296 research outputs found

    Presentism and the flow of time

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    The paper examines the relations between presentism and the thesis concerning the existence of the flow of time. It tries to show that the presentist has to admit the existence of the passage of time and that the standard formulation of presentism as a singular thesis saying that only the present exists is insufficient because it does not allow the inference of the existence of the passage of time. Instead of this, the paper proposes a formulation of presentism with the aid of the notion of becoming; not only does a formulation state the existence of the flow of time in such a way as to avoid the question of the rate of the passage of time, it also allows the inference of the existence of only present things and events. The paper demonstrates that the proposed conception of presentism also has other virtues, such as homogeneity, non-triviality, and ability to express dynamicity of presentists’ image of the world which testify for it

    Being, Becoming and the Undivided Universe: A Dialogue between Relational Blockworld and the Implicate Order Concerning the Unification of Relativity and Quantum Theory

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    In this paper two different approaches to unification will be compared, Relational Blockworld (RBW) and Hiley's implicate order. Both approaches are monistic in that they attempt to derive matter and spacetime geometry 'at once' in an interdependent and background independent fashion from something underneath both quantum theory and relativity. Hiley's monism resides in the implicate order via Clifford algebras and is based on process as fundamental while RBW's monism resides in spacetimematter via path integrals over graphs whereby space, time and matter are co-constructed per a global constraint equation. RBW's monism therefore resides in being (relational blockworld) while that of Hiley's resides in becoming (elementary processes). Regarding the derivation of quantum theory and relativity, the promises and pitfalls of both approaches will be elaborated. Finally, special attention will be paid as to how Hiley's process account might avoid the blockworld implications of relativity and the frozen time problem of canonical quantum gravity.Comment: 33 pages, 7 figures. Revised to include modified Regge calculus results. Accepted for publication in Foundations of Physics. arXiv admin note: substantial text overlap with arXiv:1106.333

    Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

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    Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

    Presentism remains

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    Here I examine some recent attempts to provide a new way of thinking about the philosophy of time that question the central role of ‘presentness’ within the definition of presentism. The central concern raised by these critics turns on the intelligibility and theoretical usefulness of the term ‘is present’ (cf. Correia and Rosenkrantz in Thought 4:19–27, 2015; Deasy in Nous, 2017. https://doi.org/10.1111/nous.12109; Williamson in Modal logic as metaphysics, OUP, Oxford, 2013). My overarching aim is to at least challenge such concerns. I begin with arguments due to Deasy (Nous, 2017. https://doi.org/10.1111/nous.12109). Deasy develops a view that he calls ‘transientism’ and that he takes to be a well-motivated version of presentism. I show that both this way of thinking about presentism and the argument supposedly motivating it all fail. I then move to an argument due to Correia and Rosenkrantz (Thought 4:19–27, 2015). Correia and Rosenkrantz purport to show that presentism can be salvaged without making recourse to the term ‘is present’. I demonstrate that their arguments fail. I then move on to a view, proposed and defended by Merricks (Truth and ontology, OUP, Oxford, 2007), Tallant (Erkenntnis 79:479–501, 2014), and Zimmerman (Philos Pap 25:115–126, 1996), and show that it has the wherewithal to meet the challenges raised by Williamson (Modal logic as metaphysics, OUP, Oxford, 2013) who, as noted above, raises genuine concerns about our capacity to define presentism

    Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease.

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    Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases

    An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

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    BACKGROUND & AIMS: The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. METHODS & RESULTS: Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. CONCLUSION: These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases

    Generation of a Convalescent Model of Virulent Francisella tularensis Infection for Assessment of Host Requirements for Survival of Tularemia

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    Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR+ cells, γδTCR+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4+ and CD8+ cells are the primary producers of IFN-γand that γδTCR+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection
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