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)

Responding to volatile criticisms frequently leveled at Leo Strauss and those he influenced, the prominent contributors to this volume demonstrate the profound influence that Strauss and his students have exerted on American liberal democracy and contemporary political thought. By stressing the enduring vitality of classic books and by articulating the theoretical and practical flaws of relativism and historicism, the contributors argue that Strauss and the Straussians have identified fundamental crises of modernity and liberal democracy.

Plato's Euthyrphro, Apology, andCrito portray Socrates' words and deeds during his trial for disbelieving in the Gods of Athens and corrupting the Athenian youth, and constitute a defense of the man Socrates and of his way of life, the philosophic life. The twelve essays in the volume, written by leading classical philosophers, investigate various aspects of these works of Plato, including the significance of Plato's characters, Socrates's revolutionary religious ideas, and the relationship between historical events and Plato's texts.

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

This volume brings together mostly previously unpublished studies by prominent historians, classicists, and philosophers on the roles and effects of religion in Socratic philosophy and on the trial of Socrates. Among the contributors are Thomas C. Brickhouse, Asli Gocer, Richard Kraut, Mark L. McPherran, Robert C. T. Parker, C. D. C. Reeve, Nicholas D. Smith, Gregory Vlastos, Stephen A. White, and Paul B. Woodruff.

Extending the dialogue on corporate social performance (CSP) as descriptive stakeholder management (Clarkson, Acad Manage Rev 20: 92, 1995), we examine differences in CSP activity between family and nonfamily firms. We argue that CSP activity can be explained by the firm's identity orientation toward stakeholders (Brickson, Admin Sci Quart 50: 576, 2005; Acad Manage Rev 32: 864, 2007). Specifically, individualistic, relational, or collectivistic identity orientations can describe a firm's level of CSP activity toward certain stakeholders. Family firms, we suggest, adopt (...) a more relational orientation toward their stakeholders than nonfamily firms, and thus engage in higher levels of CSP.Further, we invoke collectivistic identity orientation to argue that the higher the level of family or founder involvement within a family firm, the greater the level of CSP toward specific stakeholders. Using social performance rating data from 1991 to 2005, we find that family and nonfamily firms demonstrate notable differences in terms of social initiatives and social concerns. We also find that the level of family and founder involvement is related to the type and frequency of a family firm's social initiatives and social concerns. (shrink)

The sciences are characterized by what is sometimes called a “methodological naturalism,” which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have (...) always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself. (shrink)

We posit a key goal of firms’ corporate social responsibility efforts is to influence reputation through carefully crafted communicative practices. This trend has accelerated with the rise of social media such as Twitter and Facebook, which are essentially public message networks that organizations are leveraging to engage with concerned audiences. Given the large number of messages sent on these sites, only some will be effective and achieve broad public resonance. Building on signaling theory, this paper asks whether and how messages (...) conveying CSR-related topics resonate with the public and, if so, which CSR topics and signal qualities are most effective. We test our hypotheses using data on public reactions to Fortune 500 companies’ CSR-focused Twitter feeds, using the retweeting of firms’ messages as a proxy for public resonance. We find resonance is positively associated with messages that convey CSR topics such as the environment or education, those that make the topic explicit through use of hashtags, and those that tap into existing social movement discussions. (shrink)

Social media offers a platform for diffused stakeholders to interact with firms—alternatively praising, questioning, and chastising businesses for their CSR performance and seeking to engage in two-way dialogue. In 2014, 163,402 public messages were sent to Fortune 200 firms’ CSR-focused Twitter accounts, each of which was either shared, replied to, “liked,” or ignored by the targeted firm. This paper examines firm reactions to these messages, building a model of firm response to stakeholders that combines the notions of CSR communication and (...) stakeholder salience. Our findings show that firm response to a stakeholder on social media is positively and most significantly associated with what we refer to as the stakeholder’s connective power but negatively associated with the firm’s own connective power. To a lesser extent, firm response is positively associated with the stakeholder’s normative power but negatively associated with the firm’s own normative power. Firm response is also shown to be positively associated with stakeholder urgency in terms of both the originality of a stakeholder message and the expression of positive sentiment. (shrink)

Social media is changing social accountability practices. The release of the Panama Papers on April 3, 2016 by the International Consortium of Investigative Journalists (ICIJ) unleashed a tsunami of over 5 million tweets decrying corrupt politicians and tax-avoiding business elites, calling for policy change from governments, and demanding accountability from corporate and private tax avoiders. The current study uses 297,000+ original English-language geo-codable tweets with the hashtags #PanamaGate, #PanamaPapers, or #PanamaLeaks to examine the trajectory of Twitter-based social accountability conversations and (...) the potential for the emergence of a longer-term social accountability user network. We propose that it is the combination of financial inscriptions and evaluative ethical utterances that incite and sustain social accountability conversations and social accountability networks. Financial inscriptions simultaneously remind audiences of both the information event that fomented the initial public reaction and the monetary magnitude of the event. Value-based ethical messaging, in turn, enunciates an ethical stance that simultaneously evaluates existing practices and emphasizes the need for accountability. It is the combining of these two types of messaging that helps to construct and sustain a normative narrative about social accountability. The results illustrate how the repetition and re-working of these two forms of messaging facilitated the construction of a normative narrative that coalesced into a social accountability network which persisted beyond the initial Panama Paper information event and which was re-activated in 2017 when the ICIJ published the Paradise Papers. (shrink)

At the time of the First Crusade, numerous factors fed the tension between the Byzantines and those Western Europeans who traveled through imperial lands. However, one of these factors - the supply of food - is often assumed or taken for granted. The purpose of this article is to examine the impact that the acquisition of food had on relations between the purported allies. It seems that during the First Crusade, at a critical juncture in their ongoing social and political (...) relationship, the supply of food seriously undermined relations between the crusaders and the Byzantines, gravely tarnishing political and military negotiations, and setting a precedent that clouded future interaction. Further, logistical issues appear to shed light on divisions among the social classes, namely, how individuals in the same army, but of different backgrounds, might interpret a similar event in distinctive ways. (shrink)

This study examines the impact of Sarbanes–Oxley on the nonprofit sector. Focusing on three key SOX policies applicable to charities—conflict-of-interest policies, records retention policies, and whistleblower policies—this study tests the relationship between the existence and addition of these policies on subsequent ethical and governance lapses as reflected in the issuance of “donor advisories” by the large third-party ratings agency Charity Navigator. The findings suggest that, controlling for other relevant organizational factors, the three SOX-inspired written policies are related to a reduced (...) likelihood of donor advisories in the organizations rated by Charity Navigator. (shrink)

The male gametes of most organisms lack cytoplasm. Consequently, most cytoplasmic genetic elements are maternally inherited: they cannot be transmitted patrilinnearly. The evolutionary interests of cytoplasmic elements therefore lie in transmission through the female. These elements may thus be in evolutionary conflict with nuclear genes which are transmitted by both sexes. This conflict is manifested in observations of cytoplasmically induced biased sex‐ratios. Some cytoplasmic genes avoid this fate by biasing the primary sex ratio towards females, or by inducing parthenogenesis. Others (...) kill male hosts, and either achieve transmission via dispersal, or benefit their clonal relatives in the dead male's female siblings. Still others cause the failure of zygotes resulting from pairings between males carrying specific microbes and females lacking them, causing an increase in the microbes through the sterilisation of non‐bearing females. Many, but not all, of these ‘ultra‐selfish’ microbes are closely related. Investigations of the significance of their phylogenetic affinities, or lack of them, their adaptability in terms of the methods by which they avoid, or ameliorate, the adverse effects of being in male hosts, and their importance as selective agents in the evolution of invertebrate sex determination systems, provide fertile spheres for future research. (shrink)

This piece, included in the drift special issue of continent. , was created as one step in a thread of inquiry. While each of the contributions to drift stand on their own, the project was an attempt to follow a line of theoretical inquiry as it passed through time and the postal service(s) from October 2012 until May 2013. This issue hosts two threads: between space & place and between intention & attention . The editors recommend that to experience the (...) drifiting thought that attention be paid to the contributions as they entered into conversation one after another. This particular piece is from the BETWEEN SPACE & PLACE thread: April Vannini, Those Between the Common * Laura Dean & Jesse McClelland, Ballard: A Portrait of Placemaking * Amara Hark Weber, Crossroad * Isaac Linder & Berit Soli-Holt, The Call of the Wild: Terro(i)r Modulations * Ashley D. Hairston, Momma taught us to keep a clean house * Sean Smith, The Garage (Take One) * * * * Preface: Variations of Archiving the Anarchive Through Editorial Witnessing by April Vannini “a diagram is a map, or rather several superimposed maps.” 1 What do we do with essays, art, artefacts, and practices that go against, resist, challenge and reject archival capture or documentation since they do not fit within the screen or manage to move beyond conventional scales? What do we do with an essay or artefact that is the event of the event becoming-event itself, or how do we move from volumetric space to two-dimensional space? How do editors, curators, participants, etc. become witness to an anarchive? And most importantly, what are the potential and unanticipated ways in which a volumetric submission can be diagrammed within a two- dimensional space? In short, how do we archive the anarchive? These are questions that have emerged and have been consciously and purposely activated by Sean Smith’s thinkpiece for this issue, The Garage (Take One) . Sean, as part of his contribution to the special issue of drift within the thread in between space and place , created an artefact that emerged out of an event held during May 2013, titled Cottage University: Topology and Immanence . The visual documentation of The Garage (Take One) is not an archive but an anarchive due to its multimodal form, non-representational diagramming, and its reactivation of non-representational folding which animates its non-representational or more-than -representational condition. In short, The Garage (Take One) stymies attempts to be translated into digital text, representationally. As a reader of Sean’s submission you will only have access to a portion of the original submitted contribution (see “Take One”). At this time, I remain the only witness of The Garage (Take One) in its entirety: I was present at the original event, Cottage University: Topology and Immanence , and I was the sole receiver of the original package because of my role as editor for the thread, in between space and place . However, I would like to stress that I was unaware of what Sean would submit as his contribution to the special issue. What is presented here is an emergent rippling of the event that was not predetermined or arranged in advance ... a drifting of sorts! As for now, the artefact sits here on my desk next to a pile of books—folded, creased and somewhat lost in its translation into digital form. Questions of transcribing, translating and converting volumetric space to two-dimensional space have been considered throughout this process. And more importantly this artefact and its processes raise the issue of not what has been saved and included but what has been left out in each conversion of the original into the academic publication. What follows this preface are various “cuts” or “takes” from The Garage: Take One . Each take or cut is merely an interpretive and representational rendering of the original volumetric submission. Although with that said I would like to propose they are more than just representations or interpretations: each take or cut works as rippling variations of the event itself . It is important to acknowledge that much has been lost in the creases and much still lingers which will never be archived within an academic journal. Hence, a discussion of how to archive the anarchive is so crucial to para-academic “scholarship”. I will sum up the process that has emerged from The Garage (Take One) with a final word from Brian Massumi, written in his foreword to Deleuze and Guattari’s A Thousand Plateaus : Each 'plateau' is an orchestration of crashing bricks extracted from a variety of disciplinary edifices. They carry traces of their former emplacement, which give them a spin defining the arc of their vector. The vectors are meant to converge at a volatile juncture, but one that is sustained, as an open equilibrium of moving parts each with its own trajectory. The word 'plateau' comes from an essay by Gregory Bateson on Balinese culture, in which he found a libidinal economy quite different from the West's orgasmic orientation. In Deleuze and Guattari, a plateau is reached when circumstances combine to bring an activity to a pitch of intensity that is not automatically dissipated in a climax. The heightening of energies is sustained long enough to leave a kind of afterimage of its dynamism that can be reactivated or injected into other activities, creating a fabric of intensive states between which any number of connecting routes could exist. 2 The Garage (Take One) Double Take 2:31pm/5:31pm Sean Smith You there? I just wanted to emphasize a couple of things about the process of the submission: 2:31pm/5:31pm April Warn-Vannini Yes, listening. 2:36pm/5:36pm Sean Smith 1.When you describe feeding forward from the CU (Cottage University) event, it is a WALKING ACTIVITY that reinvests/reactivates the intensive energies of the event. that is what my photos are in Take One......it connects the intensive state of CU to my "one-take" writing on construction paper experience. i'm not sure if i adequately conveyed that or not, or if you did, or how important that is. 2. In doing so, it ruptures open the "space" and "place" of material practice ...and how these may enter into the mediated production of academic journal work...and its flattened two-dimensional experience. 3. the abstract machines of CU (i.e.coming out of silence) are invested with a new diagramming practice (the photo walk) to produce a new text that is neither-nor: "spaced" as a content of that walk (garages), but "placed" as a technical question (coming out of silence to language). 4. the new text is precisely diagrammatic, non-representational, anarchival. ....multimodal. ok, that's all that comes to mind right now. appreciating your efforts. 5. oh, finally, i think you might need a better definition of "anarchive" here..... it was hard to pin them down in montreal on what this is, so you wouldn't be wrong, per se, but more require a working definition for the reader. obviously, as you say, without getting too academic/citations, etc. know what i am saying? 2:46pm/5:46pm April Warn-Vannini 1. Totally got it but I think I did because of our many past conversations about how to archive the event 2. Yes this is what I love about this. And I think you speak to this very carefully in your writing on the Garage. Now whether others pick up on this I don't know. This is why I wanted to see what it would look like if I flattened it (take 3). 5. I agree that a better definition is needed. This is where I've been stumbling because I have not found anything that clearly defines what is meant by anarchive. 2:47pm/5:47pm Sean Smith "with take one being the only remainder of the original submission left to reveal...." precisely because of its digitality!!! yeah, i would probably just append an edited version of what we are saying here, as if the editing process was still a ripple of the event. me "adding" new text later i think defeats the purpose, but if you were to take snippets of this dialogue as part of the anarachive/ 2:48pm/5:48pm April Warn-Vannini Totally! 2:49pm/5:49pm Sean Smith and just *use them*, i think that's fair game. that way i won't be crafting my words with intent. you can even use this profile pic. 2:50pm/5:50pm April Warn-Vannini Okay perfect. With that said, do you think I should just discuss your process further in the preface or include an introduction that would be in take one? 2:51pm/5:51pm Sean Smith could it be Take Two in its own right, like an atemporal ripple that coexists with the others and bumps them to Three, Four and Five? Or could it be called "Double Take" and leave the others as Two, Three, Four? 2:53pm/5:53pm April Warn-Vannini Perfect. I like double take 2:53pm/5:53pm Sean Smith and it's us hashing through this discussion 2:53pm/5:53pm April Warn-Vannini Double take will follow take one. i like this. The Garage (Take Two) Folded, taped (scotch and duct), folded recycled chart paper previous emergent thoughts: performed, inscribed and made anew Red jiffy, black jiffy, blue ink pen cursive writing/block writing diagramming amplification dilated » » » » directional arrows « « « « Moistened, torn, crinkled Ruptures Anarchive of thought events Deciphering language/writing Exchanged as a volumetrics of new spaces Performing tactics of “writing off the page” on the page Enclosed [OPEN THE DOORS, MOVE FROM SURFACE TO VOLUME…AND THE CONVERSATION JUST MIGHT BEGIN ANEW. *stamped* SEAN SMITH] Drifting Drifting Drifting The Garage (Take Three) 6 Sean Smith video from April Vannini on Vimeo . The Garage (Take Four) The Garage (Take Five). (shrink)

Supporting Hamilton’s inclusive fitness theory, archival analyses of inheritance patterns in wills have revealed that people invest more of their estates in kin of closer genetic relatedness. Recent classroom experiments have shown that this genetic relatedness effect is stronger for relatives of direct lineage (children, grandchildren) than for relatives of collateral lineage (siblings, nieces, nephews). In the present research, multilevel modeling of more than 1,000 British Columbian wills revealed a positive effect of genetic relatedness on proportions of estates allocated to (...) relatives. This effect was qualified by an interaction with lineage, such that it was stronger for direct than for collateral relatives. Exploratory analyses of the moderating role of benefactors’ sex and estate values showed the genetic relatedness effect was stronger among female and wealthier benefactors. The importance of these moderators to understanding kin investment in modern humans is discussed. (shrink)

A Comparative Dictionary of Raute and Rawat: Tibeto-Burman Languages of the Central Himalayas. By Jana Fortier. Harvard Oriental Series, vol. 88. Cambridge, MA: Harvard University Press, 2019. Pp. xx + 276. $50.

The “therapeutic obligation” is a physician’s duty to provide his patients with what he believes is the best available treatment. We begin by discussing some prominent formulations of the obligation before raising two related considerations against those formulations. First, they do not make sense of cases where doctors are permitted to provide suboptimal care. Second, they give incorrect results in cases where doctors are choosing treatments in challenging epistemic environments. We then propose and defend an account of the therapeutic obligation (...) that solves the problems that undermined previous efforts at formulating the TO. We conclude by considering how apparent problems with our proposal actually rest on difficulties with informed consent. (shrink)

Geography and Ethics examines the place of geography in ethics and of ethics in geography by drawing together specially commissioned contributors from distinguished scholars from around the world.

We used a retrospective survey to model the patterns of appraisal, motivation, and coping that uniquely correspond with 12 positive emotions (affection/love, amusement, awe, challenge/det...

Observing that standard accounts of constitutional law - both the "conservative" and "liberal" varieties - have lost their power to illuminate, The Constitution and the Pride of Reason explores how constitutional law hangs together (and how it falls apart) by investigating the perennial claim that the Constitution and its interpretation somehow embody a commitment to governance by "reason". What does this claim mean, and is it valid? In confronting these queries, Smith offers revealing and iconoclastic assessments of constitutionalists ranging (...) from Madison and Jefferson to Dworkin and Bork. Also detailed in these pages is a provocative overview of the whole constitutional project, from its noble aspirations to its tragic failures. (shrink)

The article discusses the failure of the current positivistic and materialist business ethics paradigms to adequately deal with the enormity of the contemporary business ethics crisis. Citing behavioural research into the linkage between beliefs, values and behaviour, the author suggests spiritual renewal as a solution based on the ‘fallenness’ of mankind and the reality of human evil. The concept of faith, obedience and the resulting ‘kingdom consciousness’ is explored as a basis for spiritual renewal leading to behavioural change. The process (...) of renewal is depicted as a synergistic, mutually supportive relationship between faith and action. (shrink)

The article discusses the failure of the current positivistic and materialist business ethics paradigms to adequately deal with the enormity of the contemporary business ethics crisis. Citing behavioural research into the linkage between beliefs, values and behaviour, the author suggests spiritual renewal as a solution based on the ‘fallenness’ of mankind and the reality of human evil. The concept of faith, obedience and the resulting ‘kingdom consciousness’ is explored as a basis for spiritual renewal leading to behavioural change. The process (...) of renewal is depicted as a synergistic, mutually supportive relationship between faith and action. (shrink)

The paper replies to an earlier paper by Yannis Stephanou, who presented an argument purportedly showing the falsity of certain instances of the characteristic axiom of the modal logic B. The paper argues that the B axiom was not to blame for the unsoundness of Stephanou's argument.