Much progress has been made in recent years regarding the mechanisms of targeting of secretory proteins to, and across, the endoplasmic reticulum (ER) membrane. Many of the cellular components involved in mediating translocation across this bilayer have been identified and characterized. Polypeptide domains of secretory proteins, termed signal peptides, have been shown to be necessary, and in most cases sufficient, for entry of preproteins into the lumen of the ER. These NH2‐ terminal segments appear to serve multiple roles in targeting (...) and translocation. The structural features which mediate their multiple functions are currently the subject of intense study. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Triumph Of SisyphusJeffrey GordonThe gods had condemned Sisyphus to ceaselessly rolling a rock to the top of the mountain, whence the stone would fall back of its own weight. They had thought with some reason that there is no more dreadful punishment than futile and hopeless labor.1The words are, of course, Albert Camus's. They were first published in 1942. Since then, this voice—at once lyrical and austere, personal (...) and oracular—and the ancient image he calls up in these lines have become permanent parts of our postmodern consciousness. Like all the images that capture and create the character of our age, Sisyphus is always there for each of us. In the intimate space of our imagination, we can turn to him at will, and with only the slightest effort, we will find him as before—solitary, weather beaten, resigned, without illusion. I want to make that effort now, not to disturb Sisyphus in his labors, nor to uproot him, surely, but to try to be precise about a matter which is, perhaps, fatally elusive of precision, to try to make explicit the significance of this figure whose implicit significance has haunted us now for over half a century. Let us turn to Sisyphus, then, as we might turn, one aimless afternoon, to some old photographs of a person close to us, perhaps even of ourselves, in the hope that we might find in them something we had missed, some expression or gesture that inadvertently reveals the essence of a life.But we must be silent now, for the figure is emerging. There is the hill, and it is morning, a slight chill in the soundless air. The landscape here is treeless, the land covered only with broken rock and scattered brush. A wide path of sterile earth has been cut in the thick brush of [End Page 183] the hill. And there, at the base of the hill, the rock—grey, mottled with holes, enormous. Slow, laborious breathing is audible. The rough hand comes into view, the flesh thick, sun-burnt, heavily veined. It finds a jut on the rock to grip. And now the weather-worn clothes, the thick trunk and powerful back. And here at last the face of Sisyphus—our own face, of course, or the face of one of our own personae, the eyes squinting against the sun, hair disheveled. He takes his hand from the rock and brings it to his side. Perhaps he is not quite ready yet, perhaps he needs a moment longer of rest. He stands motionless, eyes turning up. What is he gazing at? The summit of the hill, every square inch of which he has seen a million times before? What could he hope to discover there? Is it the cloudless sky that has his attention? Is he noting the progress of the sun? Does he seek in reflection on its course some inspiration for the renewal of his labor? He continues to stare without expression. We can afford to leave him for a moment.The legend abounds in perplexities, or at least this is true of that retelling of the myth that has made it so important to us. Camus calls Sisyphus "the absurd hero." This is, then, the best that we can hope to be, for our lives, too, according to Camus, are absurd. But why should we believe this? Surely it is ludicrously question-begging to conduct an imaginative exercise in which we strip a life of all that could possibly make it worthwhile, then appeal to this figment of ours as proof of the futility of human existence.If we are tempted to see in Sisyphus's eternal rock-rolling a revelation of the emptiness of our own labors, we should be easily dissuaded from this when we consider what little alteration is required to transform this myth from the perfect image of meaninglessness to a perfectly serviceable conception of a meaningful life.2 All we need is to introduce some point, some minimal, common, everyday point to his labors, such as any one of our lives abounds in, and the transformation is accomplished. Assume, then, that Sisyphus rolls... (shrink)

‘The Will to Believe.’ The mere mention of this title cannot fail to elicit a reaction from philosophers. Written almost 100 years ago, it continues to intrigue, inspire, perplex and repel, often all in the selfsame reader. Few who make acquaintance with this robust and insightful lecture can remain neutral toward it. In 100 years there has been continuous debate about both the content of the argument and its merits. I will confess to being among those intrigued and inspired by (...) this lecture of James's – and, until recently, also much perplexed by it. The sources of my intrigue have been its guiding insights: that living is choosing in the midst of uncertainty; that in pressing cases, waiting for evidence is no escape from risk; and that believing can create certain truths. The sources of my inspiration have been its vibrant presence and its gallant call to courage. But the main source of my perplexity was the shape of the argument itself: Just what was James's case here? What was the conclusion? What were the premises? Off and on, I pondered the matter for years without resolution, and it was only after I abandoned the very frame of the question that I found a way out of my puzzlement. What I have come to see is that James is not pressing toward one key conclusion in ‘The Will to Believe’. There are two, the second far bolder, far more sweeping than the first. What makes this especially difficult to see is that James himself nowhere acknowledges it. Indeed, he expressly disavows the second conclusion, and this for good reason: The two conclusions are incompatible. In what follows, I want first to take you to the source of my problem in understanding James's classic lecture, then to explain to you why my two-argument theory seems its unavoidable if inelegant resolution. Finally, I want to turn to the properly philosophical task. I want to inquire into the truth of his more sweeping claim. (shrink)

In a century dominated by the exacting methods and dramatic successes of science, it is difficult to imagine an informed contemporary religious believer never shaken by the doubt that his or her most sacred ideas are atavisms to a benighted age, vain and empty fantasies. To such a believer, Freud's late monograph, The Future of an Illusion , with its warm, solicitous tone, but relentless scepticism, must seem the patient knell of his or her worst fears. For here Freud uses (...) his dialectical skill and his psychoanalysis to augment motives for self-doubt at least as old as Abraham: Perhaps the most cherished of my beliefs are a kind of madness, a condition I do not recognize because it is so widely shared. Perhaps like the madman bewitched by the tapestry of his delusions, I hold fast to my faith only because I could not endure the threadbare fabric of a life without it. But it is not as though the religionist is utterly without defence against this source of doubt, nor that the familiar defence is without considerable prima facie force against Freud. For when sceptics such as Freud turn their account of the origin of religious faith into a case against the truth of religious claims, the believer can attack this line with an unassailable axiom: No examination of the motives for a belief is relevant to an assessment of its truth. To assume otherwise is to commit the genetic fallacy. The question I want to deal with here is whether the religious believer should rest content with this rejoinder to Freud. (shrink)

Hume, Mill, And more recent thinkers have argued that the teleological conception of the universe must in the end revert to naturalism. I think these arguments are poor ones. As many have believed that a naturalistic universe is one in which man's life could have no meaning, I thought it important to spell out my grounds for this assessment.

In the first part of the paper, I try to clarify the cluster of moods and questions we refer to generically as the problem of the meaning of life. I propose that the question of meaning emerges when we perform a spontaneous transcendental reduction on the phenomenon my life, a reduction that leaves us confronting an unjustified and unjustifiable curiosity. In Part 2, I turn to the film ikiru, Kurosawa''s masterpiece of 1952, for an existentialist resolution of the problem.

No crucial experiment demonstrates that four hue categories are needed to describe color appearance. Instead, converging lines of evidence suggest that the terms red, yellow, green, and blue are sufficient and precise enough for deriving color discrimination functions and for a useful model constraining relations between color appearance and neuronal responses. Such a model need not be based on linguistic universals. Until something better is available, this holds.

Despite decades of research and thought on the meaning and identification of revolutions in science, there is no generally accepted definition for this concept. This paper presents 13 different characteristics that have been used by philosophers and historians of science to characterize revolutions in science, in general, and in chemistry, in particular. These 13 characteristics were clustered into six independent factors. Suggestions are provided as to the use of these characteristics and factors to evaluate historical events as to their possible (...) categorization as revolutions in chemistry. Challenges to the goal of creating a consensus definition of “revolutions in science” are also presented in this publication. (shrink)

Multiple simultaneous independent discoveries, so well enunciated by Robert K. Merton in the early 1960s but already discussed for several hundreds of years, is a classic concept in the sociology of science. In this paper, the concept of multiple simultaneous independent errors is proposed, analyzed, and discussed. The concept of Selective Pessimistic Induction is proposed and used to connect MIDs with MIEs. Five types of MIEs are discussed: multiple errors in the interpretation of experimental data or computational results; multiple misjudgments (...) of the value of another’s research results or conclusions; multiple cases of false anticipation of achieving a certain experimental result; multiples of ignoring or omitting relevant precedents; and multiple instances of failure due to a not-yet-conceived scientific concept or principle. Causal MIDs and MIEs are those that can be traced directly to antecedent knowledge. Acausal MIDs and MIEs are those involving a consequential and identifiable leap from antecedent knowledge. Examples of causal and acausal MIEs are provided, mostly but not exclusively from the discipline of chemistry. Comparisons are made between MIDs and MIEs. Topics for future research are discussed and implications of these concepts are proposed. (shrink)

Recent publications by several leading philosophers of chemistry have focused on the definition, scope, utility, and nomenclature of issues dealing with acidity and basicity. In this paper, molecular orbital theory is used to explain all acid–base reactions, concluding that the interaction of the highest occupied molecular orbital (HOMO) of one substrate, “the base,” with the lowest unoccupied molecular orbital (LUMO) of a second substrate, “the acid,” determines the reactivity of such systems. This paradigm provides an understanding of all acid–base reactions (...) as well as other reactions which, on the surface, may not seem like acid–base reactions but which have fundamental underpinnings of that kind of chemistry. Rather than being unable to determine a unified understanding of acidity and basicity as suggested in the philosophy of chemistry literature, we propose that acidity and basicity fit securely in a classification of many other reactions that, using classical chemistry knowledge, pre-quantum chemistry, would not be possible. We strongly support the use of all scientific knowledge and experience in the development of the ideas in the philosophy science. We further suggest increased interactions between philosophers of science and scientists, so that all scholars benefit from the values, knowledge, and perspectives of other disciplines. (shrink)

This essay supports and encourages multiple disciplinary interactions for practitioners of the disciplines of chemistry, history of chemistry, philosophy of chemistry, and sociology of chemistry.

Concussions in professional sports have received increased attention, which is partly attributable to evidence that found concussion incidence rates were much higher than previously thought. Further to this, professional hockey players articulated how their concussion symptoms affected their professional careers, interpersonal relationships, and qualities of life. Researchers are beginning to associate multiple/repeated concussions with Chronic Traumatic Encephalopathy, a structural brain injury that is characterized by tau protein deposits in distinct areas of the brain. Taken together, concussions impact many people in (...) the sporting community from current and former professional athletes and their families to medical and health professionals and researchers. In light of the growing awareness and sensitivity towards concussions, the purpose of this paper is to provide recommendations that are designed to improve player safety in professional hockey and address the ethical issues surrounding these suggestions. (shrink)

The process-dissociation procedure was used to estimate the influence of spatial and form-based processing in the Simon task. Subjects made manual responses to the direction of arrows . The results provide evidence that the form and spatial location of a single stimulus can have functionally independent effects on performance. They also indicate the existence of two kinds of automaticity—an associative component that reflects prior S-R mappings and a nonassociative component that reflects the correspondence between stimulus and response codes.

We consider an extension of signaling games to the case of prediction, where one agent perceives the current state of the world and sends a signal. The second agent perceives this signal, and makes a prediction about the next state of the world. We suggest that such games may be the basis of a model for the evolution of successful theorizing about the world.

Recent studies on the effects of mandatory online teaching, resulting from the COVID-19 pandemic, have widely reported low levels of satisfaction, unwillingness to continue online teaching, and negative impacts on the psychological well-being of teachers. Emerging research has highlighted the potential role of psychological need thwarting, in terms of autonomy, competence, and relatedness thwarting, resulting from online teaching. The aim of this study was to evaluate the immediate and delayed effects of PNT of online teaching on teachers’ well-being, intention to (...) continue online teaching, and job satisfaction. Moreover, data collected from both cross-sectional and longitudinal surveys allowed for a systematic validation of an important instrument in the field of teacher psychology, the Psychological Need Thwarting Scale of Online Teaching, in terms of longitudinal reliability and validity. The data reveal the usefulness of the construct of PNT in terms predicting and explaining teachers’ willingness to continue using online teaching as well as the degree of burnout after a period of 2 months, such that PNT is positively associated with burnout and negatively associated with willingness to continue online teaching. As such, the PNTSOT is recommended for future research evaluating the long-term psychological, affective, and intentional outcomes stemming from teachers’ PNT. Moreover, based on our findings that the impact from PNT of online teaching is persistent and long-term, we suggest that school leaders provide flexible and sustained professional development, model respectful and adaptive leadership, and create opportunities for mastery for the development of community of practice that can mitigate the thwarting of teachers’ autonomy, competence, and relatedness during times of uncertainty. Additionally, in terms of the psychometric properties of the PNTSOT instrument, our empirical findings demonstrate internal reliability, test–retest reliability, measurement invariance, and criterion validity based on cross-sectional and longitudinal data. (shrink)

Current arguments to increase shareholder power in the large public U.S. corporation need to take account of the well-established historical practice of extensive delegation by shareholders of business decision-making and agenda-control to management and the board, what might be characterized as an absolute delegation rule. This practice sharply limits the power of shareholders to put either business or governance proposals to the shareholders for dispositive resolution. The paper, originally published in 1991 but newly relevant, argues that the rule is based (...) on potential pathologies in shareholder voting rather than the inherent information asymmetry between shareholders and managers. Rational shareholders who know of this asymmetry (and know that others know) would simply vote against most shareholder proposals. But shareholder voting gives rise to potential cycling problems, as shifting shareholder majorities vie for preferred policies, and potential opportunism, as shareholders engage in side deals with management and other shareholders to extract rents in corporate decision-making. Since shareholding patterns are in part a response to control rights, deviations from the absolute delegation rule will predictably lead to greater block ownership, for defensive and offensive reasons. These concerns need to be addressed in arguments for the expansion of shareholder power. (shrink)

As medical technology becomes more sophisticate the ability to manipulate nature and manage disease forces the dilemma of when can becomes ought. Indeed, most bioethical discourse is framed in terms of balancing the values and interests and the benefits and burdens that inform principled decisions about how, when, and whether interventions should occur. Yet, despite advances in science and technology, one caregiver mandate remains as constant and compelling as it was for the earliest shaman—the relief of pain. Even when cure (...) is impossible, the physician's duty of care includes palliation. Moreover, the centrality of this obligation is both unquestioned and universal, transcending time and cultural boundaries.Although universally acknowledged, pain is a complex phenomenon for both the patient and the caregiver, influenced as much by personal values and cultural traditions as by physiological injury and disease. (shrink)