Making a case for introspection

Defending first-person introspective access to own mental states, we argue against Carruthers' claim of mindreading being prior to meta-cognition and for a fundamental difference between how we understand our own and others' mental states. We conclude that a model based on one mechanism but involving two different kinds of access for self and other is sufficient and more consistent with the evidence

Blind Faith: Women at War in Khuda kay Liye and Escape from Taliban

Blind Faith: Women at War in Khuda kay Liye and Escape from TalibanInspired by Huntingdon’s “Clash of Civilizations,†George W. Bush’s Manichean cold war rhetoric struck a responsive chord in the media, with the villification of Islam or more precisely the conflation of Islam – as though it was a monolithic religion – with terrorism. For Hollywood and Bollywood, the Islamic terrorist became the archetypal villain and a new subgenre of thrillers emerged featuring terrorist cells with films such as Shoot on Sight: Is it a crime to be a Muslim? (Mundhra, 2007), New York (Khan, 2009) or My Name is Khan (Johar, 2010). Those binaries also underpin films about Pakistani and Afghan societies. The present paper discusses the issues of women’s rights, particularly forced marriage, and the growing influence of fundamentalism in the Pakistani box office success, Khuda kay Liye (Mansoor, 2007) and in the Bollywood film, Escape from Taliban (Chatterjee, 2003)

BUILDING TOOLS FOR IMPROVED MODULATION OF THE HUMAN GABAA RECEPTOR, A CENTRAL NERVOUS SYSTEM TARGET FOR THE TREATMENT OF ANXIETY

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market. The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABAA receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABAA receptor interaction suggests that constraining the isobutenyl group relative to the 5,6 membered ring system of VA could improve its binding specificity and affinity to the GABAA receptor. In planta, valerena-1,10-diene (VLD) is synthesized from farnesyl pyrophosphate (FPP) valerenadiene synthase (VDS), a sesquiterpene synthase. VLD is then carboxylated at one of its isobutenyl terminal methyl groups to yield VA. Our first objective was to engineer the VDS enzyme for altered product specificity and a more chemically constrained VLD scaffold. Using computational homology modelling and phylogenetic sequence analysis of characterized sesquiterpene synthases, amino acid residues in or near the active site and potentially impinging on catalytic specificity of VDS were identified. Residues were mutated via site-directed mutagenesis and mutants evaluated in vivo and in vitro. While wild type VDS’ products were 66 % VLD, 5 % allo-aromadendrene, and 29 % bicyclogermacrene (BCG), mutant Y535F yielded solely BCG. VDS with alanine or serine substituted for asparagine at position 455 lost all its ability to produce any of the wild type products and instead yielded a suite of seven new products dominated by germacrene-D-ol (≥ 40 %). To install a carboxylic acid functional group onto the sesquiterpene hydrocarbon scaffolds, we focused on the development of a host platform harboring an endomembrane system suitable for the expression of eukaryotic cytochrome P450 enzymes (P450s). As an example, plasmid co-expression of VDS, Lactuca sativa germacrene-A oxidase, and Artemisia annua cytochrome P450 oxidoreductase yielded an average 2mg/L of VA. For biological evaluation of sesquiterpene analogs, HEK293 cells transiently transfected with the human GABAA receptor subunit genes ⍺1, β3, and 2L, as well as a HEK293 cell line stably expressing the same GABA subunit genes, were optimized for sensing changes in membrane potential using a fluorescent bioassay. Effective concentration of test compounds and absolute magnitude of membrane depolarization in the transiently transfected cells gave the greatest responsiveness as determined for -aminobutyric acid (EC50 = 808 ± 206 nM, Emax = 13,309 ± 953 AFU’s), clonazepam (EC50 = 15 ± 8 nM, Emax = 4,211 ± 334 AFU’s), and VA (EC50 = 2,397 ± 341 nM, Emax = 5,935 ± 104 AFU’s). Abscisic acid, gibberellic acid, and cyclopartheniol demonstrated little to no detectable activity for modulating the human GABAA receptor

A Letter to a Struggling German Catholic During the Reformation

The assignment presented was to write a position paper in the format of a letter to a German Catholic friend undergoing an existential crisis during the Reformation period. First, we needed to analyze Martin Luther\u27s 3 Walls of the Romanists, and then take a stance either choosing to follow or ignore Luther. In writing this essay, I spent a lot of time reading over Luther\u27s arguments and reflecting on my own personal views and compared them with careful consideration. I was aware that the situation at the time was a matter of life and death for many, and attempted to reflect that urgency and consideration during my analysis and while presenting my stance

To widen the circle: a grounded theory study of couples co-creating transformation

The researcher studied the process of transformation among 16 married and cohabiting couples. Research focused upon co-created transformation, a profound change in lifestyle and relationship stemming from a collaborative effort to (1) address incongruities between a couples\u27 lifestyle and mutually held values, and (2) enhance their mutual fulfillment and quality of life.;After focusing the research upon four exemplary couples, a four-stage model of co-created transformation emerged. The four stages include (1) acknowledging incongruity, (2) generating preferences, (3) widening the circle, and (4) continuing the journey. The model is founded upon three necessary conditions, which include (1) basic needs, (2) relational resources, and (3) intellectual resources. Alternate case analysis is included. Co-created transformation is compared with another stage model, the transtheoretical model of change. Comparison serves in part to validate the model of co-created transformation and raises questions for further research.;The model of co-created transformation is a substantive level theory that merits further investigation. It is anticipated that the model may assist couples contemplating transformation, human service professionals guiding a transformation, and scholars investigating change. Given the aging and upcoming retirement of baby-boomers, this model is timely as members of this demographic group begin to consider their next steps in life