To understand how the photoreceptor protein rhodopsin performs in its role as a receptor, its structure needs to be determined at the atomic level. Upon receiving a photon of light, rhodopsin undergoes a change in conformation that allows it to bind and activate the C-protein, transducin. An important future goal should be to determine the structure of both the inactive and the photoactivated state of rhodopsin, R*. This should provide the groundwork necessary for experiments on how rhodopsin achieves its signaling (...) state R*, and how R* functions to activate transducin. To do this, the crystal structure of both rhodopsin and R* must be determined. Few membrane proteins have been successfully crystallized, so this is not a trivial undertaking. Two- or three dimensional crystals of rhodopsin must be prepared that are well ordered, to produce a high-resolution structure. Rhodopsin must be purified to homogeneity and the appropriate detergent(s) selected for crystallization experiments. Long-term thermal stability of the rhodopsin-detergent complex must be achieved in the presence of a precipitant. Two-dimensional crystals may offer advantages in investigating the structure of R*, but the structure obtained may be limited in resolution. It is necessary to work with rhodopsin in the dark, unless suitable light-stable retinal derivatives are developed. Protein engineering of rhodopsin offers attractive opportunities to improve its ability to crystallize, but is presently hindered by the absence of a high-yielding expression system. Knowledge of the structure of rhodopsin will have general importance. Because rhodopsin is a member of the family of C-protein-coupled receptors, knowledge of the structure and the mechanism of action of rhodopsin suggests by analogy how other members of the receptor family may function. (shrink)

Philosophers and scientists are concerned with the why and the how of things. Questions like the following are so much grist for the philosopher’s and scientist’s mill: How can we be free and yet live in a deterministic universe?, How do neural processes give rise to conscious experience?, Why does conscious experience accompany certain physiological events at all?, How is a three-dimensional perception of depth generated by a pair of two-dimensional retinal images?. Since Belnap and Steel’s pioneering work on (...) the logic of questions, Van Fraassen has managed to apply their approach in constructing an account of the logic of why-questions. Comparatively little, by contrast, has been written on the logic of how-questions despite the apparent centrality of questions such as How is it possible for us to be both free and determined? to philosophical enterprise.1 In what follows I develop a logic for how-questions of various sorts including how-questions of cognitive resolution, how-questions of manner, how-questions of method, of means, and of mechanism. (shrink)

Magic angle spinning (MAS) NMR methods provide a means of obtaining high resolution structural data on rhodopsin and its photoin termediates. Current work has focused on the structure of the retinal chromophore and its interactions with surrounding protein charges. The recent development of MAS NMR methods for measuring internuclear distances with a resolution of ∼0.2 will complement diffraction methods for addressing key mechanistic questions.

According to an influential philosophical view I call “the relational properties view”, “perspectival” properties, such as the elliptical appearance of a tilted coin, are relational properties of external objects. Philosophers have assessed this view on the basis of phenomenological, epistemological or other purely philosophical considerations. My aim in this paper is to examine whether it is possible to evaluate RPV empirically. In the first, negative part of the paper I consider and reject a certain tempting way of doing so. In (...) the second, positive part of the paper I suggest a novel way of evaluating RPV empirically, relying on the influential object files framework. (shrink)

A judge springs out of his car on the way to court in downtown Chicago and takes photographs of an inflatable rat. A while later he inserts these photographs into a decision involving another inflatable rodent. Judges now regularly insert pictures in judgments, but there is no study either of the genres or the precedential status of these modern visual emblemata, these pictorial interventions in the record. Using a comparative visual corpus of over three hundred images extracted from diverse common (...) law jurisdictions, the practice of retinal justice, the novelty of vision in decision, is here anatomized, choreographed, and critically classified. (shrink)

How does neuronal activity give rise to cognitive capacities? To address this question, neuroscientists hypothesize about what neurons “represent,” “encode,” or “compute,” and test these hypotheses empirically. This process is similar to the assessment of hypotheses in other fields of science and as such is subject to the same limitations and difficulties that have been discussed at length by philosophers of science. In this paper, we highlight an additional difficulty in the process of empirical assessment of hypotheses that is unique (...) to the cognitive sciences. We argue that, unlike in other scientific fields, comparing hypotheses according to the extent to which they explain or predict empirical data can lead to absurd results. Other considerations, which are perhaps more subjective, must be taken into account. We focus on one such consideration, which is the purposeful function of the neurons as part of a biological system. We believe that progress in neuroscience critically depends on properly addressing this difficulty. (shrink)

In Willing, Wanting, Waiting, Richard Holton lays out a detailed account of resolutions, arguing that they enable agents to resist temptation. Holton claims that temptation often leads to inappropriate shifts in judgment, and that resolutions are a special kind of first- and second-order intention pair that blocks such judgment shift. In this paper, I elaborate upon an intuitive but underdeveloped objection to Holton’s view – namely, that his view does not enable agents to successfully block the transmission of temptation in (...) the way that he claims, because the second-order intention is as equally susceptible to temptation as the first-order intention alone would be. I appeal to independently compelling principles – principles that Holton should accept, because they help fill an important explanatory gap in his account – to demonstrate why this objection succeeds. This argument both shows us where Holton’s view goes wrong and points us to the kind of solu-tion we need. In conclusion, I sketch an alternative account of resolutions as a first-order intention paired with a second-order desire. I argue that my account is not susceptible to the same objection because a temptation that cannot be blocked by an intention can be blocked by a desire. (shrink)

Abstract: “Resolute readings” initially started life as a radical new approach to Wittgenstein's early philosophy, but are now starting to take root as a way of interpreting the later writings as well—a trend exemplified by Stephen Mulhall's Wittgenstein's Private Language (2007) as well as by Phil Hutchinson's “What's the Point of Elucidation?” (2007) and Rom Harré's “Grammatical Therapy and the Third Wittgenstein” (2008). The present article shows that there are neither good philosophical nor compelling exegetical grounds for accepting a resolute (...) reading of the later Wittgenstein's work. It is possible to make sense of Wittgenstein's philosophical method without either ascribing to him an incoherent conception of “substantial nonsense” or espousing the resolute readers' preferred option of nonsense austerity. If the interpretation here is correct, it allows us to recognize Wittgenstein's radical break with the philosophical tradition without having to characterize his achievements in purely therapeutic fashion. (shrink)

Discussion of temptation has figured prominently in recent debates concerning instrumental rationality. In light of some particularly interesting cases in which giving in to temptation involves acting in accordance with one’s current evaluative rankings, two lines of thought have been developed: one appeals to the possibility of deviating from a well-grounded resolution, and the other appeals to the possibility of being insufficiently responsive to the prospect of future regret. But the current appeals to resolutions and regret and some of (...) the verdicts provided face some serious challenges. Building on recent work concerning instrumental rationality, and delving into some important complications concerning human psychology, I revisit the relevant cases of temptation and analyze them in a way that puts resolutions, rational failure, and regret in their proper places. In the process, I highlight and explain the significance of the neglected fact that resolutions can introduce effective anchor points, which can serve agents faced with temptation well, even if the resolutions are abandoned. (shrink)

Metamorphosis in frogs is a critical developmental process through which a tadpole changes into an adult froglet. Metamorphic changes include external morphological transformations as well as important changes in the wiring of sensory organs and central nervous system. This review aims to provide an overview on the events that occur in the visual system of metamorphosing amphibians and to discuss recent studies that provide new insight into the molecular mechanisms that control changes in the retinal growth pattern as well (...) as the formation of new axonal pathways in the central nervous system. BioEssays 23:319–326, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

‘Conciliationism’ is the view that disagreement with qualified disputants gives us a powerful reason for doubting our disputed views, a reason that will often be sufficient to defeat what would otherwise be strong evidential justification for our position. Conciliationism is disputed by many qualified philosophers, a fact that has led many to conclude that conciliationism is self-defeating. After examining one prominent response to this challenge and finding it wanting, I develop a fresh approach to the problem. I identify two levels (...) at which one may show epistemic deference—the level of one's credences and the level of one's reasoning—and show that in disagreements over conciliationism, deference at one level results in non-deference at the other. A commitment to epistemic deference therefore does not provide a rational reason to reduce confidence when conciliationism itself is disputed. After presenting the case for ‘resolute conciliationism’, I address two objections. (shrink)

The foundational hypothesis to this study is that congregations which have a healthy perception and a greater understanding of conflict will develop more effective responses to conflict that will translate into more effective conflict resolution and reconciliation. The process and sustainability of the development of a missional church, the context of the study, is pregnant with potential conflict. Untamed conflict has the propensity to retard, jeopardise or even destroy the development of a missional church. When conflict arises, it must (...) be understood and dealt with theologically. The inherent problem is that conflict appears to be neither understood nor appreciated sociologically and theologically. This knowledge and praxis vacuum has the potential for conflict to translate into inappropriate or ineffective responses that do not always make for effective resolution and reconciliation. The research focuses mainly on an empirical study based on the four practical theological questions of Osmer (2008). Participants for this study were randomly selected from specific sectors of Methodist congregations in the wider Pretoria area. The research explores congregants’ perceptions, understanding and views of conflict; their responses to conflict; and some felt and observed outcomes of conflict. The presupposition is that the development of the local missional church would be more effective and efficient when the management and process of conflict resolution and reconciliation are well led and well managed. This study confirmed that conflict, despite its normalcy and necessity, carries a negative undertone and is mostly avoided in congregations. This is compounded by the evidence that there is little, if any, theological or scriptural understanding of conflict. There is also no indication that churches intentionally and purposefully educate their members to appreciate and understand conflict. In so doing, churches are harming their innate calling as the glory and manifestation of God’s divine grace through faith communities for the transformation of all peoples. Yet, the church understands the dangers of unhealthy conflict, and on occasion even expects conflict to arise, although deeming it inappropriate. Practical theological discernment is sought as to why this may be so and remedial action is proposed to address the problem of conflict within congregations. (shrink)

A pool resolution proof is a dag-like resolution proof which admits a depth-first traversal tree in which no variable is used as a resolution variable twice on any branch. The problem of determining whether a given dag-like resolution proof is a valid pool resolution proof is shown to be NP-complete.

A spectator of the passing philosophical scene, recently encountering the current controversy about “resolute readings” of the Tractatus, might be forgiven for finding it difficult to figure out what the debate is supposed to be about and who exactly is on which side and why. This chapter demonstrates, through a reconstruction of some relevant features of “the” debate, that at one point there are in fact several orthogonal debates taking place, confusedly cast as contributions to a single debate. It indicates (...) some of the respects in which the term “resolute reading” has come to acquire different meanings, and sometimes even a different logic. The chapter traces the shifts in the meaning of the term “resolute reading” and the related family of cognate and contrastive expressions. Cora Diamond and James Conant are often presented as the main proponents of a “resolute reading” of the Tractatus. (shrink)

Sensorimotor theorists of perception have argued that eye movement is a necessary condition for seeing on the basis that subjects whose retinal images do not move undergo a form of blindness. I show that the argument does not work.

The use of super‐resolution imaging techniques in cell biology has yielded a wealth of information regarding cellular elements and processes that were invisible to conventional imaging. Focusing on images obtained by stimulated emission depletion (STED) microscopy, we discuss how the new high‐resolution data influence the ways in which we use and interpret images in cell biology. Super‐resolution images have lent support to some of our current hypotheses. But, more significantly, they have revealed unexpectedly complex processes that cannot (...) be accounted for by the simpler models based on diffraction‐limited imaging. The super‐resolution imaging data challenge cell biologists to change their theoretical framework, by including, for instance, interpretations that describe multiple functions, functional errors or lack of function for cellular elements. In this context, we argue that descriptive research using super‐resolution microscopy is now as necessary as hypothesis‐driven research. (shrink)

In the 1920s, Paul Hertz (1881-1940) developed certain calculi based on structural rules only and established normal form results for proofs. It is shown that he anticipated important techniques and results of general proof theory as well as of resolution theory, if the latter is regarded as a part of structural proof theory. Furthermore, it is shown that Gentzen, in his first paper of 1933, which heavily draws on Hertz, proves a normal form result which corresponds to the completeness (...) of prepositional SLD-resolution in logic programming. (shrink)

Bertrand's random-chord paradox purports to illustrate the inconsistency of the principle of indifference when applied to problems in which the number of possible cases is infinite. This paper shows that Bertrand's original problem is vaguely posed, but demonstrates that clearly stated variations lead to different, but theoretically and empirically self-consistent solutions. The resolution of the paradox lies in appreciating how different geometric entities, represented by uniformly distributed random variables, give rise to respectively different nonuniform distributions of random chords, and (...) hence to different probabilities. The principle of indifference appears consistently applicable to infinite sets provided that problems can be formulated unambiguously. (shrink)

This paper presents a formulation and completeness proof of the resolution-type calculi for the first order fragment of Girard's linear logic by a general method which provides the general scheme of transforming a cutfree Gentzen-type system into a resolution type system, preserving the structure of derivations. This is a direct extension of the method introduced by Maslov for classical predicate logic. Ideas of the author and Zamov are used to avoid skolomization. Completeness of strategies is first established for (...) the Gentzen-type system, and then transferred to resolution. The propositional resolution system was implemented by T. Tammet. (shrink)

Why should we typically act in accordance with our resolutions when faced with the temptation to do otherwise? A much-maligned view suggests that we should do so because resolutions themselves provide us with reasons for action. We defend a version of this view, on which resolutions provide second-order reasons. This account avoids the objections typically taken to be fatal for the view that resolutions are reasons, including the prominent bootstrapping objections.

It may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. Because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. The eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. Currently, adenovirus, adeno‐associated virus and lentivirus have been used (...) to successfully transfer genetic material to retinal pigment epithelium and photoreceptor cells. By harnessing therapeutic genes to these viruses, researchers have been able to demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence that this form of therapy can be effective in delaying photoreceptor cell death. Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long‐term rescue with minimal toxicity. BioEssays 23:662–668, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Resolution of quarrels arising from conflicting sacred values, as in the Middle East, may require concessions that acknowledge the opposition's core concerns.

It is well known that when resolution occurs in the stichic iambics and trochaics of tragedy word-end is not found between the two shorts so produced: w or, more accurately, that the first short of resolution must not be the last syllable of a polysyllabic word. Moreover, the syllables in resolution most often form part of the same word as the following short or anceps, e.g.: Ion 1143.