Molecular cloning of the genes encoding the muscarinic acetylcholine receptors has shwon that receptor subtypes classified on the basis of pharmacological properties are related polypeptides encoded by distinct genes. These studies have laso revealed the existence of novel muscarinic receptor subtypes. Functional analysis of each of the subtypes expressed in mammalian cells indicates that the different subtypes activate distinct biochemical pathways, a finding that explains the tissue‐specific physiological response elicited by the neurotransmitter, acetylcholine.

O taylorismo é identificado com o sistema de organização e administração do trabalho proposto, no início do século XX, por Frederick Winslow Taylor, e busca alcançar o máximo de produção e rendimento com o mínimo de tempo e de esforço despendidos, por meio de padronizações e simplificações num momento de expansão da indústria que exigiu grandes preocupações com a eficiência do trabalho. Apesar de vinculado inicialmente à atividade industrial, o taylorismo foi adaptado à racionalização das mais diversas atividades econômicas, (...) inclusive da agricultura. Neste texto será analisada a obra De re rustica de Columela como uma proposta de racionalização “taylorista” do trabalho em uma villa romana do século I a.C., marcada por processos de padronização e de organização do sistema produtivo rural. (shrink)

Locke and Leibniz deny that there are any such beings as ‘monsters’ (anomalies, natural curiosities, wonders, and marvels), for two very different reasons. For Locke, monsters are not ‘natural kinds’: the word ‘monster’ does not individuate any specific class of beings ‘out there’ in the natural world. Monsters depend on our subjective viewpoint. For Leibniz, there are no monsters because we are all parts of the Great Chain of Being. Everything that happens, happens for a reason, including a monstrous birth. (...) But what about materialism? Well, beginning with the anatomical interest into ‘monstrous births’ in the French Académie des Sciences in the first three decades of the eighteenth century, there is a shift away from ‘imaginationist’ claims such as those of Malebranche, that if a woman gives birth to a monstrous child it is a consequence of something she imagined. Anatomists such as Lemery and Winslow try to formulate a strictly mechanical explanation for such events, rejecting moral and metaphysical explanations. Picking up on this work, materialist thinkers like Diderot are compelled to reject the very idea of monsters. We are all material beings produced according to the same mechanisms or laws, some of us are more ‘successful’ products than others, i.e. some live longer than others. In his late Eléments de physiologie he says “L’homme est un effet commun, le monstre un effet rare.” Ultimately he arrives at a materialist version of Leibniz’s position: there are no monsters, we are all monsters in each other’s eyes, at one time or another. This conclusion is a pregnant one in light of twentieth century interest in the problem of ‘the normal and the pathological’ (Canguilhem), and the broader question of how materialism relates to the biological world. (shrink)

Folkbiology refers to people’s everyday understanding of the biological world. The early twentieth-century pioneers of public health C.-E.A Winslow (1877–1957), and his mentor H. Biggs (1859–1923), conceptualized public health as the ‘purchasable’ science of preventing disease and death from unfavorable economic and living conditions. Their ideas were foundational in shaping public health’s strategy of a ‘war against disease’ (Winslow, 1903), a strategy that was very successful in preventing the early-life mortality risks from infectious diseases, and was eventually extended (...) to combating the chronic diseases of late life (like cancer). However, the initial framing of public health, through the lens of sanitation science, was predicated upon folkbiological premises that geroscience must abate in order to direct public health interventions toward the goal of improving the quality of life for older persons in the twenty-first century. Three folkbiological premises of sanitation science’s ‘war against disease’ are identified and critiqued: (i) the belief that health is the ‘normal’ condition of the human mechanism and disease ‘unnecessary’; (ii) the belief that the proximate causes of disease are the only modifiable risk factors public health interventions can alter; and (iii) the belief that the rate of biological aging is universal. (shrink)

We present a population density and moment-based description of the stochastic dynamics of domain $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type $${\text{Ca}}^{2+}$$ channels. Our approach accounts for the effect of heterogeneity of local $${\text{Ca}}^{2+}$$ signals on whole cell $${\text{Ca}}^{2+}$$ currents; however, in contrast with prior work, e.g., Sherman et al. :985–995, 1990), we do not assume that $${\text{Ca}}^{2+}$$ domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model (...) of an L-type $${\text{Ca}}^{2+}$$ channel introduced by Greenstein and Winslow :2918–2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell $${\text{Ca}}^{2+}$$ current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of $${\text{Ca}}^{2+}$$ inactivation that may occur via slow heterogeneous domain [ $${\text{Ca}}^{2+}$$ ]. Next, we find that when channel permeability is held constant, $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type channels increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [ $${\text{Ca}}^{2+}$$ ] near open channels; conversely, when the maximum domain [ $${\text{Ca}}^{2+}$$ ] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations. (shrink)

Background: Breaches of publication ethics such as plagiarism, data fabrication and redundant publication are recognised as forms of research misconduct that can undermine the scientific literature. We surveyed journal editors to determine their views about a range of publication ethics issues. Methods: Questionnaire sent to 524 editors-in-chief of Wiley-Blackwell science journals asking about the severity and frequency of 16 ethical issues at their journals, their confidence in handling such issues, and their awareness and use of guidelines. Results: Responses were obtained (...) from 231 editors (44%), of whom 48% edited healthcare journals. The general level of concern about the 16 issues was low, with mean severity scores of <1 (on a scale of 0–3) for all but one. The issue of greatest concern (mean score 1.19) was redundant publication. Most editors felt confident in handling the issues, with <15% feeling “not at all confident” for all but one of the issues (gift authorship, 22% not confident). Most editors believed such problems occurred less than once a year and >20% of the editors stated that 12 of the 16 items never occurred at their journal. However, 13%–47% did not know the frequency of the problems. Awareness and use of guidelines was generally low. Most editors were unaware of all except other journals’ instructions. Conclusions: Most editors of science journals seem not very concerned about publication ethics and believe that misconduct occurs only rarely in their journals. Many editors are unfamiliar with available guidelines but would welcome more guidance or training. (shrink)

Studies examining the ways in which the training of engineers and scientists shapes their research strategies and scientific identities.

Institutional investors are increasingly becoming active owners through voting their shares and engaging in dialogue with investee companies to improve corporate environmental, social and corporate governance (ESG) performance. This article applies a model of stakeholder salience to the shareholder context, analysing the attributes of power, legitimacy and urgency, to determine the factors that are likely to enhance shareholder salience. It is found that a strong business case and the values of the managers of investee companies are likely to be the (...) most important contributors to shareholder salience. (shrink)

Business firms have been explained as internal markets or as communities. To be sustainable, however, they need to reconcile these two constituting elements that have mainly been touted as opposite and part of a dualistic relationship. We suggest that organizations may, in alternative, view market and community as part of a duality, interdependent and mutually constituting processes that may not only contradict each other but also enable one another. The implications of a duality view for business ethics, which articulates market (...) and community elements in a fruitful, mutually enabling relationship, are considered, and duality is presented as a way of transcending what is commonly viewed as opposition, moving organizations both in the direction of humane and competitive finalities. (shrink)

The behavior of individuals currently living will generally have long-term consequences that affect the well-being of those who will come to live in the future. Intergenerational interdependencies of this nature raise difficult moral issues because only the current generation is in a position to decide on actions that will determine the nature of the world in which future generations will live. Although most are willing to attach some weight to the interests of future generations, many would argue that it is (...) not necessary to treat these interests as equivalent to those of the current generation. A common approach in this context is to use a system of discounting to evaluate future benefits and harms. This paper assesses the logic of discounting drawing on the writings of economists and philosophers. Much of the economic literature concerns the choice of an appropriate social discount rate. The social discount rate can be taken to reflect beliefs about the rights of future generations, a subject that has been extensively debated in the phioosophic literature. The writings of both economists and philosophers concerned with the weight to attach to the interests of future generations are reviewed and evaluated in this paper and the implications for environmental policy are discussed. (shrink)

Este ensaio pretende levantar as seguintes questões: 1. de que modo é possível reconstituir o sentido de moral segundo um amor-próprio cujo conteúdo é dado menos por um isolamento ou negaçáo do outro do que por um trabalho pessoal sobre si mesmo, em vista de um êthos , de uma ética? 2. em que medida o valor da moral hoje em dia pode ser deslocado da lei universal para uma atitude de diferença, da normalidade do comportamento para o cultivo de (...) si e, por fim, da verdade sobre o sujeito para uma subjetivaçáo ascética que náo exige a prerrogativa de uma identidade, mas a transformaçáo de si na relaçáo consigo e com os outros? Tais questões sáo levantadas a partir de Friedrich Nietzsche, Michel Foucault e Fernando Savater. Palavras-chave: Amor-próprio, Estética da existência, Ética, Identidade. (shrink)

E. J. Lowe; Indicative and counterfactual conditionals, Analysis, Volume 39, Issue 3, 1 June 1979, Pages 139–141, https://doi.org/10.1093/analys/39.3.139.

Let’s say that you are omniprescient iff you always believe—occurrently and with maximal confidence—all and only truths, including ones about the future. Several philosophers have argued that an omniprescient being couldn’t engage in certain kinds of activity.[1] In what follows, I present and assess the most promising such argument I know of—what I’ll call the Serious Deliberation Argument (SDA). It concludes that omniprescience rules out serious deliberation—i.e., trying to choose between incompatible courses of action once you know that none is (...) conclusively favored by your reasons.[2] The SDA—which (I’ll argue) should disturb many traditional theists—derives from an argument due to Tomis Kapitan[3]; and my favored objection to the SDA—roughly: that it fails because dependent on the alleged incompatibility of omniprescience and freedom—superficially resembles a reply to Kapitan’s argument due to David Hunt.[4] Along the way, then, I’ll briefly discuss Kapitan’s argument, and Hunt’s reply, to show how they differ from the SDA and my favored objection to it. I begin by presenting the Serious Deliberation Argument. (shrink)

This paper assesses several prominent recent attacks on the view that epistemic justification is conceptually prior to knowledge. I argue that this view—call it the Received View (RV)—emerges from these attacks unscathed. I start with Timothy Williamson’s two strongest arguments for the claim that all evidence is knowledge (E>K), which impugns RV when combined with the claim that justification depends on evidence. One of Williamson’s arguments assumes a false epistemic closure principle; the other misses some alternative (to E>K) explanations of (...) a putative fact about the evidence a particular subject has. Next, I neutralize each of Jonathan Sutton’s three recent arguments to the conclusion that any justified belief constitutes knowledge. Finally, I consider a recent analysis of justification due to Alexander Bird, according to which justified belief is possible knowledge. I argue that Bird’s analysis delivers neither a sufficient nor (more importantly) a necessary condition for justification. [Word count: 149]. (shrink)

The jaw mechanism of cichlid fishes is an intricate apparatus with complex force transmission from muscles to environment. The proportions of this apparatus change considerably during growth mainly due to scale effects. In adult fishes, the proportions differ, corresponding with the type of preferred food. In such a complex mechanism, it is very hard to gain insight into the functional meaning of the differences in proportions, unless a biomechanical model is constructed, describing kinematics and force equilibria of the apparatus.Such a (...) model has been constructed and by means of perturbation analysis anatomical points could be selected of which the positions are very important for the function of biting. These hot spots need only small displacements in order to obtain an increase in biting force. By means of a newly developed mathematical technique, it was possible to move the anatomical points in very small steps towards more favourable positions for the function of biting. (shrink)

Cet ouvrage se propose de mener l'enquête tant sur les accusations de scepticisme et sur les modes de défenses spécifiques que ces dernières imposent de mettre en place, que sur la façon dont les mêmes arguments circulent et peuvent servir à des projets contraires. Cette perspective polémique permet ainsi de s'interroger sur les étiquettes philosophiques, sur la circulation des arguments, et sur leur force et leur portée, non seulement au sein du corpus sceptique, mais aussi à l'intérieur des systèmes sommés (...) de répondre aux questions qu'ils posent."--Page 4 of cover. (shrink)