Making Meaning Manifest

In recent work Sperber and Wilson expand on ideas initially presented in Relevance (1986) and flesh out continuua between showing and meaning, and determinate and indeterminate content. Drawing on Sperber and Wilson’s work, and at points defending it from what I see as potential objections, I present a Schema of Communicative Acts (SCA) that includes an additional third continuum between linguistic and non-linguistic content. The SCA clears the way for consideration of what exactly is meant by showing, the motivations of speakers, how affect impacts expression, and metaphor. The SCA allows us to consider not only how but why we engage in certain forms of communicative behavior, and captures the incredible nuance of human interactions: said and meant, linguistic and non-linguistic, determinate and indeterminate

Cooperation with Multiple Audiences

Steven Pinker proposes a game-theoretic framework to help explain the use of veiled speech in contexts where the ultimate aims of the speaker and hearer may diverge—such as cases of bribing a police officer to get out of a ticket and paying a maître d’ to get a table. This is presented as a response to what Pinker sees as the failure in H. P. Grice’s influential theory of meaning to recognize that speakers and hearers are not always cooperating. In this paper I argue that Pinker mischaracterizes Grice’s views on cooperation, and use this to refi ne a positive picture of what sort of cooperation is demanded by Grice’s Cooperative Principle. This positive picture serves to insulate the Gricean framework from objectors—including Pinker—who overstate the obligations entailed by the adoption of the Cooperative Principle. I then argue that the cases Pinker presents are best treated by recognizing that in each instance the utterance is formulated with two intentions towards two different audiences and detail a resulting revision to Pinker’s game-theoretic framework that reflects this proposal. I conclude by demonstrating how this proposed game-theoretic framework of cooperation with multiple audiences can be used to model the costs and benefits of other types of discourse, including political speech

Virtues, Thrift Stores, and Consumption

Discourse in philosophy on fashion is relatively thin, this, in alignment with the typical disdain for clothing and dress from this field of study. However, there is some research that measures clothing brand addiction, attachment, digital culture, self-concept, and fashion communication. I aim to add to this research, particularly to the critique of fast fashion, to inform further philosophical conversations on the practice of dress, and not only argue that self-expression and sustainability can be best realized through second-hand shopping but that consumers have a moral obligation to do so, given the surplus material supply in existence. I will continue literature reviews of journal articles by philosophers, sociologists, and psychologists, and will also apply for funding to attend the American Society for Aesthetics conference where I will attend presentations on aesthetics, ethics, artistic, social, and environmental value, as well as conduct interviews with members who attend. I will also conduct interviews with various professors and students at USD on their dress and values. My findings will be mixed testimonies including claims of dressing for functionality, self-expression, and varying ideas of the value to dressing sustainably. With this data, I argue that clothing is intimately linked to personal identity, so dressing the body involves action and deliberation; I argue that this deliberation must attend to moral considerations. These include, how necessary one needs a new garment(s), who made the particular piece(s), what is the motivation for buying, and the likelihood of finding this piece(s) at a second-hand store

Tree Trimming: Four Non-Branching Rules for Priest’s Introduction to Non-Classical Logic

In An Introduction to Non-Classical Logic: From If to Is Graham Priest (2008) presents branching rules in Free Logic, Variable Domain Modal Logic, and Intuitionist Logic. I propose a simpler, non-branching rule to replace Priest’s rule for universal instantiation in Free Logic, a second, slightly modified version of this rule to replace Priest’s rule for universal instantiation in Variable Domain Modal Logic, and third and fourth rules, further modifying the second rule, to replace Priest’s branching universal and particular instantiation rules in Intuitionist Logic. In each of these logics the proposed rule leads to tableaux with fewer branches. In Intuitionist logic, the proposed rules allow for the resolution of a particular problem Priest grapples with throughout the chapter. In this paper, I demonstrate that the proposed rules can greatly simplify tableaux and argue that they should be used in place of the rules given by Priest

Meaning Through Things

Interpretation is the process by which we find meaning in the things in the world around us: clouds on the horizon, bones, street signs, hairbrushes, uniforms, paintings, letters, and utterances. But where does that meaning come from and on what basis are we justified in saying a particular meaning is the right meaning? Drawing from debates in the philosophy of language, I argue that a complete theory of meaning and interpretation must be grounded in intentions. My argument employs research in the philosophy of language, aesthetics, linguistics, and cognitive science to develop a general framework of interpretation. This framework is then broadly applied to objects of interpretation across a range of fields: legal theory, history, art history, theology, literature, and archaeology

Empowerment: An Idea Whose Time Has Come in Diabetes Education

We have learned much in the past 10 years about how to help patients to acquire diabetes-related knowledge and skills and how to use strategies to help patients change behaviors. However, the application ofknowledge and techniques should be guided by a relevant, coherent, educational philosophy. Empowerment offers a practical conceptual framework for diabetes patient education. Empowering patients provides them with the knowledge, skills, and responsibility to effect change and has the potential to promote overall health and maximize the use of available resources. It is an idea whose time has come for diabetes education.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68779/2/10.1177_014572179101700108.pd

Class-specific restrictions define primase interactions with DNA template and replicative helicase

Bacterial primase is stimulated by replicative helicase to produce RNA primers that are essential for DNA replication. To identify mechanisms regulating primase activity, we characterized primase initiation specificity and interactions with the replicative helicase for gram-positive Firmicutes (Staphylococcus, Bacillus and Geobacillus) and gram-negative Proteobacteria (Escherichia, Yersinia and Pseudomonas). Contributions of the primase zinc-binding domain, RNA polymerase domain and helicase-binding domain on de novo primer synthesis were determined using mutated, truncated, chimeric and wild-type primases. Key residues in the β4 strand of the primase zinc-binding domain defined class-associated trinucleotide recognition and substitution of these amino acids transferred specificity across classes. A change in template recognition provided functional evidence for interaction in trans between the zinc-binding domain and RNA polymerase domain of two separate primases. Helicase binding to the primase C-terminal helicase-binding domain modulated RNA primer length in a species-specific manner and productive interactions paralleled genetic relatedness. Results demonstrated that primase template specificity is conserved within a bacterial class, whereas the primase–helicase interaction has co-evolved within each species

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies

Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and potent effects in CD19+ B-cell malignancies. This scenario is ideal as CD19 expression is homogeneous and human blood provides a favorable environment for CAR-T cells to thrive and destroy cancer cells (along with normal B cells). Yet, CAR-T cell therapies for solid tumors remain challenged by fewer tumor targets and poor CAR-T cell performances in a hostile tumor microenvironment. For acute myeloid leukemia and childhood solid tumors such as osteosarcoma, the primary treatment is systemic chemotherapy that often falls short of expectation especially for relapsed and refractory conditions. We aim to develop a CAR-T adaptor molecule (CAM)-based therapy that uses a bispecific small-molecule ligand EC17, fluorescein isothiocyanate (FITC) conjugated with folic acid, to redirect FITC-specific CAR-T cells against folate receptor (FR)-positive tumors. As previously confirmed in rodents as well as in human clinical studies, EC17 penetrates solid tumors within minutes and is retained due to high affinity for the FR, whereas unbound EC17 rapidly clears from the blood and from receptor-negative tissues. When combined with a rationally designed CAR construct, EC17 CAM was shown to trigger CAR-modified T cell activation and cytolytic activity with a low FR threshold against tumor targets. However, maximal cytolytic potential correlated with (i) functional FR levels (in a semi-log fashion), (ii) the amount of effector cells present, and (iii) tumors' natural sensitivity to T cell mediated killing. In tumor-bearing mice, administration of EC17 CAM was the key to drive CAR-T cell activation, proliferation, and persistence against FR+ pediatric hematologic and solid tumors. In our modeling systems, cytokine release syndrome (CRS) was induced under specific conditions, but the risk of severe CRS could be easily mitigated or prevented by applying intermittent dosing and/or dose-titration strategies for the EC17 CAM. Our approach offers the flexibility of antigen control, prevents T cell exhaustion, and provides additional safety mechanisms including rapid reversal of severe CRS with intravenous sodium fluorescein. In this paper, we summarize the translational aspects of our technology in support of clinical development