenotypic variation from random mutation” with respect to that character. Here I will argue that the notion of cognitive modularity needed to make this argument plausible will have to be understood in terms of the biological notion of variational independence; that is, it will have to be understood in such a way that a cognitive feature is c-modular only if few or no other morphological changes (cognitive and not) are significantly correlated with variations of that feature arising in members of the relevant population. I will also argue that all –except for (possibly) one—of the connotations contained in a cluster of notions of cognitive modularity widely accepted in some of the mainstream currents of thought in classical cognitive science, are simply irrelevant to the argument. In order to argue for this, I will have to examine the question as to whether there are any strong theoretical connections between (1) those connotations and (2) notions of modularity accepted in biology, specially in evolutionary and in developmental biology, that are thought to be most relevant to arguments to the effect that biological modularity enhances evolvability. (shrink)

Philosophers of science have used various formulations of the "random mutation--natural selection" scheme to explain the development of scientific knowledge. But the uncritical acceptance of this evolutionary model has led to substantive problems concerning the relation between fact and theory. The primary difficulty lies in the fact that those who adopt this model (Popper and Kuhn, for example) are led to claim that theories arise chiefly through the processes of relatively random change. Systems theory constitutes a general (...) criticism of this model insofar as it demonstrates the necessity of supplementing this mechanism with the non-random influences exercised by the internal organization of a system on its own development. (shrink)

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent (...) studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. (shrink)

Darwinian evolutionary theory has two key terms, variations and biological selection, which finally lead to survival of the fittest variant. With the rise of molecular genetics, variations were explained as results of error replications out of the genetic master templates. For more than half a century, it has been accepted that new genetic information is mostly derived from random error-based events. But the error replication narrative has problems explaining the sudden emergence of new species, new phenotypic traits, and genome (...) innovations as a sudden single event. Meanwhile, it is recognized that errors cannot explain the evolution of genetic information, genetic novelty, and complexity. Now, empirical evidence establishes the crucial role of non-random genetic content editors, such as viruses, diversity generating retroelements, and other RNA networks, to produce new genetic information, complex regulatory control, inheritance vectors, genetic identity, immunity, new sequence space, evolution of complex organisms, and evolutionary transitions. (shrink)

In this short paper, we propose a special class of quantum systems with implicit quantum uncertainties without any probability structure followed by the dynamical behavior of the systems. When a system is deterministic or random, it does not capture the essence of freedom of choice (FOC), which is the ability to make decisions followed by one’s preferences, free from both deterministic and random outcomes. The proposed special class of quantum systems contains non-deterministic yet non-random outcomes, and so (...) they open the possibility of having FOC within the systems. We also examine examples of such a special class of quantum systems that do not violate the postulates of quantum mechanics. (shrink)

We present a model for genome evolution, comprising biologically plausible events such as transpositions inside the genome and insertions of exogenous sequences. This model attempts to formulate a minimal proposition accounting for key statistical properties of genomes, avoiding, as far as possible, unsupportable hypotheses for the remote evolutionary past. The statistical properties that are observed in genomic sequences and are reproduced by the proposed model are: (i) deviations from randomness at different length scales, measured by suitable algorithms, (ii) a special (...) form of size distribution (power law distribution) characterising different levels of genome organisation in the non‐coding, and (iii) extensive resemblance in the alternation of coding and non‐coding regions at several length scales (self‐similarity) in long genomic sequences of higher eukaryotes. BioEssays 23:647–656, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Although we use randomness when we don’t know any better, a principle of indifference cannot be used to explain anything interesting or fundamental. For example, in thermodynamics it can be shown that the real explanatory work is being done by the Second Law, not the equal a priori probability postulate. But to explain the interesting Second Law, many physicists try to retreat to a “random explanation,” which fails. Looking at this problem from a different perspective reveals a natural solution: (...) boundary-based explanations that arguably should be viewed as no less fundamental than other physical laws. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate the non‐linear, stochastic (...) dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

Infants use statistical information in their environment, as well as others’ emotional communication, to understand the intentions of social partners. However, rarely do researchers consider these two sources of social information in tandem. This study assessed 2-year-olds’ attributions of intentionality from non-random sampling events and subsequent discrete emotion reactions. Infants observed an experimenter remove five objects from either the non-random minority (18%) or random majority (82%) of a sample and express either joy, disgust, or sadness after each (...) selection. Two-year-olds inferred the experimenter’s intentionality by giving her the object that she had previously selected when she expressed joy or disgust after non-random sampling events, but not when she expressed sadness or sampled at random. These findings demonstrate that infants use both statistical regularities and discrete emotion communication to infer an agent’s intentions. In particular, the present findings show that 2-year-olds infer that an agent can intentionally select a preferred or an undesired object from a sample as a function of the discrete emotion. Implications for the development of inferring intentionality from statistical sampling events and discrete emotion communication are discussed. (shrink)

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of ‘normal science’. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non‐functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena (...) of paramutation and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein‐coding) genes and increase in ‘noncoding’ sequences with developmental complexity; genetic loci termed ‘enhancers’ that control spatiotemporal gene expression patterns during development; and a plethora of ‘intergenic’, overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information. Also see the video abstract here: https://youtu.be/qxeGwahBANw. (shrink)

The levers of natural selection are random genetic mutation, fitness for survival, and reproductive success. Defenders of the evolutionary debunking account (EDA) hold that such mechanisms aren’t likely to produce cognitive faculties that reliably form true moral beliefs. So, according to EDA, given that our cognitive faculties are a product of unguided natural selection, we should be in doubt about the reliability of our moral cognition. Let the term ‘sanspsychism’ describe the view that no supramundane consciousness exists. In (...) arguing against theism, some sanspsychists advance a normative claim about the moral significance of phenomena like sentient suffering. But if no supramundane consciousness exists, our cognitive faculties are a product of unguided natural selection. It follows that if EDA is correct, the sanspsychist should not think that our moral cognition is reliable. So unless the sanspsychist has a defeater for EDA, she should not think herself justified in appealing to normative reasons for denying the existence of God. (shrink)

Although random mutation is central to models of evolutionary change, a lack of clarity remains regarding the conceptual possibilities for thinking about the nature and role of mutation in evolution. We distinguish several claims at the intersection of mutation, evolution, and directionality and then characterize a previously unrecognized category: complex conditioned mutation. Empirical evidence in support of this category suggests that the historically famous fluctuation test should be revisited, and new experiments should be undertaken with (...) emerging experimental techniques to facilitate detecting mutation rates within specific loci at an ultra‐high, individual base pair resolution. (shrink)

Although quantum mechanics can accurately predict the probability distribution of outcomes in an ensemble of identical systems, it cannot predict the result of an individual system. All the local and global hidden variable theories attempting to explain individual behavior have been proved invalid by experiments (violation of Bell’s inequality) and theory. As an alternative, Schrodinger and others have hypothesized existence of free will in every particle which causes randomness in individual results. However, these free will theories have failed to quantitatively (...) explain the quantum mechanical results. In this paper, we take the clue from quantum biology to get the explanation of quantum mechanical distribution. Recently it was reported that mutations (which are quantum processes) in DNA of E. coli bacteria instead of being random were biased in a direction such that the chance of survival of the bacteria is increased. Extrapolating it, we assume that all the particles including inanimate fundamental particles have a will and that is biased to satisfy the collective goals of the ensemble. Using this postulate, we mathematically derive the correct spin probability distribution without using quantum mechanical formalism (operators and Born’s rule) and exactly reproduce the quantum mechanical spin correlation in entangled pairs. Using our concept, we also mathematically derive the form of quantum mechanical wave function of free particle which is conventionally a postulate of quantum mechanics. Thus, we prove that the origin of quantum mechanical results lies in the will (or consciousness) of the objects biased by the collective goal of ensemble or universe. This biasing by the group on individuals can be called as “coherence” which directly represents the extent of life present in the ensemble. So, we can say that life originates out of establishment of coherence in a group of inanimate particles. (shrink)

Randomness, a core concept of gambling, is seen in problem gambling as responsible for the formation of the math-related cognitive distortions, especially the Gambler’s Fallacy. In problem-gambling research, the concept of randomness was traditionally referred to as having a mathematical nature and categorized and approached as such. Randomness is not a mathematical concept, and I argue that its weak mathematical dimension is not decisive at all for the randomness-related issues in gambling and problem gambling, including the correction of the misconceptions (...) and fallacies about probability and statistical concepts applied in gambling. I distinguish between mathematical and nonmathematical dimensions of randomness (the epistemic, the theoretical-methodological, the functional, and the ethical) falling within the general concept, and I argue that both the studies having as object the math-related cognitive distortions among gamblers and the educational programs aiming at correcting them should employ this distinction in their design and content. (shrink)

We show a number of improvements in the use of Hidden Conditional Random Fields for phone classification on the TIMIT and Switchboard corpora. We first show that the use of regularization effectively prevents overfitting, improving over other methods such as early stopping. We then show that HCRFs are able to make use of non-independent features in phone classification, at least with small numbers of mixture components, while HMMs degrade due to their strong independence assumptions. Finally, we successfully apply Maximum (...) a Posteriori adaptation to HCRFs, decreasing the phone classification error rate in the Switchboard corpus by around 1% – 5% given only small amounts of adaptation data. (shrink)

Evolutionary gradualism, the randomness of mutations, and the hypothesis that natural selection exerts a pervasive and substantial influence on evolutionary outcomes are pair-wise logically independent. Can the claims about selection and mutation be used to formulate an argument for gradualism? In his Genetical Theory of Natural Selection, R.A. Fisher made an important start at this project in his famous “geometric argument” by showing that a random mutation that has a smaller effect on two or more phenotypes will (...) have a higher average fitness than a random mutation that has a larger phenotypic effect. Motoo Kimura’s demonstration that a gene’s probability of fixation depends on both the selection coefficient and the effective population size shows that Fisher’s argument for gradualism was mistaken. Here we analyze Fisher’s argument and explain how Kimura’s theory leads to a conclusion that Fisher did not anticipate. We identify a fallacy that reasoning about fitness differences and their evolutionary consequences should avoid. We then distinguish forward-directed from backward-directed versions of gradualism. The backward-directed thesis about a single mutation may be correct, but the forward-directed thesis is not. After that we consider a sequence of random mutations that all affect the same cluster of phenotypes and Allen Orr’s idea that there is an optimal sequence of mutation sizes, moving from larger to smaller as the population approaches a fixed optimum. This provides a likelihood justification for a forward-directed version of gradualism when there is a fixed optimum, but it also provides an argument against forward-directed gradualism if the optimum shifts substantially as the population evolves. Finally, we consider whether genome-wide association studies (GWASs) can furnish empirical evidence that bears on the truth of gradualism. The version of gradualism that GWASs directly bear on concerns the phenotypic effect size of a gene after it arises by mutation and has reached an appreciable frequency, not the phenotypic size of the mutation event itself. (shrink)

One central tenet of the Modern Evolutionary Synthesis , and the consensus view among biologists until now, is that all genetic mutations occur by “chance” or at “random” with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the “chance” vs “directed” character of mutations . In fact, some argue that mutations due to a particular kind (...) of mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis’ consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb’s analysis of genetic mutations and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of “evolutionary chance,” which I claim is the Modern Synthesis’ consensus view and a reformulation of Darwin’s most influential idea of “chance” variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis’ paradigm. (shrink)

A cell contains many copies of mitochondrial DNA. The distribution of a mitochondrial gene mutation in a cell culture is governed by the way in which the mtDNA molecules of a cell are replicated and partitioned between the two daughter cells during mitosis. Assuming that this partition process is random, we describe the evolution of the mitochondrial genetic state of a cell culture. The mutated mtDNA is ultimately segregated and the rate of the trend to segregation is relatively (...) slow. It is nevertheless greatly accelerated if the model takes into account the spatial mtDNA partition by the mitochondrial compartments. (shrink)

The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some (...) cases, EZH2 overexpression also leads to its use of non‐histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. (shrink)

We study degree-theoretic properties of reals that are not random with respect to any continuous probability measure (NCR). To this end, we introduce a family of generalized Hausdorff measures based on the iterates of the “dissipation” function of a continuous measure and study the effective nullsets given by the corresponding Solovay tests. We introduce two constructions that preserve non-randomness with respect to a given continuous measure. This enables us to prove the existence of NCR reals in a number of (...) Turing degrees. In particular, we show that every \(\Delta ^0_2\) -degree contains an NCR element. (shrink)

En cette entame du troisième millénaire, la musique adresse une question aux autres arts comme aux sciences : comment ajuster les différentes écritures (musicale, mathématique, chorégraphique, biologique...) aux nouvelles matières sur lesquelles ces pensées embrayent? S'il est vrai que le système autonome d'écriture musicale (le solfège), inventé il y a près de 1 000 ans, s'avère désormais en partie inadapté aux nouveaux matériaux sonores qu'il s'agit de composer, la prolifération empirique des simples notations à laquelle on assiste aujourd'hui ne saurait (...) pourvoir aux mutations en jeu : en matière d'écriture musicale, il en va non de simples techniques neutres mais bien de logique musicale, donc de ce qu'un discours ou un développement veulent musicalement dire. S'il s'agit donc en cette affaire de penser les mutations en cours en matière de "logique musicale" et leurs exigences en matière de nouvelles "lettres/notes" musicales, qu'en est-il de soucis semblables dans les autres arts et dans les sciences? Qu'en est-il de mutations équivalentes dans les autres arts, singulièrement dans ceux qui entreprennent de se doter d'une écriture qui leur soit propre (la chorégraphie)? Qu'en est-il surtout dans les sciences, dans les mathématiques bien sûr mais aussi en logique comme dans les sciences ayant à nouer leurs propres lettres à l'impératif galiléen de s'écrire mathématiquement? Comment ce double dispositif (écriture mathématique importée/modes endogènes d'inscription) tend-il aujourd'hui à se nouer en physique, en chimie, en biologie, en informatique? Ce volume rassemble différentes contributions soutenues et discutées lors d'un colloque tenu à l'Ecole normale supérieure (Paris, Ulm) en octobre 2007. (shrink)

We address two points. First, one must explain how different, rare mutations ultimately lead to common psychopathological conditions. The developmental instability model offers one solution. Second, Keller & Miller perhaps miss the major processes other than variation fueled by rare deleterious mutations that account for interesting genetic variation in psychopathology, particularly when single alleles have non-negligible effects: Red Queen processes.

In this paper, we examine the pioneering research on electronic noise—the current fluctuations in electronic circuit devices due to their intrinsic physical characteristics rather than their defects—in Germany and the U.S. during the 1910s–1920s. Such research was not just another demonstration of the general randomness of the physical world Einstein’s work on Brownian motion had revealed. In contrast, we stress the importance of a particular engineering context to electronic noise studies: the motivation to design and improve high-gain thermionic-tube amplifiers for (...) radio and wired communications. Engineering scientists’ endeavors to understand electronic noise started in 1918, when Walter Schottky at Siemens formulated a theory of “shot noise,” current fluctuations owing to the random emissions of discrete electrons in a tube. Schottky’s theory was revised and experimentally tested at Siemens, General Electric, and AT&T during the 1920s, leading to the discoveries of several other types of noise and an increasing interest in the thermal fluctuations in electronic circuits. In 1925–1928, J.B. Johnson and Harry Nyquist at Bell Labs developed a theory of thermal noise for any electrical resistor at a non-zero temperature. Although these studies were initiated to chart the fundamental performance limit of electronic technology, they ended up assisting the empirical determination of individual electronic components’ characteristics. (shrink)

We investigate the question “To what extent can random reals be used as a tool to establish number theoretic facts?” Let $\text{2-\textit{RAN\/}}$ be the principle that for every real $X$ there is a real $R$ which is 2-random relative to $X$. In Section 2, we observe that the arguments of Csima and Mileti [3] can be implemented in the base theory $\text{\textit{RCA}}_0$ and so $\text{\textit{RCA}}_0+\text{2-\textit{RAN\/}}$ implies the Rainbow Ramsey Theorem. In Section 3, we show that the Rainbow Ramsey (...) Theorem is not conservative over $\text{\textit{RCA}}_0$ for arithmetic sentences. Thus, from the Csima—Mileti fact that the existence of random reals has infinitary-combinatorial consequences we can conclude that $\text{2-\textit{RAN\/}}$ has non-trivial arithmetic consequences. In Section 4, we show that $\text{2-\textit{RAN\/}}$ is conservative over $\text{\textit{RCA}}_0+\text{\textit{B\/}$\,\Sigma$}_2$ for $\Pi^1_1$-sentences. Thus, the set of first-order consequences of $\text{2-\textit{RAN\/}}$ is strictly stronger than $P^-+I\Sigma_1$ and no stronger than $P^-+\text{\textit{B\/}$\,\Sigma$}_2$. (shrink)

Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the “modern synthesis” of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress‐induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress‐induced mutation that are being revealed experimentally in (...) laboratory settings provide compelling models for mutagenesis that propels pathogen–host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double‐strand‐break‐dependent stress‐induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti‐evolvability therapeutics for infectious disease and cancer. (shrink)

We consider two ways one might use algorithmic randomness to characterize a probabilistic law. The first is a generative chance* law. Such laws involve a nonstandard notion of chance. The second is a probabilistic* constraining law. Such laws impose relative frequency and randomness constraints that every physically possible world must satisfy. While each notion has virtues, we argue that the latter has advantages over the former. It supports a unified governing account of non-Humean laws and provides independently motivated solutions to (...) issues in the Humean best-system account. On both notions, we have a much tighter connection between probabilistic laws and their corresponding sets of possible worlds. Certain histories permitted by traditional probabilistic laws are ruled out as physically impossible. As a result, such laws avoid one variety of empirical underdetermination, but the approach reveals other varieties of underdetermination that are typically overlooked. (shrink)

Explaining the behaviour of ecosystems is one of the key challenges for the biological sciences. Since 2000, new-mechanicism has been the main model to account for the nature of scientific explanation in biology. The universality of the new-mechanist view in biology has been however put into question due to the existence of explanations that account for some biological phenomena in terms of their mathematical properties (mathematical explanations). Supporters of mathematical explanation have argued that the explanation of the behaviour of ecosystems (...) is usually provided in terms of their mathematical properties, and not in mechanistic terms. They have intensively studied the explanation of the properties of ecosystems that behave following the rules of a non-random network. However, no attention has been devoted to the study of the nature of the explanation in those that form a random network. In this paper, we cover that gap by analysing the explanation of the stability behaviour of the microbiome recently elaborated by Coyte and colleagues, to determine whether it fits with the model of explanation suggested by the new-mechanist or by the defenders of mathematical explanation. Our analysis of this case study supports three theses: (1) that the explanation is not given solely in terms of mechanisms, as the new-mechanists understand the concept; (2) that the mathematical properties that describe the system play an essential explanatory role, but they do not exhaust the explanation; (3) that a non-previously identified appeal to the type of interactions that the entities in the network can exhibit, as well as their abundance, is also necessary for Coyte and colleagues’ account to be fully explanatory. From the combination of these three theses we argue for the necessity of an integrative pluralist view of the nature of behaviour explanation when this is given by appealing to the existence of a random network. (shrink)

By pitting John Cage against Andy Warhol, Arthur Danto shows how the arts themselves were gripped by a progressive logic that aimed at only one goal: to overcome the gap between art and life. The non‐tautological reading preserves a fundamental, philosophical difference between commonplace and art objects. The semantical space accounts for the aboutness of the work and is thus the necessary condition for something to be an artwork. Together with other Pop artists, Rauschenberg transformed the Artworld, while Cage aimed (...) at a re‐enfranchisement of the commonplace. Danto writes that his Buddhist phase came to an end when he, as a philosopher, felt the need for theories. The works of Fluxus and Cage, in the end, accepted asylum within the sanctuary of the Artworld, where they became less radical, and perhaps less radical than Pop. (shrink)

The Copenhagen interpretation of quantum mechanics assumes the existence of the classical deterministic Newtonian world. We argue that in fact the Newton determinism in classical world does not hold and in the classical mechanics there is fundamental and irreducible randomness. The classical Newtonian trajectory does not have a direct physical meaning since arbitrary real numbers are not observable. There are classical uncertainty relations: Δq>0 and Δp>0, i.e. the uncertainty (errors of observation) in the determination of coordinate and momentum is always (...) positive (non zero).A “functional” formulation of classical mechanics was suggested. The fundamental equation of the microscopic dynamics in the functional approach is not the Newton equation but the Liouville equation for the distribution function of the single particle. Solutions of the Liouville equation have the property of delocalization which accounts for irreversibility. The Newton equation in this approach appears as an approximate equation describing the dynamics of the average values of the position and momenta for not too long time intervals. Corrections to the Newton trajectories are computed. An interpretation of quantum mechanics is attempted in which both classical and quantum mechanics contain fundamental randomness. Instead of an ensemble of events one introduces an ensemble of observers. (shrink)

A categorical, higher dimensional algebra and generalized topos framework for Łukasiewicz–Moisil Algebraic–Logic models of non-linear dynamics in complex functional genomes and cell interactomes is proposed. Łukasiewicz–Moisil Algebraic–Logic models of neural, genetic and neoplastic cell networks, as well as signaling pathways in cells are formulated in terms of non-linear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks. An algebraic formulation of variable ‘next-state functions’ is extended to a Łukasiewicz–Moisil (...) Topos with an n-valued Łukasiewicz–Moisil Algebraic Logic subobject classifier description that represents non-random and non-linear network activities as well as their transformations in developmental processes and carcinogenesis. The unification of the theories of organismic sets, molecular sets and Robert Rosen’s (M,R)-systems is also considered here in terms of natural transformations of organismal structures which generate higher dimensional algebras based on consistent axioms, thus avoiding well known logical paradoxes occurring with sets. Quantum bionetworks, such as quantum neural nets and quantum genetic networks, are also discussed and their underlying, non-commutative quantum logics are considered in the context of an emerging Quantum Relational Biology. (shrink)

Schnorr randomness is a notion of algorithmic randomness for real numbers closely related to Martin-Löf randomness. After its initial development in the 1970s the notion received considerably less attention than Martin-Löf randomness, but recently interest has increased in a range of randomness concepts. In this article, we explore the properties of Schnorr random reals, and in particular the c.e. Schnorr random reals. We show that there are c.e. reals that are Schnorr random but not Martin-Löf random, (...) and provide a new characterization of Schnorr random real numbers in terms of prefix-free machines. We prove that unlike Martin-Löf random c.e. reals, not all Schnorr random c.e. reals are Turing complete, though all are in high Turing degrees. We use the machine characterization to define a notion of "Schnorr reducibility" which allows us to calibrate the Schnorr complexity of reals. We define the class of "Schnorr trivial" reals, which are ones whose initial segment complexity is identical with the computable reals, and demonstrate that this class has non-computable members. (shrink)