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Multiscale Dynamics: from single neurons to large-scale networks Modeling and applications with a focus on Alzheimer’s Disease
No full textUnderstanding the brain's function and pathology necessitates a multiscale approach, asneurological disorders stem from disruptions at the cellular level that cascade to alterlarge-scale network dynamics. This thesis integrates computational modeling across microand macroscales to investigate neural dynamics in both health and disease, with a core focuson Alzheimer's disease (AD). The work is organized into three complementary studies. First, we investigated the cellular mechanisms underlying the formation of hippocampal Place Cells (PCs). We developed a morphologically and biophysically realistic computational model of a CA1 pyramidal neuron to examine how it acquires spatially selective firing. The model demonstrates that place-field emergence results from the coordinated activation of two different inputs: a distal input from the entorhinal cortex (EC) and a proximal input from the CA3. This co-activation selectively potentiates specific synapses, leading the neuron to codefor a cue location. The model reproduces key experimental observations, including place-field stability across trajectories, stability after environment rotation, and place-field remapping. To date, it represents the only cellular model that mechanistically explains PC formation with biophysical and morphological accuracy, suggesting a potential mechanismthrough which early hippocampal impairment in AD could disrupt spatial navigation. Next, we studied Alzheimer’s disease (AD) at the macroscale using source-reconstructed EEG from 28 patients and 29 healthy controls. We quantified brain fluidity, a measure of the brain’s ability to flexibly reconfigure functional connectivity over time. AD patients showed frequency-specific disruptions: fluidity increased in the theta band but decreased in the beta band. Reduced beta-fluidity significantly correlated with higher cerebrospinal tau levels andpredicted cognitive performance better than standard biochemical markers, indicating that loss of temporal flexibility is a signature of AD-related network disconnection. Finally, we examined multiple sclerosis (MS). In 38 participants (18 MS and 20 controls), we combined MEG resting-state activity with MRI tractography and used large-scale brain models to estimate how tract lesions translate into conduction delays. Each brain region was modeled as a Stuart–Landau oscillator coupled by subject-specific connectomes. Through Bayesian model inversion, we showed that the inferred lesion–delay parameter stronglycorrelates with individual alpha-peak slowing in MEG and predicts clinical disability, whereas total lesion volume alone does not. This provides the first tract-specific quantitativemapping between myelin damage and functional slowing. Across these three studies, the thesis demonstrates how cellular alterations, loss of functional flexibility, and structural disconnection impair the timing and integration of neural information. The results provide a framework for the development of mechanistic biomarkersand suggest that multiscale models could contribute to individualized predictions of disease progression and therapeutic responses.Understanding the brain's function and pathology necessitates a multiscale approach, asneurological disorders stem from disruptions at the cellular level that cascade to alterlarge-scale network dynamics. This thesis integrates computational modeling across microand macroscales to investigate neural dynamics in both health and disease, with a core focuson Alzheimer's disease (AD). The work is organized into three complementary studies. First, we investigated the cellular mechanisms underlying the formation of hippocampal Place Cells (PCs). We developed a morphologically and biophysically realistic computational model of a CA1 pyramidal neuron to examine how it acquires spatially selective firing. The model demonstrates that place-field emergence results from the coordinated activation of two different inputs: a distal input from the entorhinal cortex (EC) and a proximal input from the CA3. This co-activation selectively potentiates specific synapses, leading the neuron to codefor a cue location. The model reproduces key experimental observations, including place-field stability across trajectories, stability after environment rotation, and place-field remapping. To date, it represents the only cellular model that mechanistically explains PC formation with biophysical and morphological accuracy, suggesting a potential mechanismthrough which early hippocampal impairment in AD could disrupt spatial navigation. Next, we studied Alzheimer’s disease (AD) at the macroscale using source-reconstructed EEG from 28 patients and 29 healthy controls. We quantified brain fluidity, a measure of the brain’s ability to flexibly reconfigure functional connectivity over time. AD patients showed frequency-specific disruptions: fluidity increased in the theta band but decreased in the beta band. Reduced beta-fluidity significantly correlated with higher cerebrospinal tau levels andpredicted cognitive performance better than standard biochemical markers, indicating that loss of temporal flexibility is a signature of AD-related network disconnection. Finally, we examined multiple sclerosis (MS). In 38 participants (18 MS and 20 controls), we combined MEG resting-state activity with MRI tractography and used large-scale brain models to estimate how tract lesions translate into conduction delays. Each brain region was modeled as a Stuart–Landau oscillator coupled by subject-specific connectomes. Through Bayesian model inversion, we showed that the inferred lesion–delay parameter stronglycorrelates with individual alpha-peak slowing in MEG and predicts clinical disability, whereas total lesion volume alone does not. This provides the first tract-specific quantitativemapping between myelin damage and functional slowing. Across these three studies, the thesis demonstrates how cellular alterations, loss of functional flexibility, and structural disconnection impair the timing and integration of neural information. The results provide a framework for the development of mechanistic biomarkersand suggest that multiscale models could contribute to individualized predictions of disease progression and therapeutic responses
Migration climatique : mesurer l’immesurable ?
No full textThis paper considers climate migration not as an object of measurement or quantification, but as a semiotic and political apparatus through which climate change becomes tangible and interpretable in the public sphere. The figure of the climate migrant thus functions as a discursive mediator, translating the effects of climate change into accessible narratives and social and political stakes. By examining how media representations construct this figure across different scales – from local micro narratives to global macro-narratives – the paper demonstrates that numbers and statistics do not merely represent the phenomenon; rather, they actively contribute to shaping its perception by modulating attention, affective responses, and collective interpretation. Drawing on the work of Bruno Latour, the analysis proposes a rethinking of the relationship between narration, truth effects, and political action from the perspective of the “Terrestrial,” understood not as a natural backdrop but as an emerging political actor within the public sphere
Unified a-priori estimates for minimizers under p,q-growth and exponential growth
No full textWe propose some general growth conditions on the function , including the so-called natural growth,
or polynomial, or growth conditions, or even exponential growth, in order to obtain that any local minimizer of the
energy integral \ is locally Lipschitz continuous in . In fact this is the fundamental
step for further regularity: the local boundedness of the gradient
of any Lipschitz continuous local minimizer a-posteriori makes
irrelevant the behavior of the integrand as ; i.e., the general
growth conditions a posteriori are reduced to a standard growth, with the
possibility to apply the classical regularity theory. In other words, we
reduce some classes of non-uniform elliptic variational problems to
a context of uniform ellipticity
The TRiC/CCT Complex at the Crossroads of Metabolism and Hypoxia in GBM: Implications for IDH-Dependent Therapeutic Targeting
No full textGlioblastoma (GBM) is characterized by its unique molecular features, such as self-renewal and tumorigenicity of glioma stem cells that promote resistance, largely resulting in treatment failure. Among the molecular alterations significant to GBM biology and treatment, mutations in isocitrate dehydrogenase (IDH) have assumed particular relevance. IDH-mutant and IDH-wild-type tumors exhibit significantly different metabolic characteristics, clinical behavior, and therapeutic sensitivities, making IDH status a critical determinant in determining prognosis and treatment strategies for GBM. In the context of cancer, chaperones were shown to promote tumor progression by supporting malignant cells over healthy ones. While heat shock proteins (HSPs) have long been implicated in the molecular mechanisms of tumor phenotype progression, recent attention has turned to CCT (chaperonin containing TCP1), orchestrating proteostasis. The chaperonin CCT is being explored as a diagnostic and therapeutic target in many cancers, including GBM, owing to its involvement in key oncogenic signaling pathways such as Wnt, VEGF, EGFR, and PI3K/AKT/mTOR. However, its role in the GBM-tricarboxylic acid (TCA) cycle cascade is still not well understood. Therefore, the present review highlights the potential role of the CCT complex in regulating hypoxia-inducible factor (HIF) activation by modulating enzymes responsive to metabolites derived from glucose metabolism and the TCA cycle in a manner dependent on oxygen availability and IDH mutation status
THE OBLIGATIONS OF STATES AND NON-STATE ACTORS IN RELATION TO MULTINATIONAL CORPORATIONS UNDER DOMESTIC AND INTERNATIONAL LAW: A CASE STUDY ON THE LEGAL REGIMES COVERING CORPORATIONS IN THE EXTRACTIVE INDUSTRIES IN SIERRA LEONE AND ITALY
No full textA leverage point perspective for policymaking for circular transition - A case study of the Icelandic building industry
No full textAchieving the UN Sustainable Development Goals requires systemic transformation through policy reforms that enable a socio-technical transition. This study examines the Icelandic building industry, a sector of significant environmental impact that has recently published a roadmap for sustainable development. Through a case study, the research evaluates the roadmap ́s transformative potential through stakeholder-driven policy formulation. The study compares the transformative potential of the roadmap's interventions with those formulated using Meadows' (1999) leverage-point framework during the agenda-setting phase (TLP framework). Its findings show that the roadmap interventions do not sufficiently address the deep leverage points required for industry-wide transition. In contrast, applying the TLP framework during agenda-setting enhances the transformative potential of proposed interventions, supporting a shift toward a circular economy. This study contributes to transition studies by applying the multi-level perspective and circular economy lens to reveal the lack of transformative policies in Iceland's building industry roadmap. It demonstrates how the TLP framework can assess policy documents, inform agenda-setting, and enhance the transformative potential of interventions. The findings provide actionable guidance for policymakers in Iceland, including developing a shared circular economy vision, shifting business attitudes, and embedding circular principles into design, infrastructure, planning, and professional training. The findings may extend beyond the Icelandic context, requiring further research to test transferability
Invisible near-infrared luminescent marker incorporating Egyptian blue in halloysite-based geopolymer mortars: Applications in covert tagging
No full textEgyptian blue (EB), a calcium copper tetrasilicate known since antiquity as a pigment for its intense blue color, has been incorporated in minimal concentrations into halloysite clay-based geopolymeric mortars for use in covert optical tagging applications. The geopolymer matrix (GP) has been synthesized through alkaline activation of halloysite using 12 M sodium hydroxide, with EB added at variable concentration (0.2-0.4-0.6 wt%) with respect to the clay. Structural and thermal analyses (XRD, FTIR, TGA) have confirmed the successful geopolymerization and chemical stability of EB under highly alkaline conditions. Optical characterization via visible-induced luminescence (VIL) imaging and luminescence spectroscopy revealed that, despite the visually undetectable quantities, the embedded EB has retained its luminescent properties, emitting in the NIR range when excited in the red-visible region. Solid-state 27Al and 29Si NMR analyses have evidenced a reorganization a structural reorganization of the aluminosilicate framework upon EB incorporation, consistent with specific interactions between the pigment and the geopolymer network. A functional QR code has been successfully fabricated by stenciling GP_EB_0.6 mortar onto a GP background. Concealed under normal lighting and revealed via VIL imaging, the code granted access to a digital file with material specifications and synthesis protocols, demonstrating the system's potential as a covert, digitally retrievable tagging approach for secure applications
Dal lavoro al progetto. L'architetto nella Grecia antica e oltre
No full textL'articolo presenta in modo divulgativo il ruolo dell'architetto (architekton) nel mondo greco-romano, soffermandosi sulle sue funzioni sociali, sul valore epistemologico del suo mestiere e sull'affermarsi dell'architetto dal V sec. a.C. in poi come una figura di artigiano versato in diverse discipline, cui già il pensiero filosofico greco attribuisce il ruolo di poliedrico capocantiere e di guida degli altri operai impegnati nella finalizzata realizzazione di un'opera. In possesso di perizia manuale così come di ingegno creativo, l'architetto si caratterizza sempre di più, grazie all'immagine offerta dal De architectura di Vitruvio, per il suo sapere enciclopedico, ma anche per la sua capacità risolutiva di intrecci complessi, che ne fanno uno dei protagonisti anche della scena comica del teatro greco e latino. Sulla scia del prestigio culturale acquisito con il recupero del manuale vitruviano, l'architetto assurge, dall'Umanesimo in poi, a figura cardine della progettazione, diventa letterato e intellettuale, sodale del potere e illuminato visionario, capace di immaginare la città del futuro
Venture capital decision-making in green investments
No full textThe overarching purpose of this thesis is to provide a comprehensive understanding of venture capital decision-making in the context of green startups. To address this purpose, the present work examines three issues regarding: 1) the propensity of heterogenous VC types (Independent, Corporate, and Governmental) towards green startups, 2) the influence of environmental policy on the decision-making of Independent and Corporate VCs, and 3) the role of similarity-heuristics, with a specific focus on value similarity on Independent VCs’ decisions to invest in green startups. These three issues have been investigated in two research articles that provide a basis for this doctoral thesis. This thesis is organized into five chapters. Chapter 1 introduces green startups and green VC investments, outlining the thesis structure, objectives, and methods. Chapter 2 reviews key definitions and prior literature, identifies three research gaps, and presents the theoretical perspectives used. Chapter 3 analyzes how IVC, CVC, and GVC make investment decisions in green startups and examines how environmental policies incentivize or constrain independent and corporate VCs. Chapter 4 explores heuristics in green investing, focusing on founder–VC similarity (especially value similarity) in IVC decisions. Chapter 5 summarizes findings, highlights theoretical contributions, discusses implications for founders, policymakers, and investors, and concludes with limitations and future research directions
