Book Review: Emmanuel Alloa, Frank Chouraqui, and Rajiv Kaushik (eds.), Merleau-Ponty and Contemporary Philosophy (Albany: SUNY Press, 2019)

Merleau-Ponty and Contemporary Philosophy is an ambitious collected volume of fourteen chapters, accompanied by an epilogue by Jean-Luc Nancy, in which current Merleau-Ponty scholars together aim to demonstrate the urgent relevance of Merleau-Ponty to contemporary philosophy across a range of fields including ontology, epistemology, anthropology, embodiment, animality, politics, language, aesthetics, and art. Divided into four thematic sections, namely, “Legacies”, “Mind and Nature”, “Politics, Power, and Institution” and “Art and Aesthetics”, this collected volume provides a rich resource for Merleau-Ponty scholars who are interested in novel applications and understudied aspects of his thought. It also opens up Merleau-Ponty’s oeuvre to the general reader, presenting many possible entry-ways into the diversity of his work. In my review of Merleau-Ponty and Contemporary Philosophy, I suggest that each of its thematic sections could have been the subject of a separate volume themselves, and that the volume would then perhaps have not suffered from a number of poorly developed lines of argumentation. But I consider that the inclusion of all these thematically diverse sections in a single volume nonetheless presents a forceful display of the wide-ranging relevance of Merleau-Ponty’s work to contemporary philosophy

Equilibrium measures for two-sided shift spaces via dimension theory

Given a two-sided shift space on a finite alphabet and a continuous potential function, we give conditions under which an equilibrium measure can be described using a construction analogous to Hausdorff measure that goes back to the work of Bowen. This construction was previously applied to smooth uniformly and partially hyperbolic systems by the first author, Pesin, and Zelerowicz. Our results here apply to all subshifts of finite type and H\"older continuous potentials, but extend beyond this setting, and we also apply them to shift spaces with synchronizing words.Comment: 32 page

DSFworld: A flexible and precise tool to analyze differential scanning fluorimetry data.

Differential scanning fluorimetry (DSF) is a method to determine the apparent melting temperature (Tma) of a purified protein. In DSF, the raw unfolding curves from which Tma is calculated vary widely in shape and complexity. However, the tools available for calculating Tma are only compatible with the simplest of DSF curves, hindering many otherwise straightforward applications of the technology. To overcome this limitation, we designed new mathematical models for Tma calculation that accommodate common forms of variation in DSF curves, including the number of transitions, the presence of high initial signal, and temperature-dependent signal decay. When tested these models against DSFbase, an open-source database of 6235 raw, real-life DSF curves, these models outperformed the existing standard approaches of sigmoid fitting and maximum of the first derivative. To make these models accessible, we created an open-source software and website, DSFworld (https://gestwickilab.shinyapps.io/dsfworld/). In addition to these improved fitting capabilities, DSFworld also includes features that overcome the practical limitations of many analysis workflows, including automatic reformatting of raw data exported from common qPCR instruments, labeling of data based on experimental variables, and flexible interactive plotting. We hope that DSFworld will enable more streamlined and accurate calculation of Tma values for DSF experiments

Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide.

Resistance to chemotherapy substantially hinders successful glioblastoma (GBM) treatment, contributing to an almost 100% mortality rate. Resistance to the frontline chemotherapy, temozolomide (TMZ), arises from numerous signaling pathways that are deregulated in GBM, including Hedgehog (Hh) signaling. Here, we investigate suppression of Hh signaling as an adjuvant to TMZ using U87-MG and T98G cell lines as in vitro models of GBM. We found that silencing GLI1 with siRNA reduces cell metabolic activity by up to 30% in combination with TMZ and reduces multidrug efflux activity by 2.5-fold. Additionally, pharmacological GLI inhibition modulates nuclear p53 levels and decreases MGMT expression in combination with TMZ. While we surprisingly found that silencing GLI1 does not induce apoptosis in the absence of TMZ co-treatment, we discovered silencing GLI1 without TMZ co-treatment induces senescence as evidenced by a significant 2.3-fold increase in senescence associated β-galactosidase staining, and this occurs in a loss of PTEN-dependent manner. Finally, we show that GLI inhibition increases apoptosis in glioma stem-like cells by up to 6.8-fold in combination with TMZ, and this reduces the size and number of neurospheres grown from glioma stem-like cells. In aggregate, our data warrant the continued investigation of Hh pathway inhibitors as adjuvants to TMZ chemotherapy and highlight the importance of identifying signaling pathways that determine whether co-treatment will be successful

Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm

Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism’s ability to track and secure natural rewards. We examined the activity of individual nucleus accumbens (NAc) neurons during the performance of approach behaviors. Animals were presented with conditioned stimuli that were either positive (the CS+) or negative (the CS-) predictors of reward. Approach responses directed at these cues were recorded as lever presses and were significantly more likely to occur during CS+ presentations. On the test day, 75% of NAc neurons exhibited changes in firing rate (termed 'phasically active') during CS+ presentations. Of these cells, 47% were characterized by time-locked increases in cell firing while 53% showed reductions in firing for the duration of the CS+. The same cells typically showed little or no change during CS- presentations. These results suggest that NAc neurons encode reward prediction and/or approach responses elicited by reward-paired cues

Cellular and Chemical Dynamics Within the Nucleus Accumbens During Reward-related Learning and Decision Making

The ability to form and maintain associations between environmental cues, actions, and rewarding stimuli is an elementary yet fundamental aspect of learned behavior. Moreover, in order for organisms to optimize behavioral allocation after learning has occurred, such associations must be able to guide decision making processes as animals weigh the benefits and costs of potential actions. Multiple lines of research have identified that reward-related learning and decision making are mediated by a distributed network of brain nuclei that includes the nucleus accumbens (NAc) and its innervation from dopamine neurons located in the midbrain. However, the precise neural processing that underlies this function is unclear. The first set of experiments detailed in this dissertation took advantage of technological advances to characterize patterns of NAc dopamine release in real time, during behavioral performance. The results of the first experiment demonstrate for the first time that rapid dopamine release in the NAc is dramatically altered during stimulus-reward learning. Before learning, reward delivery produced robust increases in NAc dopamine concentration. After learning, these increases had completely transferred to the predictive cue and were no longer present when rewards were delivered. Further experiments revealed that cue-evoked increases in NAc dopamine concentration did not signal reward prediction alone, but reflected the work required to obtain rewards. Together, these results suggest that NAc dopamine encodes both the benefits and costs of predicted rewards. A second set of experiments used electrophysiological techniques to measure neural activity within the nucleus accumbens during decision making tasks. These experiments show that when rats were choosing between rewards with different effort requirements, a subset of NAc neurons tracked the degree of effort predicted by cues, while other neurons exhibited prolonged activation or inhibition as animals overcame large effort requirements to obtain rewards. Finally, when rats were choosing between rewards that came at different temporal delays, many NAc neurons exhibited changes in activity that correlated with reward delay. Such activity represents a candidate mechanism for linking actions with outcomes, and may also provide insight into the role of the NAc in psychiatric disorders characterized by maladaptive goal-directed behavior and decision making processes

Structural dynamic performance of longitudinal panel deck timber bridges

The primary objectives of the research presented here are to determine the dynamic response of longitudinal panel deck bridges to dynamic loads and to make design recommendations for dynamic allowance. Four bridges were field tested and bridge deflections and accelerations and vehicle accelerations were measured. The results of the field testing were used to meet the objectives of the study

Two Paths: A Critique of Husserl’s View of the Buddha

In “On the Teachings of Gotama Buddha” (1925) and “Socrates-Buddha” (1926), Edmund Husserl claims that the Buddha achieves a transcendental view of consciousness by performing the epoché. Yet, states Husserl, the Buddha fails to develop a purely theoretical and universal science of consciousness, i.e., phenomenology, because his purely practical goal of Nibbāna limits knowledge of consciousness. I evaluate Husserl’s claims by examining the Buddha’s Majjhima Nikāya. I argue that Husserl correctly identifies an epoché and transcendental viewpoint in the Buddha’s teachings. However, I contend that Husserl’s distinction between pure theory and pure praxis leads him to misconstrue the function of the Buddha’s epoché, the extent of knowledge that the Buddha gains from the transcendental viewpoint, and the nature of Nibbāna. I finally suggest that the Buddha presents a way of studying consciousness that is a way of life, meaning that any distinction between pure theory and pure praxis is dissolved

Nature Without the State: An Anarchist Critique of ‘Animalistic Evil’

I here present an anarchist critique of the idea of ‘animalistic evil’ and its common use as a justification for the State’s existence and use of force. On this view, ‘evil’ is a privation of morality, justice, and civilised behaviour. It is then identified with the ‘animalistic’ since animals are often thought to be defined by the aforesaid privation. I first clarify the idea of animalistic evil within the history of philosophy and science. Aristotle (384–322 BCE), Thomas Hobbes (1588–1679), and Thomas H. Huxley (1825–1895) prominently argue that all that prevents humanity from devolving into animalistic evil, a state of violent and individualistic struggle for bare survival, is the power of State government to forcibly control the animalistic drives within its citizens. I subsequently pose two questions. (1) Is it justified to associate animal life with evil when this is (a) understood as a privation of a morality, justice and society and (b) characterised as an individualistic struggle for survival? (2) If this is not justified, what is the political harm of doing so? Building on the work of the anarchist thinker Peter Kropotkin (1842–1921), I argue that any conception of animalistic evil is unjustifiable, that it is a false justification for the State’s existence and use of force, and that the State, upon making the empty threat of animalistic evil, both violently harms individuals and impedes the socially beneficial practice of mutual aid