A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.Comment: 58 pages, 7 figures, 3 tables, pdf onl

When and Why Understanding Needs Phantasmata: A Moderate Interpretation of Aristotle’s De Memoria and De Anima on the Role of Images in Intellectual Activities

I examine the passages where Aristotle maintains that intellectual activity employs φαντάσματα (images) and argue that he requires awareness of the relevant images. This, together with Aristotle’s claims about the universality of understanding, gives us reason to reject the interpretation of Michael Wedin and Victor Caston, on which φαντάσματα serve as the material basis for thinking. I develop a new interpretation by unpacking the comparison Aristotle makes to the role of diagrams in doing geometry. In theoretical understanding of mathematical and natural beings, we usually need to employ appropriate φαντάσματα in order to grasp explanatory connections. Aristotle does not, however, commit himself to thinking that images are required for exercising all theoretical understanding. Understanding immaterial things, in particular, may not involve employing phantasmata. Thus the connection that Aristotle makes between images and understanding does not rule out the possibility that human intellectual activity could occur apart from the body

Fractals in the Nervous System: conceptual Implications for Theoretical Neuroscience

This essay is presented with two principal objectives in mind: first, to document the prevalence of fractals at all levels of the nervous system, giving credence to the notion of their functional relevance; and second, to draw attention to the as yet still unresolved issues of the detailed relationships among power law scaling, self-similarity, and self-organized criticality. As regards criticality, I will document that it has become a pivotal reference point in Neurodynamics. Furthermore, I will emphasize the not yet fully appreciated significance of allometric control processes. For dynamic fractals, I will assemble reasons for attributing to them the capacity to adapt task execution to contextual changes across a range of scales. The final Section consists of general reflections on the implications of the reviewed data, and identifies what appear to be issues of fundamental importance for future research in the rapidly evolving topic of this review

Apperceptive patterning: Artefaction, extensional beliefs and cognitive scaffolding

In “Psychopower and Ordinary Madness” my ambition, as it relates to Bernard Stiegler’s recent literature, was twofold: 1) critiquing Stiegler’s work on exosomatization and artefactual posthumanism—or, more specifically, nonhumanism—to problematize approaches to media archaeology that rely upon technical exteriorization; 2) challenging how Stiegler engages with Giuseppe Longo and Francis Bailly’s conception of negative entropy. These efforts were directed by a prevalent techno-cultural qualifier: the rise of Synthetic Intelligence (including neural nets, deep learning, predictive processing and Bayesian models of cognition). This paper continues this project but first directs a critical analytic lens at the Derridean practice of the ontologization of grammatization from which Stiegler emerges while also distinguishing how metalanguages operate in relation to object-oriented environmental interaction by way of inferentialism. Stalking continental (Kapp, Simondon, Leroi-Gourhan, etc.) and analytic traditions (e.g., Carnap, Chalmers, Clark, Sutton, Novaes, etc.), we move from artefacts to AI and Predictive Processing so as to link theories related to technicity with philosophy of mind. Simultaneously drawing forth Robert Brandom’s conceptualization of the roles that commitments play in retrospectively reconstructing the social experiences that lead to our endorsement(s) of norms, we compliment this account with Reza Negarestani’s deprivatized account of intelligence while analyzing the equipollent role between language and media (both digital and analog)

Distinct contributions of the fornix and inferior longitudinal fasciculus to episodic and semantic autobiographical memory

Autobiographical memory (AM) is multifaceted, incorporating the vivid retrieval of contextual detail (episodic AM), together with semantic knowledge that infuses meaning and coherence into past events (semantic AM). While neuropsychological evidence highlights a role for the hippocampus and anterior temporal lobe (ATL) in episodic and semantic AM, respectively, it is unclear whether these constitute dissociable large-scale AM networks. We used high angular resolution diffusion-weighted imaging and constrained spherical deconvolution-based tractography to assess white matter microstructure in 27 healthy young adult participants who were asked to recall past experiences using word cues. Inter-individual variation in the microstructure of the fornix (the main hippocampal input/output pathway) related to the amount of episodic, but not semantic, detail in AMs e independent of memory age. Conversely, microstructure of the inferior longitudinal fasciculus, linking occipitotemporal regions with ATL, correlated with semantic, but not episodic, AMs. Further, these significant correlations remained when controlling for hippocampal and ATL grey matter volume, respectively. This striking correlational double dissociation supports the view that distinct, large-scale distributed brain circuits underpin context and concepts in AM

Evaluation by magnetic resonance imaging of functional and structural connectivities of neurofunctional networks in mild Alzheimer's disease dementia and amnestic mild cognitive impairment subjects

Orientador: Márcio Luiz Figueredo BalthazarTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A demência por doença de Alzheimer (DA) é uma doença neurodegenerativa na qual ocorrem alterações cognitivas, neuropsiquiátricas e funcionais. Avanços recentes no estudo da neuroimagem na DA mostraram que as alterações presentes nesse grupo de pacientes não se restringem apenas às estruturas anatômicas particulares (tema abordado no ARTIGO 2), mas estendem-se também às redes neurofuncionais, as quais podem gerar problemas de memória e função executiva, entre outros. Devido às alterações estruturais apresentadas por atrofia, ao depósito de placas senis e emaranhados neurofibrilares, bem como à redução no metabolismo de glicose presente nas suas regiões, a Default Mode Network (DMN) tornou-se a rede neurofuncional de maior interesse no campo da DA. O principal objetivo desta Tese foi, dessa maneira, avaliar a conectividade de redes neurofuncionais na DA - enfatizando sobretudo na DMN, e suas relações com a cognição. Além disso, estudamos também outros aspectos anatômicos na DA - como alterações de substância branca e cinzenta no cérebro inteiro. No ARTIGO 1 mostramos que as alterações causadas pela doença afetam também áreas subcorticais como o tálamo e o corpo caloso, o que se relaciona com o déficit cognitivo dos pacientes. Em outro estudo com carácter mais exploratório (ARTIGO 6), mostramos que à medida em que a doença progrediu, as alterações na substância branca ocorreram de maneira mais extensa do que o esperado, levando em consideração as alterações estruturais encontradas na substância cinzenta. Assim, nossos dados sugerem que danos na substância branca possam ocorrer de maneira independente ao dano cortical. O ARTIGO 8, nesse contexto, traz um apanhado de resultados moleculares e de imagem que reforçam a hipótese de uma degeneração de redes neurofuncionais específicas em doenças neurodegenerativas, onde a propagação de proteínas alteradas ocorre ao longo dos tratos de substância branca (no caso da DA, em especial e primariamente nos tratos da DMN). Com isso em mente, no ARTIGO 4 tivemos como objetivo isolar apenas os tratos da DMN para avaliar o quão íntegro estruturalmente eles se apresentam na doença. De fato, observamos que pacientes com DA apresentam alterações microestruturais nos tratos da DMN, que contribuem para o déficit na performance cognitiva desses pacientes. No ARTIGO 5, investigamos não apenas a conectividade funcional das regiões da DMN, como também a média das amplitudes de baixa frequência (ALFF) do sinal BOLD dessas regiões. Encontramos que sujeitos com Comprometimento Cognitivo Leve amnéstico (CCLa, sujeitos sob risco de desenvolverem DA) por exemplo, possuem ALFF reduzido em regiões específicas da DMN, porém sem apresentar desconexão funcional entre elas. Pacientes com DA, entretanto, possuem não apenas ALFF reduzido em algumas regiões, mas também desconexão funcional entre elas. As amplitudes de ambos os grupos, entretanto, não possuem relação com o déficit cognitivo apresentado pelos pacientes; ao contrário da conectividade funcional dessas regiões. No ARTIGO 3, mostramos que outras redes neurofuncionais, como a de Linguagem e a de Controle Executivo também estão alteradas na DA. Em termos de correlatos neuropsicológicos apenas a conectividade da DMN mostrou relação com a performance em testes de memória episódica. No ARTIGO 7, por vez, tivemos como objetivo explorar outras hipóteses envolvendo a função da DMN. Nele, abordamos a questão da alteração do self nos pacientes com DA, e sugerimos uma relação com a atividade intrínseca do cérebro e o sentimento de auto-continuidade no tempoAbstract: Alzheimer¿s (AD) is a neurodegenerative disease that presents with cognitive, neuropsychiatric and functional alterations. Recent studies in the neuroimaging field of AD have shown that the alterations observed in these patients are not limited to specific anatomic structures (as shown in chapter 2) but also compromise neurofunctional networks, which can lead to memory and executive function impairment, among others. Due to the structural alterations such as atrophy, burden of amyloid beta and hyperphosphorilated tau, and metabolism reduction presented in its regions, the Default Mode Network (DMN) has become the most studied network in the AD field. Thus, the main objective of this thesis was to evaluate the functional and structural connectivities of the neurofunctional networks in AD ¿ emphasizing the DMN, and the relationship with cognition. Besides that, we have also studied some other anatomical aspects in AD, such as alterations in white and grey matter. In Chapter 1, we have shown that the alterations caused by the disease also affect subcortical areas such as the thalamus and the corpus callosum, which correlates to the cognitive deficit of the patients. In another exploratory study (Chapter 6), we observed that as the disease progressed, the alterations in white matter occurred were more extensive than expected, considering the structural alterations of the grey matter. Our results suggest that damage in white matter can occur independently of grey matter damage. In this context, Chapter 8 brings molecular and imaging results that reinforce the hypothesis that neurodegenerative diseases affect specific neurofunctional networks, and the propagation of altered proteins occur through white matter tracts (along DMN tracts). Keeping this in mind, in Chapter 4 we had as a main objective to isolate only the DMN tracts, in order to evaluate its structural connectivity in AD. Indeed, we observed that structural microalterations are present in DMN tracts of AD patients, contributing to their cognitive deficits. In Chapter 5, we not only investigated the functional connectivity of DMN regions, but also the amplitude of low frequency fluctuations (ALFF) of the blood oxygenation level signal of these regions. We found that amnestic mild cognitive impairment subjects (aMCI ¿ subjects at risk for developing AD) for instance, have decreased ALFF in specific regions of the DMN, though not presenting alterations in functional connectivity. AD patients, however, present both reduced ALFF and connectivity in the DMN regions. Interestingly, ALFF values did not correlate with the cognitive impairment of the patients; but connectivity values did. In Chapter 3, we have shown that other networks such as the Language and Executive Functions are also altered in AD. The functional connectivity of the DMN, in turn, correlated with episodic memory function. In Chapter 7, our main objective was to explore some other hypothesis involving the DMN function. Here, we mentioned the alterations in the self presented in AD patients and suggest a relationship with the brain intrinsic activity and the feeling of self continuity across timeDoutoradoCiencias BiomedicasDoutora em Ciências Médicas2013/10431-9FAPES

A dialogue of traditions on the reality of mind: Thomas Nagel and Bernard Lonergan

The scientific picture of the world is one of invisible particles and empty space, but this is not the world of our everyday experience. How can we reconcile the scientific view of the world with the view from our ordinary perspective? This thesis puts Thomas Nagel and Bernard Lonergan into dialogue on the question of the mind’s place in the world. Coming from different philosophical traditions, both thinkers provide a bigger picture in which to place materialism and to assess its errors. Thomas Nagel criticises modern forms of materialism because they try to explain away the reality of our perspective by reducing it to physical events in a perspectiveless scientific picture. He criticises the fundamental conception of the physical world upon which these reductionist theories depend, a conception that had its origins in the seventeenth century scientific revolution and one which conceived of the physical world as having no place for subjects’ perspectives. In Lonergan’s opinion, the reduction of the human consciousness to mere physical events is the result of a truncated conception of objectivity. The reason for this mistaken conception is that we confuse two distinct kinds of knowing, which in turn is because of a mistaken cognitional theory. This thesis argues that Nagel makes some insightful contributions to the place of mind in the cosmos, but that he, like the reductive materialists that he criticises, is limited by a truncated conception of objectivity that prevents him grasping the nature of the mind. This suggests that future philosophies of mind need to examine their presuppositions more deeply and be open to dialogue with one of the less well-known traditions of philosophy in contemporary scholarship – the Aristotelian-Thomistic tradition, in which Lonergan worked

Cortico-hippocampal activations for high entropy visual stimulus: an fMRI perspective

We perceive the environment around us in order to act upon it. To gain the desirable outcome effectively, we not only need the incoming information to be processed efficiently but we also need to know how reliable this information is. How this uncertainty is extracted from the visual input and how is it represented in the brain are still open questions. The hippocampus reacts to different measures of uncertainty. Because it is strongly connected to different cortical and subcortical regions, the hippocampus has the resources to communicate such information to other brain regions involved in visual processing and other cognitive processes. In this thesis, we investigate the aspects of uncertainty to which the hippocampus reacts. Is it the uncertainty in the ongoing recognition attempt of a temporally unfolding stimulus or is it the low-level spatiotemporal entropy? To answer this question, we used a dynamic visual stimulus with varying spatial and spatiotemporal entropy. We used well-structured virtual tunnel videos and the corresponding phase-scrambled videos with matching local luminance and contrast per frame. We also included pixel scrambled videos with high spatial and spatiotemporal entropy in our stimulus set. Brain responses (fMRI images) from the participants were recorded while they watched these videos and performed an engaging but cognitively independent task. Using the General Linear Model (GLM), we modeled the brain responses corresponding to different video types and found that the early visual cortex and the hippocampus had a stronger response to videos with higher spatiotemporal entropy. Using independent component analysis, we further investigated which underlying networks were recruited in processing high entropy visual information. We also discovered how these networks might influence each other. We found two cortico-hippocampal networks involved in processing our stimulus videos. While one of them represented a general primary visual processing network, the other was activated strongly by the high entropy videos and deactivated by the well-structured virtual tunnel videos. We also found a hierarchy in the processing stream with information flowing from less stimulus-specific to more stimulus-specific networks