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  1. Article ; Online: A theory of consciousness: computation, algorithm, and neurobiological realization.

    van Hateren, J H

    Biological cybernetics

    2019  Volume 113, Issue 4, Page(s) 357–372

    Abstract: The most enigmatic aspect of consciousness is the fact that it is felt, as a subjective sensation. The theory proposed here aims to explain this particular aspect. The theory encompasses both the computation that is presumably involved and the way in ... ...

    Abstract The most enigmatic aspect of consciousness is the fact that it is felt, as a subjective sensation. The theory proposed here aims to explain this particular aspect. The theory encompasses both the computation that is presumably involved and the way in which that computation may be realized in the brain's neurobiology. It is assumed that the brain makes an internal estimate of an individual's own evolutionary fitness, which can be shown to produce a special, distinct form of causation. Communicating components of the fitness estimate (either for external or for internal use) requires inverting them. Such inversion can be performed by the thalamocortical feedback loop in the mammalian brain, if that loop is operating in a switched, dual-stage mode. A first (nonconscious) stage produces forward estimates, whereas the second (conscious) stage inverts those estimates. It is argued that inversion produces another special, distinct form of causation, which is spatially localized and is plausibly sensed as the feeling of consciousness.
    MeSH term(s) Algorithms ; Brain/physiology ; Consciousness/physiology ; Humans ; Models, Neurological ; Neural Networks, Computer
    Language English
    Publishing date 2019-07-09
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 220699-7
    ISSN 1432-0770 ; 0340-1200
    ISSN (online) 1432-0770
    ISSN 0340-1200
    DOI 10.1007/s00422-019-00803-y
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  2. Article: A Unifying Theory of Biological Function.

    van Hateren, J H

    Biological theory

    2017  Volume 12, Issue 2, Page(s) 112–126

    Abstract: A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal ... ...

    Abstract A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism's fitness, and modulates the organism's variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories.
    Language English
    Publishing date 2017-03-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2209298-5
    ISSN 1555-5550 ; 1555-5542
    ISSN (online) 1555-5550
    ISSN 1555-5542
    DOI 10.1007/s13752-017-0261-y
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  3. Article: The Natural Emergence of (Bio)Semiosic Phenomena.

    van Hateren, J H

    Biosemiotics

    2015  Volume 8, Issue 3, Page(s) 403–419

    Abstract: Biological organisms appear to have agency, goals, and meaningful behaviour. One possibility is that this is mere appearance, where such properties are not real, but only 'as if' consequences of the physiological structure of organisms. Another ... ...

    Abstract Biological organisms appear to have agency, goals, and meaningful behaviour. One possibility is that this is mere appearance, where such properties are not real, but only 'as if' consequences of the physiological structure of organisms. Another possibility is that these properties are real, as emerging from the organism's structure and from how the organism interacts with its environment. Here I will discuss a recent theory showing that the latter position is most likely correct, and argue that the theory is largely consistent with the basics of the field of biosemiotics. The theory can be represented as a triad that resembles the semiotic triad proposed by Peirce, which connects a sign with its object through a process of interpretation. In the theory presented, the sign is an internalized version of fitness (i.e., expected reproductive rate) which refers to the true fitness through a feedback loop that in effect produces interpretation. The feedback loop entangles deterministic and stochastic forms of causation in such a way that genuine agency, goal-directedness, and their associated meaning emerge. It produces a strong form of emergence not reducible to its constituents. The result is that novel phenomena arise that are real and necessary components for a complete understanding of living organisms.
    Language English
    Publishing date 2015-05-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2438404-5
    ISSN 1875-1350 ; 1875-1342
    ISSN (online) 1875-1350
    ISSN 1875-1342
    DOI 10.1007/s12304-015-9241-4
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  4. Book ; Online: A theory of consciousness

    van Hateren, J. H.

    computation, algorithm, and neurobiological realization

    2018  

    Abstract: The most enigmatic aspect of consciousness is the fact that it is felt, as a subjective sensation. The theory proposed here aims to explain this particular aspect. The theory encompasses both the computation that is presumably involved and the way in ... ...

    Abstract The most enigmatic aspect of consciousness is the fact that it is felt, as a subjective sensation. The theory proposed here aims to explain this particular aspect. The theory encompasses both the computation that is presumably involved and the way in which that computation may be realized in the brain's neurobiology. It is assumed that the brain makes an internal estimate of an individual's own evolutionary fitness, which can be shown to produce a special, distinct form of causation. Communicating components of the fitness estimate (either for external or internal use) requires inverting them. Such inversion can be performed by the thalamocortical feedback loop in the mammalian brain, if that loop is operating in a switched, dual-stage mode. A first (nonconscious) stage produces forward estimates, whereas the second (conscious) stage inverts those estimates. It is argued that inversion produces another special, distinct form of causation, which is spatially localized and is plausibly sensed as the feeling of consciousness.

    Comment: minor revision, 21 pages, 10 figures, 1 table
    Keywords Quantitative Biology - Neurons and Cognition ; Computer Science - Artificial Intelligence
    Subject code 120
    Publishing date 2018-04-09
    Publishing country us
    Document type Book ; Online
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  5. Article ; Online: Active causation and the origin of meaning.

    van Hateren, J H

    Biological cybernetics

    2015  Volume 109, Issue 1, Page(s) 33–46

    Abstract: Purpose and meaning are necessary concepts for understanding mind and culture, but appear to be absent from the physical world and are not part of the explanatory framework of the natural sciences. Understanding how meaning (in the broad sense of the ... ...

    Abstract Purpose and meaning are necessary concepts for understanding mind and culture, but appear to be absent from the physical world and are not part of the explanatory framework of the natural sciences. Understanding how meaning (in the broad sense of the term) could arise from a physical world has proven to be a tough problem. The basic scheme of Darwinian evolution produces adaptations that only represent apparent ("as if") goals and meaning. Here I use evolutionary models to show that a slight, evolvable extension of the basic scheme is sufficient to produce genuine goals. The extension, targeted modulation of mutation rate, is known to be generally present in biological cells and gives rise to two phenomena that are absent from the non-living world: intrinsic meaning and the ability to initiate goal-directed chains of causation (active causation). The extended scheme accomplishes this by utilizing randomness modulated by a feedback loop that is itself regulated by evolutionary pressure. The mechanism can be extended to behavioural variability as well and thus shows how freedom of behaviour is possible. A further extension to communication suggests that the active exchange of intrinsic meaning between organisms may be the origin of consciousness, which in combination with active causation can provide a physical basis for the phenomenon of free will.
    MeSH term(s) Animals ; Biological Evolution ; Causality ; Computer Simulation ; Humans ; Models, Biological ; Time Factors
    Language English
    Publishing date 2015-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 220699-7
    ISSN 1432-0770 ; 0340-1200
    ISSN (online) 1432-0770
    ISSN 0340-1200
    DOI 10.1007/s00422-014-0622-6
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  6. Article ; Online: Extensive fitness and human cooperation.

    van Hateren, J H

    Theory in biosciences = Theorie in den Biowissenschaften

    2015  Volume 134, Issue 3-4, Page(s) 127–142

    Abstract: Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to ... ...

    Abstract Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to increase their fitness. The combined effect is known as inclusive fitness. Here it is argued that a further elaboration of fitness has evolved, particularly in humans. It is called extensive fitness and it incorporates producing organisms that are merely similar in phenotype. The evolvability of this mechanism is illustrated by computations on a simple model combining heredity and behaviour. Phenotypes are driven into the direction of high fitness through a mechanism that involves an internal estimate of fitness, implicitly made within the organism itself. This mechanism has recently been conjectured to be responsible for producing agency and goals. In the model, inclusive and extensive fitness are both implemented by letting fitness increase nonlinearly with the size of subpopulations of similar heredity (for the indirect part of inclusive fitness) and of similar phenotype (for the phenotypic part of extensive fitness). Populations implementing extensive fitness outcompete populations implementing mere inclusive fitness. This occurs because groups with similar phenotype tend to be larger than groups with similar heredity, and fitness increases more when groups are larger. Extensive fitness has two components, a direct component where individuals compete in inducing others to become like them and an indirect component where individuals cooperate and help others who are already similar to them.
    MeSH term(s) Biological Evolution ; Competitive Behavior ; Cooperative Behavior ; Genetic Fitness/genetics ; Genetics, Population ; Humans ; Models, Genetic
    Language English
    Publishing date 2015-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1376847-5
    ISSN 1611-7530 ; 1431-7613
    ISSN (online) 1611-7530
    ISSN 1431-7613
    DOI 10.1007/s12064-015-0214-6
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  7. Article ; Online: A new criterion for demarcating life from non-life.

    van Hateren, J H

    Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life

    2014  Volume 43, Issue 6, Page(s) 491–500

    Abstract: Criteria for demarcating life from non-life are important for deciding whether new candidate systems, either discovered extraterrestrially or constructed in the laboratory, are genuinely alive or not. They are also important for understanding the origin ... ...

    Abstract Criteria for demarcating life from non-life are important for deciding whether new candidate systems, either discovered extraterrestrially or constructed in the laboratory, are genuinely alive or not. They are also important for understanding the origin of life and its evolution. Current criteria are either too restrictive or too extensive. The new criterion proposed here poses that a system is living when it is capable of utilizing active causation, at evolutionary or behavioural timescales. Active causation is produced when the organism uses an estimate of its own Darwinian fitness to modulate the variance of stochasticity that drives hereditary or behavioural changes. The changes are subsequently fed back to the fitness estimate and used in the next cycle of a feedback loop. The ability to use a self-estimated fitness in this way is an evolved property of the organism, and the way in which fitness is estimated is therefore controlled and stabilized by Darwinian evolution. The hereditary and behavioural trajectories resulting from this mechanism combine predictability with unpredictability, and the mechanism produces a form of self-directed agency in living organisms that is absent from non-living systems.
    MeSH term(s) Biological Evolution ; Origin of Life
    Language English
    Publishing date 2014-01-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2018578-9
    ISSN 1573-0875 ; 0169-6149
    ISSN (online) 1573-0875
    ISSN 0169-6149
    DOI 10.1007/s11084-013-9352-3
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  8. Article ; Online: Validation of an LC-MS/MS assay for rapid and simultaneous quantification of 21 kinase inhibitors in human plasma and serum for therapeutic drug monitoring.

    Al Shirity, Zaid N / Westra, Niels / Hateren, Kai van / Munnink, Thijs H Oude / Kosterink, Jos G W / Mian, Paola / Hooge, Marjolijn N Lub-de / Touw, Daan J / Gareb, Bahez

    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

    2023  Volume 1229, Page(s) 123872

    Abstract: Kinase inhibitors have revolutionized cancer treatment in the past 25 years and currently form the cornerstone of many treatments. Due to the increasing evidence for therapeutic drug monitoring (TDM) of kinase inhibitors, the need is growing for new ... ...

    Abstract Kinase inhibitors have revolutionized cancer treatment in the past 25 years and currently form the cornerstone of many treatments. Due to the increasing evidence for therapeutic drug monitoring (TDM) of kinase inhibitors, the need is growing for new assays to rapidly evaluate kinase inhibitor plasma concentrations. In this study, we developed an LC-MS/MS assay for the rapid and simultaneous quantification of 21 kinase inhibitors. First, a literature search was conducted to ensure that the linear ranges of the analytes were in line with the reported therapeutic windows and/or TDM reference values. Subsequently, the assay was validated according to FDA and EMA guidelines for linearity, selectivity, carry-over, accuracy, precision, dilution integrity, matrix effect, recovery, and stability. The assay was fast, with a short run-time of 2 min per sample. Sample pre-treatment consisted of protein precipitation with methanol enriched with stable isotope-labeled internal standards (SIL-IS), and the mixture was vortexed and centrifuged before sample injection. Separation was achieved using a C18 column (3 μm,50 × 2.1 mm) with a gradient of two mobile phases (ammonium formate buffer pH 3.5 and acetonitrile). Analyte detection was conducted in positive ionization mode using selected reaction monitoring. The assay was accurate and precise in plasma as well as in serum. Extraction recovery ranged between 95.0% and 106.0%, and the matrix effect was 95.7%-105.2%. The stability of the analytes varied at room temperature and in refrigerated conditions. However, all drugs were found to be stable for 7 days in the autosampler. The clinical applicability of the analytical method (486 analyzed samples between 1 July 2022-1 July 2023) as well as external quality control testing results were evaluated. Taken together, the results demonstrate that the analytical method was validated and applicable for routine analyses in clinical practice.
    MeSH term(s) Humans ; Chromatography, Liquid/methods ; Drug Monitoring/methods ; Tandem Mass Spectrometry/methods ; Protein Kinase Inhibitors ; Reproducibility of Results ; Chromatography, High Pressure Liquid/methods
    Chemical Substances Protein Kinase Inhibitors
    Language English
    Publishing date 2023-09-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1180823-8
    ISSN 1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
    ISSN (online) 1873-376X
    ISSN 0378-4347 ; 1570-0232 ; 1387-2273
    DOI 10.1016/j.jchromb.2023.123872
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  9. Book ; Online: Extensive fitness and human cooperation

    van Hateren, J. H.

    2015  

    Abstract: Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to ... ...

    Abstract Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to increase their fitness. The combined effect is known as inclusive fitness. Here it is argued that a further elaboration of fitness has evolved, particularly in humans. It is called extensive fitness and it incorporates producing organisms that are merely similar in phenotype. The evolvability of this mechanism is illustrated by computations on a simple model combining heredity and behaviour. Phenotypes are driven into the direction of high fitness through a mechanism that involves an internal estimate of fitness, implicitly made within the organism itself. This mechanism has recently been conjectured to be responsible for producing agency and goals. In the model, inclusive and extensive fitness are both implemented by letting fitness increase nonlinearly with the size of subpopulations of similar heredity (for the indirect part of inclusive fitness) and of similar phenotype (for the phenotypic part of extensive fitness). Populations implementing extensive fitness outcompete populations implementing mere inclusive fitness. This occurs because groups with similar phenotype tend to be larger than groups with similar heredity, and fitness increases more when groups are larger. Extensive fitness has two components, a direct component where individuals compete in inducing others to become like them and an indirect component where individuals cooperate and help others who are already similar to them.

    Comment: Removed minor typo in axis Fig. 2a; 18 pages, 5 figures; in press
    Keywords Quantitative Biology - Populations and Evolution ; Quantitative Biology - Neurons and Cognition
    Subject code 612
    Publishing date 2015-03-16
    Publishing country us
    Document type Book ; Online
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  10. Article ; Online: Correction to: Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy.

    Spaans, Engelina / van Hateren, Kornelis J J / Groenier, Klaas H / Bilo, Henk J G / Kleefstra, Nanne / Brand, Paul L P

    European journal of pediatrics

    2019  Volume 178, Issue 4, Page(s) 605–606

    Abstract: The Abstract section and the in the Results sections of the original version of this article, unfortunately, contained errors. The correct data are now shown in this article. ...

    Abstract The Abstract section and the in the Results sections of the original version of this article, unfortunately, contained errors. The correct data are now shown in this article.
    Language English
    Publishing date 2019-01-25
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 194196-3
    ISSN 1432-1076 ; 0340-6199 ; 0943-9676
    ISSN (online) 1432-1076
    ISSN 0340-6199 ; 0943-9676
    DOI 10.1007/s00431-019-03325-8
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