A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

Convex Cycle Bases

Convex cycles play a role e.g. in the context of product graphs. We introduce convex cycle bases and describe a polynomial-time algorithm that recognizes whether a given graph has a convex cycle basis and provides an explicit construction in the positive case. Relations between convex cycles bases and other types of cycles bases are discussed. In particular we show that if G has a unique minimal cycle bases, this basis is convex. Furthermore, we characterize a class of graphs with convex cycles bases that includes partial cubes and hence median graphs. (authors' abstract)Series: Research Report Series / Department of Statistics and Mathematic

Immersive Interactive Quantum Mechanics for Teaching and Learning Chemistry

The impossibility of experiencing the molecular world with our senses hampers teaching and understanding chemistry because very abstract concepts (such as atoms, chemical bonds, molecular structure, reactivity) are required for this process. Virtual reality, especially when based on explicit physical modeling (potentially in real time), offers a solution to this dilemma. Chemistry teaching can make use of advanced technologies such as virtual-reality frameworks and haptic devices. We show how an immersive learning setting could be applied to help students understand the core concepts of typical chemical reactions by offering a much more intuitive approach than traditional learning settings. Our setting relies on an interactive exploration and manipulation of a chemical system; this system is simulated in real-time with quantum chemical methods, and therefore, behaves in a physically meaningful way.Comment: 16 pages, 4 figure

14th Annual Reception Bibliography, 1996-1997

Since 1984, Leonard H. Axe Library at Pittsburg State University has honored book authors and other creators for their outstanding scholarship and contributions to their fields

Back to the events themselves: on what events are and how we perceive them

A task confronting all the theoretical branches of philosophy is Peacocke’s Integration Challenge: “providing, for a given area, a simultaneously acceptable metaphysics and epistemology, and showing them to be so” (1999, 1). When it comes to the study of everyday events such as basketball shots and ripples on a pond, there is a phenomenological analogue of the Integration Challenge: the twofold task of explicating both the nature of such events and the way they show up in our perceptual consciousness. In this dissertation, I propose an account of events in response to the twofold challenge. On the one hand, an event is a complex entity constituted from tropes in accordance with its kind. On the other hand, our perceptual experiences of events differ from our other varieties of experiences because they uniquely feature the awareness of certain temporal phenomena that function as the boundaries between events. The dissertation is divided into five chapters. After a short introductory chapter, I develop a metaphysical theory of events. I follow a framework based on Evnine (2016) and divide theories of events into two groups: those that invoke the constitution relation and those that do not. Chapter 2 reviews and argues against the major theories in the first group, whereas Chapter 3 defends my own view against several alternatives in the second group. Roughly, my view is that a number of events jointly constitute another if and only if the event-kind the latter falls under makes the latter dependent upon the former. The remaining chapters defend a Husserlian view about event perception. Chapter 4 situates my favored view in the theoretical landscape. I argue for a representational view by drawing on Husserlian ideas, in particular the idea that any perceptual content has an expectational component in addition to a component that represents what is strictly visible. Chapter 5 expands on the view and supplies an analysis of event perception. By combining the theory of perceptually based expectations proposed by Yoshimi (2016) with results from linguistics and psychology, I argue that event perception can be better understood with the theoretical apparatus of possible worlds

Testing the Substrate-Envelope Hypothesis with Designed Pairs of Compounds

Acquired resistance to therapeutic agents is a significant barrier to the development of clinically effective treatments for diseases in which evolution occurs on clinical time scales, frequently arising from target mutations. We previously reported a general strategy to design effective inhibitors for rapidly mutating enzyme targets, which we demonstrated for HIV-1 protease inhibition [Altman et al. J. Am. Chem. Soc. 2008, 130, 6099–6113]. Specifically, we developed a computational inverse design procedure with the added constraint that designed inhibitors bind entirely inside the substrate envelope, a consensus volume occupied by natural substrates. The rationale for the substrate-envelope constraint is that it prevents designed inhibitors from making interactions beyond those required by substrates and thus limits the availability of mutations tolerated by substrates but not by designed inhibitors. The strategy resulted in subnanomolar inhibitors that bind robustly across a clinically derived panel of drug-resistant variants. To further test the substrate-envelope hypothesis, here we have designed, synthesized, and assayed derivatives of our original compounds that are larger and extend outside the substrate envelope. Our designs resulted in pairs of compounds that are very similar to one another, but one respects and one violates the substrate envelope. The envelope-respecting inhibitor demonstrates robust binding across a panel of drug-resistant protease variants, whereas the envelope-violating one binds tightly to wild type but loses affinity to at least one variant. This study provides strong support for the substrate-envelope hypothesis as a design strategy for inhibitors that reduce susceptibility to resistance mutations.National Science Foundation (U.S.) (NSF grant 0821391)National Institute of General Medical Sciences (U.S.) (NIH (GM066524))National Institute of General Medical Sciences (U.S.) (GM065418)National Institute of General Medical Sciences (U.S.) (the NIH (GM082209)National Institute of General Medical Sciences (U.S.) (AI41404)National Institute of General Medical Sciences (U.S.) (AI43198

A solution to skeptical puzzles

"May 2014."Dissertation Supervisor: Dr. Matthew McGrath.Includes vita.In this dissertation, I aim at resolving the skeptical puzzle. An instance of this puzzle is as follows: (1) I know that I have hands. (2) I don't know that I am not a brain in a vat (being stimulated to experience having hands). (3) If I know that I have hands, I know that I am not a brain in a vat. (1)-(3) are puzzling since, while each is individually plausible, they are jointly inconsistent. Siding with epistemic contextualism, I argue that the truth values of (1)-(3) vary with contexts. More precisely, (1), not-(2) and (3) are true in the ordinary context, while not-(1), (2), and (3) are true in the skeptical context. However, contextualists claim that the variability of the truth values consists in the variability of the standards for knowledge, while I claim that the variability is due to the variability of one's epistemic position with respect to p. I argue against the contextualist solution. I propose that one's epistemic position with respect to p should be characterized by the sensitivity of one's reason, where S's reason for p is sensitive just in case S would not have the same reason if p had not been the case. I argue that the assessment of the sensitivity of one's reason for p is relative to the epistemic inquiry the assessor is engaging in. There are two basic kinds of epistemic inquiry, defining by two distinct epistemic goals: the liberal goal and the conservative goal. I argue that (1) and not-(2) are true relative to the liberal inquiry, while not-(1) and (2) are true relative to the conservative inquiry. This explains why (1) and not-(2) are true in the ordinary context, while not-(1) and (2), the skeptical one.Includes bibliographical references (pages 287-294)