In response to DNA‐damage, cells have to decide between different cell fate programmes. Activation of the tumour suppressor HIPK2 specifies the DNA damage response (DDR) and tips the cell fate balance towards an apoptotic response. HIPK2 is activated by the checkpoint kinase ATM, and triggers apoptosis through regulatory phosphorylation of a set of cellular key molecules including the tumour suppressor p53 and the anti‐apoptotic corepressor CtBP. Recent work has identified HIPK2 as a regulator of the ultimate step in cytokinesis: the (...) abscission of the mother and daughter cells. Since proper cytokinesis is essential for genome stability and maintenance of correct ploidy, this finding sheds new light on the tumour suppressor function of HIPK2. Here we highlight the molecular mechanisms coordinating HIPK2 function and discuss its emerging role as a tumour suppressor. (shrink)

Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism (...) of action of the p53 Ser46 phospho‐isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferroptosis still await exploration. In this essay, the current body of evidence on the molecular function of this deadly p53 mark, its evolutionary conservation, and the regulation of the key players of this response, the p53 Serine 46 kinases, are reviewed and dissected. (shrink)

We recognize today's deep neural network (DNN) models of language behaviors as engineering achievements. However, what we know intuitively and scientifically about language shows that what DNNs are and how they are trained on bare texts, makes them poor models of mind and brain for language organization, as it interacts with infant biology, maturation, experience, unique principles, and natural law.

Quine takes physics to be the ultimate arbiter of what there is. [AL 1/29/2004].

As etiologic concepts of diseases gradually changed from humoral to microbial in the 19th century, syphilis presented particularly great challenges to doctors and scientists. Was “syphilis” merely a synonym for “venereal disease,” and did all manifestations attributed to it have the same cause? The discovery in 1879 of the gonococcus by Albert L. Neisser , and of the cause of chancroid, or soft chancre, in 1890 by Augusto Ducrey , established that venereal disease and syphilis were not synonymous, but syphilis (...) continued to mystify investigators. Symptoms could disappear for years and then—in most but not all persons—reappear with entirely different “tertiary” manifestations. .. (shrink)

We show that certain classes of modules have universal models with respect to pure embeddings: Let R be a ring, T a first‐order theory with an infinite model extending the theory of R‐modules and (where ⩽pp stands for “pure submodule”). Assume has the joint embedding and amalgamation properties. If or, then has a universal model of cardinality λ. As a special case, we get a recent result of Shelah [28, 1.2] concerning the existence of universal reduced torsion‐free abelian groups with (...) respect to pure embeddings.We begin the study of limit models for classes of R‐modules with joint embedding and amalgamation. We show that limit models with chains of long cofinality are pure‐injective and we characterize limit models with chains of countable cofinality. This can be used to answer [18, Question 4.25].As this paper is aimed at model theorists and algebraists an effort was made to provide the background for both. (shrink)

As fundamental researchers in the neuroethology of efference copy, we were stimulated by Grush's bold and original synthesis. In the following critique, we draw attention to ways in which it might be tested in the future, we point out an avoidable conceptual error concerning emulation that Grush seems to share with other workers in the field, and we raise questions about the neural correlates of Grush's schemata that might be probed by neurophysiologists.

The ability to effectively prevent smallpox was the greatest medical accomplishment of the first half of the 19th century. From 1838 to 1840, half a century after vaccination was introduced but before it became mandatory in England, data about the general population of England and Wales recorded 70 deaths per million from smallpox; only 180, 900 vaccinations were recorded. In London alone from 1848 to 1852, there were 4, 858 youthful deaths from smallpox, 67% of which occurred during the first (...) five years of life (Simon 1857).In a report to the House of Commons in 1802, Edward Jenner (1749-1823) stated that person-to-person vaccination was a basic principle of his procedure. He gained confidence in it from the case .. (shrink)

Why and how have supply chain codes of conduct diffused among lead firms around the globe? Prior research has drawn on both institutional and stakeholder theories to explain the adoption of codes, but no study has modeled adoption as a temporally dynamic process of diffusion. We propose that the drivers of adoption shift over time, from exclusively nonmarket to eventually market-based mechanisms as well. In an analysis of an original data set of more than 1,800 firms between the years 2006 (...) and 2015, we find that strong nonmarket labor institutions in a firm’s home country are critical to initiating and sustaining the diffusion process. Market mechanisms, such as investor scrutiny and brand risk, emerge as important later. Contrary to prior research, we did not find a significant effect from nongovernmental organization (NGO) pressure. We conclude that markets for corporate social responsibility can and do arise, but only after they are effectuated by nonmarket institutions. (shrink)

Life is a battlefield onto which we are thrown at birth, with only fate and fortune settling upon where we land. Wherever we land, whether it's on the front lines or surrounded by a network of defenses, we are all asking the same question: why are we here? The problem with this question, however, is that we tend to answer it from our own relative positions, and so we all arrive at different conclusions. The many answers we've created have filled (...) the field. They have become banners that are raised high so that we can see and follow them. These banners are always at risk of being toppled though; always at risk of losing their capacity for belief. But then, what if belief is more than a mere by-product of our universal search? What if belief can change the very fabric of this field? That is, what if truth is actually irrelevant, and the only real thing that makes up this battlefield is the belief, and consequently the collective will, which we invest in our answers? (shrink)

Reality is two-fold, composed of the lighted world as revealed in Genesis, and the darker primordiality which preceded it. The illuminated represents that which the human mind can comprehend, manipulate and re-order to its will: a “designed” and mechanical universe of parts. But behind it, in the backspace of reality, remains the darkness. A formless state of pre-creation, the darkness exists as an endless series of intertwining “signatures” – single possibilities waiting to be created in the illuminated forefront of reality. (...) Permitting each and every part of the lighted world to be connected to the rest, it possesses a “design” all of its own. The question is, if we are blind in the dark, how could we ever come to know it? (shrink)

These essays by some of the most prominent figures in linguistics, artificial intelligence, and psychology explore the problems involved in creating a general cognitive science that will treat language, thought, and behavior in an integrated fashion. They address the fundamental questions of the relations between linguistic structures and cognitive processes, between cognitive processes and language behavior, and between language behavior and linguistic structure. Contents: Introduction, Thomas G. Bever (Columbia University), John M. Carroll and Lance A. Miller (IBM Thomas (...) J. Watson Research Center). "Philosophy and "Linguistics: An Outline of Platonist Grammar, Jerrold J. Katz (CUNY). Sense and Reference in a Psychologically Based Semantics, Ray Jackendoff (Brandeis University). Some Thoughts on the Boundaries and Components of Linguistics, Charles J. Fillmore (University of California, Berkeley). Psychology: Approaches to the Study of the Psychology of Language, Walter Kintsch (University of Colorado). Toward An Abstract Performance Grammar, Charles E. Osgood (University of Illinois). Upgrading a Mind, David Premack (University of Pennsylvania). Computational "Models: "Memory, Meaning, and Syntax, Roger Schank (Yale University) and Lawrence Birnbaum (Yale University). Some Inadequate Theories of Human Language Processing, Mitchell P. Marcus (AT&T Bell Laboratories). (shrink)

The tragedies of the past decade have led to an identity crisis among humanitarians. Respecting traditional principles of neutrality and impartiality and operating procedures based on consent has created as many problems as it has solved.

If the Libyan intervention goes well, it will put teeth in the fledgling RtoP doctrine. Yet, if it goes badly, critics will redouble their opposition, and future decisions will be made more difficult. Libya suggests that we can say no more Holocausts, Cambodias, and Rwandas--and occasionally mean it.

Market participants continue to demand greater transparency from boards of directors, yet little is known about the effect of increased transparency on director decisions. Using a sample of practicing board members, our first experiment provides evidence that increased transparency via disclosure may license directors to make more biased decisions. Guided by rich insights provided by these directors, we examine whether considering a company’s ethical values can deter disclosure-induced licensing by activating a morality mindset. In two additional experiments, we find that (...) exposure to a code of conduct that includes an ethics component does not mitigate the licensing effects we observed; however, considering a separate, concise ethics statement does mitigate these effects. Our findings highlight important differences between the code of conduct and ethics statement for decision-making which can help organizations to mitigate adverse effects of disclosure. Implications for users of financial information and regulators are also discussed. (shrink)