Nietzsche: A Response to Kant's Sundering of the World

Thesis advisor: Vanessa P. RumbleFriedrich Nietzsche is one of the most revolutionary and influential philosophers of post-Romantic Germany. He called into question ancient habits of mind and ingrained moral prejudices prevalent in European culture since the rise of Christendom. The intellectual and popular communities, in Germany and Europe at large, primarily disregarded Nietzsche's work until after his death. However, contemporary continental thinkers have been greatly influenced by Nietzsche and his provocative rhetoric. Nietzsche's work is particularly remarkable in light of his upbringing and childhood experiences. The scion of a long line of Lutheran ministers, Nietzsche mounted a critique of traditional piety and religious institutions that was unprecedented in its force and insight. Nietzsche came from an intellectual family and was inspired by the considerable efforts of earlier German thinkers. In general, the development and articulation of any philosopher's ideas are dependent on the environment in which he or she exists. For this reason, and to gain a better understanding of Nietzsche's personality, this study will place great emphasis on the biographical information pertaining to both Nietzsche and other German thinkers who influenced him. It is impossible to fully understand the position and concerns of philosophers like Nietzsche and Kant without first delving into their childhood and education. In the case of Nietzsche, a whole tradition of German intellectualism affected his view of the world and the ideas that he adopted and later reshaped into a penetrating examination of the foundations of Western European culture.Thesis (BA) — Boston College, 2003.Submitted to: Boston College. College of Arts and Sciences.Discipline: Philosophy.Discipline: College Honors Program

A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease

BackgroundDiffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor.MethodsWe used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation.ResultsMice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation.ConclusionIn a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control

Comprehensive assessment of blood–brain barrier opening and sterile inflammatory response: unraveling the therapeutic window

Abstract Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood–brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI). High-resolution MRI-guided FUS was employed in mouse brains to assess BBBO by manipulating these two parameters. Afterward, the sterile inflammatory response (SIR) was studied 6 h post-FUS treatment. Results demonstrated that both MVD and MI significantly influenced the extent of BBBO, with higher MVD and MI leading to increased permeability. Moreover, RNA sequencing revealed upregulation of major inflammatory pathways and immune cell infiltration after BBBO, indicating the presence and extent of SIR. Gene set enrichment analysis identified 12 gene sets associated with inflammatory responses that were significantly upregulated at higher MVD or MI. A therapeutic window was established between therapeutically relevant BBBO and the onset of SIR, providing operating regimes to avoid damage from stimulation of the NFκB pathway via TNFɑ signaling to apoptosis. These results contribute to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and further elucidate the underlying molecular mechanisms driving sterile inflammation