Multidrug resistance (MDR) is developed in a population of somatic mammalian cells in vivo or in vitro when they are selected for resistance to each of a large group of drugs (colchicine, adriamycin, actinomycin D, etc.). It is produced by the amplification of some unknown gene(s) whose product(s) evidently change(s) the plasma membrane permeability of a cell to a selective agent and to other unrelated compounds. A large specific genomic region (150–250 kbp) undergoes amplification in MDR cells selected for the (...) resistance to different drugs. Amplified DNA is located in homogeneously staining regions of chromosomes, double minute chromosomes and small chromatin bodies – episome‐like structures that replicate out of the S‐phase of a cell cycle. The selection of MDR cell variants is accompanied by regular karyotypic evolution specific for this type of drug resistance. (shrink)

We identify two aspects of the problem of maintaining perceptual stability despite an observer's eye movements. The first, visual direction constancy, is the (egocentric) stability of apparent positions of objects in the visual world relative to the perceiver. The second, visual position constancy, is the (exocentric) stability of positions of objects relative to each other. We analyze the constancy of visual direction despite saccadic eye movements.Three information sources have been proposed to enable the visual system to achieve stability: the structure (...) of the visual field, proprioceptive inflow, and a copy of neural efference or outflow to the extraocular muscles. None of these sources by itself provides adequate information to achieve visual direction constancy; present evidence indicates that all three are used.Our final question concerns how information processing operations result in a stable world. The three traditionally suggested means have been elimination, translation, or evaluation. All are rejected. From a review of the physiological and psychological evidence we conclude that no subtraction, compensation, or evaluation need take place. The problem for which these solutions were developed turns out to be a false one. We propose a “calibration” solution: correct spatiotopic positions are calculated anew for each fixation. Inflow, outflow, and retinal sources are used in this calculation: saccadic suppression of displacement bridges the errors between these sources and the actual extent of movement. (shrink)

Ernst Mayr argued that the emergence of biology as a special science in the early nineteenth century was possible due to the demise of the mathematical model of science and its insistence on demonstrative knowledge. More recently, John Zammito has claimed that the rise of biology as a special science was due to a distinctive experimental, anti-metaphysical, anti-mathematical, and anti-rationalist strand of thought coming from outside of Germany. In this paper we argue that this narrative neglects the important role played (...) by the mathematical and axiomatic model of science in the emergence of biology as a special science. We show that several major actors involved in the emergence of biology as a science in Germany were working with an axiomatic conception of science that goes back at least to Aristotle and was popular in mid-eighteenth-century German academic circles due to its endorsement by Christian Wolff. More specifically, we show that at least two major contributors to the emergence of biology in Germany—Caspar Friedrich Wolff and Gottfried Reinhold Treviranus—sought to provide a conception of the new science of life that satisfies the criteria of a traditional axiomatic ideal of science. Both C.F. Wolff and Treviranus took over strong commitments to the axiomatic model of science from major philosophers of their time, Christian Wolff and Friedrich Wilhelm Joseph Schelling, respectively. The ideal of biology as an axiomatic science with specific biological fundamental concepts and principles thus played a role in the emergence of biology as a special science. (shrink)

This article informally presents a solution to the paradoxes of truth and shows how the solution solves classical paradoxes (such as the original Liar) as well as the paradoxes that were invented as counterarguments for various proposed solutions (“the revenge of the Liar”). This solution complements the classical procedure of determining the truth values of sentences by its own failure and, when the procedure fails, through an appropriate semantic shift allows us to express the failure in a classical two-valued language. (...) Formally speaking, the solution is a language with one meaning of symbols and two valuations of the truth values of sentences. The primary valuation is a classical valuation that is partial in the presence of the truth predicate. It enables us to determine the classical truth value of a sentence or leads to the failure of that determination. The language with the primary valuation is precisely the largest intrinsic fixed point of the strong Kleene three-valued semantics (LIFPSK3). The semantic shift that allows us to express the failure of the primary valuation is precisely the classical closure of LIFPSK3: it extends LIFPSK3 to a classical language in parts where LIFPSK3 is undetermined. Thus, this article provides an argumentation, which has not been present in contemporary debates so far, for the choice of LIFPSK3 and its classical closure as the right model for the truth predicate. In the end, an erroneous critique of Kripke-Feferman axiomatic theory of truth, which is present in contemporary literature, is pointed out. (shrink)

In this article we present a notion of “logical perfection”. We first describe through examples a notion of logical perfection extracted from the contemporary logical concept of categoricity. Categoricity (in power) has become in the past half century a main driver of ideas in model theory, both mathematically (stability theory may be regarded as a way of approximating categoricity) and philosophically. In the past two decades, categoricity notions have started to overlap with more classical notions of robustness and smoothness. These (...) have been crucial in various parts of mathematics since the nineteenth century. We postulate and present the category of logical perfection. We draw on various notions of perfection from mathematics of the 19th and 20th centuries and then trace the relation to the concept of categoricity in power as a logical notion of what a “mathematically perfect” structure is. (shrink)

Im 2009 erschienenen Buch "Philosophie des Leidens" versucht Boris Wandruszka, jene immanente Lebensstruktur und Lebensdynamik aufzudecken, die zu den einfachsten und fundamentalen Strukturmomenten des Leidens vorstosst; diese erste "Wissenschaft vom Leiden" transzendierte daher nicht die Grenzen der Anschaubarkeit, sondern verblieb in der "Immanenz des 'inneren Lebens' bzw. des Erlebens". Im aktuellen Buch "Metaphysik des Leidens" werden die "realen Bedingungen der Moglichkeit von Leiden" ermittelt: Wie muss eine Welt beschaffen sein, damit darin ein leidendes Wesen erscheinen konne? Welche Rolle hat (...) das Leiden in Bezug zum fundamentalen Widerfahrnis-, Resonanz- und Responsivitatscharakter des Lebens? Es wird gezeigt, dass menschliches Leben, das einer plural-agonalen Welt ausgesetzt ist, nicht leidfrei moglich ist, dass aber andererseits das Leid nicht das letzte Wort sein kann, sondern notwendig auf Ganzheit, Reifung, Erlosung und Harmonie bezogen ist. Nur auf dem Hintergrund der Spannung zwischen absoluter Seins-, Sinn- und Lebensfulle und der stets problematischen und fragilen Teilhabe von Menschen am "absoluten und leiduberwindenden Urleben" kann Leiden entstehen, durchlitten, verstanden, aber auch uberwunden werden. Hier erreicht der "Opfergedanke", in dem das unvermeidliche Leid frei angenommen und dadurch transformiert wird, seine reinste und hochste Ausformung. Erst nach Klarung dieser Verhaltnisse wird die "Theodizeefrage" als "das Problem der Probleme" angegangen und am Leitfaden der Hiob-Erzahlung diskutiert. Letztlich erweist sich, dass trotz allem Schmerz, Mangel, Unrecht und Unsinn ein "Potential des Unendlichen" im Leiden verborgen liegt, das auf seine Uberwindung durch Sein-, Sinn- und Werterfullung, durch Tat, Erkenntnis und Liebe verweist und dass diese drei "Machte" der Leidensherausforderung bedurfen, um ihre Weite, Tiefe und Hohe auszuloten. (shrink)

This volume sets out to address the question as to whether and how the critical conception of objectivity could still be relevant in contemporary philosophy. This means reflecting on the validity of the ascription of certaindefects to the Kantian system, as well as on their very description as defects. In order to do so, the volume brings together presentations that treat Kantian objectivity from many different angles. Some are more traditionally exegetical in nature, and discuss the interpretation of concepts within (...) or traits of Kant’s philosophy. Others trace the fate of the Kantian legacy in later philosophical and scientific thought. Still others reflect on the potential of transcendental perspectives for con-temporary philosophy and science. It is this variety in focus that makes the engagement with critical objectivity in this volume of interest not only to professional historians of philosophy and science, but to researchers engaged with the philosophical aspects of objectivity in their fields in general. (shrink)

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults from the DZNE-Longitudinal Cognitive Impairment and Dementia Study study. Participants reporting having played a musical instrument across three life periods were compared to controls without a history of musical instrument playing, well-matched for reserve proxies of education, (...) intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion. (shrink)

One of the great problems of caregivers and health professionals in recent times has been the so-called compassion fatigue and its association with burnout syndrome. Another pole of compassion has been described in terms of compassion satisfaction. Both propositions could be problematic in the caregiving setting. This is an analytical reflective article that through an apparent aporia tries to problematize and propose a theoretical synthesis that allows to denote compassion as a virtue in Aristotelian terms. To this end, it resorts (...) to etymologies, translations and mainly to the classical theoretical references regarding compassion fatigue, compassion satisfaction and, of course, Aristotelian ethics. This is a theoretical bet that leaves open the discussion regarding the dichotomies compassion fatigue and compassion satisfaction; apathy and hyperpathy; and proposes to rethink compassion as a virtue, a reasoned middle ground, contextualized in the framework of care between two possible excesses. (shrink)

Boris Kment takes a new approach to the study of modality that emphasises the origin of modal notions in everyday thought. He argues that the concepts of necessity and possibility originate in counterfactual reasoning, which allows us to investigate explanatory connections. Contrary to accepted views, explanation is more fundamental than modality.

The volume collects classics of Marxist historiography of science, including a new translation of Boris Hessen's “The Social and Economic Roots of Newton's ...

The paper is devoted to applications of algebraic logic to databases. In databases a query is represented by a formula of first order logic. The same query can be associated with different formulas. Thus, a query is a class of equivalent formulae: equivalence here being similar to that in the transition to the Lindenbaum-Tarski algebra. An algebra of queries is identified with the corresponding algebra of logic. An algebra of replies to the queries is also associated with algebraic logic. These (...) relations lie at the core of the applications.In this paper it is shown how the theory of Halmos (polyadic) algebras (a notion introduced by Halmos as a tool in the algebraization of the first order predicate calculus) is used to create the algebraic model of a relational data base. The model allows us, in particular, to solve the problem of databases equivalence as well as develop a formal algebraic definition of a database's state description. In this paper we use the term "state description" for the logical description of the model. This description is based on the notion of filters in Halmos algebras. When speaking of a state description, we mean the description of a function which realizes the symbols of relations as real relations in the given system of data. (shrink)

Commonly, a switch between networks mediating memory encoding and those mediating retrieval is observed. This may not only be due to differential involvement of neural resources due to distinct cognitive processes but could also reflect the formation of new memory traces and their dynamic change during consolidation. We used resting state fMRI to measure functional connectivity (FC) changes during post-encoding rest, hypothesizing that during this phase, new functional connections between encoding- and retrieval-related regions are created. Interfering and reminding tasks served (...) as experimental modulators to corroborate that the observed FC differences indeed reflect changes specific to post-encoding rest. The right inferior occipital and fusiform gyri (active during encoding) showed increased FC with the left inferior frontal gyrus and the left middle temporal gyrus (MTG) during post-encoding rest. Importantly, the left MTG subsequently also mediated successful retrieval. This finding might reflect the formation of functional connections between encoding- and retrieval-related regions during undisturbed post-encoding rest. These connections were vulnerable to experimental modulation: Cognitive interference disrupted FC changes during post-encoding rest resulting in poorer memory performance. The presentation of reminders also inhibited FC increases but without affecting memory performance. Our results contribute to a better understanding of the mechanisms by which post-encoding rest bridges the gap between encoding- and retrieval-related networks. (shrink)

BackgroundThe UN Convention on the Rights of Persons with Disabilities, and the reformed guardianship law in Germany, require that persons with a disability, including people with dementia in Alzheimer’s disease (PwAD), are supported in making self-determined decisions. This support is achieved through communication. While content-related communication is a deficit of PwAD, relational aspects of communication are a resource. Research in supported decision-making (SDM) has investigated the effectiveness of different content-related support strategies for PwAD but has only succeeded in improving understanding, (...) which, although one criterion of capacity to consent, is not sufficient to ensure overall capacity to consent. The aim of the ‘spatial intervention study’ of the DECIDE project is to examine an innovative resource-oriented SDM approach that focuses on relational aspects. We hypothesise that talking to PwAD in their familiar home setting (as opposed to a clinical setting) will reduce the complexity of the decision-making process and enhance overall capacity to consent. MethodsPeople with a suspected or confirmed diagnosis of dementia in Alzheimer’s disease will be recruited from two memory clinics (N = 80). We will use a randomised crossover design to investigate the intervention effect of the decision-making place on capacity to consent. Besides reasoning capacity, which is part of overall capacity to consent and will be the primary outcome, various secondary outcomes (e.g., other aspects of capacity to consent, subjective task complexity, decisional conflict) and suspected moderating or mediating variables (e.g., meaning of home, demographic characteristics) will be assessed.DiscussionThe results of the study will be used to develop a new SDM strategy that is based on relational resources for PwAD. If a change in location achieves the anticipated improvement in capacity to consent, future research should focus on implementing this SDM strategy in a cost-effective manner in clinical practice.Trial registration: DRKS00030799. (shrink)

There is a growing trend in European countries for childbearing to occur later in women’s lives. The recent increase in the use of ART, together with the long-term trend towards later childbearing, raises questions as to the acceptable age of childbearing in contemporary society. ART legislation varies considerably across Europe and age limits for access to fertility treatment are rarely defined. The legislation takes into account the preferences of potential parents; children’s preferences, however, are not ascertained. The article discusses a (...) research method used in a survey of older children and young adults. The objective of the survey was to answer the following questions: What age would children prefer their parents to be if they could choose? What are their reasons? Respondents were asked the following question: “How old would you like your mother and father to be when you are 20 (version for respondents younger than 16) or 25 (version for those older than 16) if you could wave a magic wand?” Furthermore, their reasons for wishing a change were identified through an open question, “Why would you like to change the age of your parents?”. (shrink)

In this handbook, I put into practice my philosophical views on children's mathematics. The handbook contains brief instructions and examples of mathematical activities. In the INSTRUCTIONS section, instructions are given on how, and in part why that way, to help preschool children in their mathematical development. In the ACTIVITIES section, there are examples of activities through which the child develops her mathematical abilities.

According to the aspect theory of instantiation, a particular A instantiates a universal B if and only if an aspect of A is cross-count identical with an aspect of B. This involves the assumption that both particulars and universals have aspects, and that aspects can mediate between different ways of counting things. I will ask what is new about this account of instantiation and, more importantly, whether it is an improvement on its older relatives. It will turn out that the (...) part of it that is new is the notion of cross-count identity among aspects. As I will show, this notion is both dubious and unnecessary. I will end by presenting a simplified aspect theory of instantiation that does not involve cross-count identity. (shrink)

I propose a general alethic theory of epistemic risk according to which the riskiness of an agent’s credence function encodes her relative sensitivity to different types of graded error. After motivating and mathematically developing this approach, I show that the epistemic risk function is a scaled reflection of expected inaccuracy. This duality between risk and information enables us to explore the relationship between attitudes to epistemic risk, the choice of scoring rules in epistemic utility theory, and the selection of priors (...) in Bayesian epistemology more generally. (shrink)

Starting from the idea that functions are formally similar to actions in that they are described and explained in a similar way, so that both admit of an accordion effect, I turn to Anscombe’s insight that the point of practical reasoning is to render explicit the relation between the different descriptions of an action generated by the accordion effect. The upshot is, roughly, that an item has a function if what it does can be accounted for by functional reasoning. Put (...) differently, a part of a system has a function if what it does is a functional part of what the system does. (shrink)

The aim of Modality and Explanatory Reasoning (MER) is to shed light on metaphysical necessity and the broader class of modal properties to which it belongs. This topic is approached with two goals: to develop a new and reductive analysis of modality, and to understand the purpose and origin of modal thought. I argue that a proper understanding of modality requires us to reconceptualize its relationship to causation and other forms of explanation such as grounding, a relation that connects metaphysically (...) fundamental facts to non-fundamental ones. While many philosophers have tried to give modal analyses of causation and explanation, often in counterfactual terms, I argue that we obtain a more plausible, explanatorily powerful and unified theory if we regard explanation as more fundamental than modality. The function of modal thought is to facilitate a common type of thought experiment – counterfactual reasoning – that allows us to investigate explanatory connections and which is closely related to the controlled experiments of empirical science. Necessity is defined in terms of explanation, and modal facts often reflect underlying facts about explanatory relationships. The study of modal facts is important for philosophy not because these facts are of much metaphysical interest in their own right, but largely because they provide evidence about explanatory connections. (shrink)

Analysing several characteristic mathematical models: natural and real numbers, Euclidean geometry, group theory, and set theory, I argue that a mathematical model in its final form is a junction of a set of axioms and an internal partial interpretation of the corresponding language. It follows from the analysis that (i) mathematical objects do not exist in the external world: they are our internally imagined objects, some of which, at least approximately, we can realize or represent; (ii) mathematical truths are not (...) truths about the external world but specifications (formulations) of mathematical conceptions; (iii) mathematics is first and foremost our imagined tool by which, with certain assumptions about its applicability, we explore nature and synthesize our rational cognition of it. (shrink)

While there are satisfactory answers to the question “How should we teach children mathematics?”, there are no satisfactory answers to the question “What mathematics should we teach children?”. This paper provides an answer to the last question for preschool children (early childhood), although the answer is also applicable to older children. This answer, together with an appropriate methodology on how to teach mathematics, gives a clear conception of the place of mathematics in the children’s world and our role in helping (...) children develop their mathematical abilities. Briefly, children’s mathematics consists of the world of children’s internal activities that they eventually purposefully organize in order to understand and control the outside world and organize their overall activities in it. We need to support a child in mathematical activities that she does spontaneously and in which she shows interest, and we need to teach her mathematics that she is interested in developing through these activities. In doing so, we must be fully aware that the child’s mathematics is part of the child’s world of internal activities and is not outside of it. We help the child develop mathematical abilities by developing them in the context of her world and not outside of it. From the point of view of this conception, the standards established today are limiting and too focused on numbers and geometric figures: these topics are too prominent and elaborated, and other mathematical contents are subordinated to them. Adhering to the standards, we drastically limit the mathematics of the child’s world, hamper the correct mathematical development of a child, and we can turn her away from mathematics. (shrink)