Chromosomal origins of DNA replication in higher eukaryotes differ significantly from those of E. coli (oriC) and the tumor virus, SV40 (ori sequence). Initiation events appear to occur throughout broad zones rather than at specific origin sequences. Analysis of four chromosomal origin regions reveals that they share common modular sequence elements. These include DNA unwinding elements, pyrimidine tracts that may serve as strong DNA polymerase‐primase start sites, scaffold associated regions, transcriptional regulatory sequences, and, possibly, initiator protein binding sites and inherently (...) destabilized regions. Based on the novel organization of chromosomal origin regions, we propose a model for initiation of DNA replication in higher eukaryotes. Unwinding of duplex DNA during initiation may be uncoupled, both temporally and spatially, from DNA synthesis, resulting in transient single‐stranded intermediates that function in lieu of conventional replication forks during chromosomal DNA replication. DNA synthesis begins subsequently at multiple sites Within the unwound regions rather than at specific origin sequences. (shrink)

Given a space in an elementary submodel M of H, define XM to be X∩M with the topology generated by . It is established, using anti-large-cardinals assumptions, that if XM is compact and its regular open algebra is isomorphic to that of a continuous image of some power of the two-point discrete space, then X=XM. Assuming in addition, the result holds for any compact XM satisfying the countable chain condition.

Argumentation as the public exchange of reasons is widely thought to enhance deliberative interactions that generate and justify reasonable public policies. Adopting an argumentation-theoretic perspective, we survey the norms that should govern public argumentation and address some of the complexities that scholarly treatments have identified. Our focus is on norms associated with the ideals of correctness and participation as sources of a politically legitimate deliberative outcome. In principle, both ideals are mutually coherent. If the information needed for a correct deliberative (...) outcome is distributed among agents, then maximising participation increases information diversity. But both ideals can also be in tension. If participants lack competence or are prone to biases, a correct deliberative outcome requires limiting participation. The central question for public argumentation, therefore, is how to strike a balance between both ideals. Rather than advocating a preferred normative framework, our main purpose is to illustrate the complexity of this theme. (shrink)

Due to the COVID-19 pandemic, cities and states adopted social distancing, social isolation, or quarantine measurements to slow the transmission of the disease. Negative mental health outcomes including depression and anxiety have been associated with social distancing or social isolation. The purpose of the present study was to examine changes in psychological health and physical activity over an 8 week period under social distancing policies during the COVID-19 pandemic.Methods: Ninety individuals participated in this study. Qualifying participants answered questions using an (...) online survey regarding their loneliness, depressive symptoms, anxiety symptoms, mood state, and physical activity over four time points each lasting two weeks.Results: Symptoms of depression and state anxiety were increased in the population when compared to nationwide statistics from before the COVID-19 pandemic. Time point 2, ~1 month into social isolation, showed the most significant effects on mental health. During this time point, 100% of the participants showed symptoms of depression. There were no significant changes in physical activity over the 8 weeks. Loneliness, depressive symptoms, fatigue, and mood state were negatively associated with participation in physical activity. Vigor and state anxiety were associated with participation in physical activity.Conclusion: Social isolation and social distancing practices have had a negative effect on depression, anxiety, and mood over time. It appeared that depressive symptoms and total mood disturbance was elevated during time point two. Depressive symptoms were much higher than average compared to previous epidemiological data. Physical activity amount did not change over time but was associated with poor mental health. (shrink)

Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index percentile] and non-obese preteens with different levels of math skill; (...) thirty-one with low math skills and thirty-one with high math skills. No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills. (shrink)

Mentoring Away the Glass Ceiling in Academia: A Cultured Critique describes how women of diverse backgrounds perceive their mentoring experiences or the lack of mentoring experiences in the academy. This book provides a space for envisioning strategies and practices to improve mentoring practices and the collegiate environment.

“I often said before starting, that I had no doubt I should frequently repent of the whole undertaking.” So wrote Charles Darwin aboard The Beagle , bound for the Galapagos Islands and what would arguably become the greatest and most controversial discovery in scientific history. But the theory of evolution did not spring full-blown from the head of Darwin. Since the dawn of humanity, priests, philosophers, and scientists have debated the origin and development of life on earth, and with modern (...) science, that debate shifted into high gear. In this lively, deeply erudite work, Pulitzer Prize–winning science historian Edward J. Larson takes us on a guided tour of Darwin’s “dangerous idea,” from its theoretical antecedents in the early nineteenth century to the brilliant breakthroughs of Darwin and Wallace, to Watson and Crick’s stunning discovery of the DNA double helix, and to the triumphant neo-Darwinian synthesis and rising sociobiology today. Along the way, Larson expertly places the scientific upheaval of evolution in cultural perspective: the social and philosophical earthquake that was the French Revolution; the development, in England, of a laissez-faire capitalism in tune with a Darwinian ethos of “survival of the fittest”; the emergence of Social Darwinism and the dark science of eugenics against a backdrop of industrial revolution; the American Christian backlash against evolutionism that culminated in the famous Scopes trial; and on to today’s world, where religious fundamentalists litigate for the right to teach “creation science” alongside evolution in U.S. public schools, even as the theory itself continues to evolve in new and surprising directions. Throughout, Larson trains his spotlight on the lives and careers of the scientists, explorers, and eccentrics whose collaborations and competitions have driven the theory of evolution forward. Here are portraits of Cuvier, Lamarck, Darwin, Wallace, Haeckel, Galton, Huxley, Mendel, Morgan, Fisher, Dobzhansky, Watson and Crick, W. D. Hamilton, E. O. Wilson, and many others. Celebrated as one of mankind’s crowning scientific achievements and reviled as a threat to our deepest values, the theory of evolution has utterly transformed our view of life, religion, origins, and the theory itself, and remains controversial, especially in the United States (where 90% of adults do not subscribe to the full Darwinian vision). Replete with fresh material and new insights, Evolution will educate and inform while taking readers on a fascinating journey of discovery. (shrink)

Avant le début des années 1990, les héroïnes étaient souvent considérées comme des versions affadies d’une catégorie générique bien plus glorieuse, celle des héros grecs. A la limite l’héroïsme ne se pensait même pas au féminin. Depuis, deux livres ont corrigé la perspective en faisant valoir l’importance des cultes dirigés vers des personnages féminins tout en tentant de souligner les spécificités de ce type d’héroïsme en Grèce ancienne. En choisissant de travailler sur les héroïnes cultuell...

The aim of this dissertation is an analysis of agreement in relation to genitival constructions. It proposes that the Apulian non-prepositional enitives of San Marco in Lamis can be described as regulated by a definiteness agreement mechanism manifesting itself in the necessity of articled heads (excluding vocatives) and genitival nouns, coupled with an adjacency requirement which limits the realization of post-nominal modifiers of the head in a post-genitival position, where they might only refer to the genitive noun. This work thus (...) proposes that such agreement for definiteness is the same holding in Romanian non-al genitives which result in the linker construction when agreement is disrupted. In chapter 1 we thus introduce Kartvelian genitives by Suffixaufnahme which notoriously represent a genitive-head noun morphological agreement phenomenon. Plank (1995) also shows that in a series of genitives, Suffixaufnahme shows up only on the last one, demonstrating that when it comes to agreement in genitives, local dynamics of sorts are often at stake (as it happens with the Costruct State). In 2 we move to linkers; linkers have been connected to agreement in Suffixaufnahme genitives at least since Plank (1995) and later works such as Larson and Yamakido (2006), Manzini et al (2016), and Manzini (2018), according to which linkers can be assimilated to agreement. In fact, in synthetic systems such as Romanian and Aromanian, Albanian and Arbëresh, and Kurdish varieties, linkers agree for φ with either the head or the genitive noun. Giurgea and Dobrovie-Sorin (2013: 126) further show that in Romanian non-linker constructions possessives agree for case with the head noun. In linker constructions, agreement for case is not present: it’s the linker itself which agrees with the head noun, this time for φ. Chapter 3 deals with genitival modification in Hebrew and a number of Arabic varieties. It proposes that the pseudoprepositions found in Arabic varieties are nouns in the Construct State. This was previously proposed for Palestinian Arabic in Mohammad (1999), which also shows that such elements agree for φ with the modified noun. 3.2 takes into account the Semitic preposition l-, dealing with the question of whether this lement can be characterized as possessive and locative as it happens for Romance a. 4 analyzes Apulian non-prepositional genitives and proposes as anticipated that the necessity of articled nouns in the construction is to be linked to an agreement relation taking place via D. Lastly, 5 subsumes the conclusions of this work. (shrink)

This paper investigates the effects of (surface) DP-internal quantifying expressions on semantic interpretation. In particular, I investigate two syntactic constructions in which an adjective takes scope out of its embedding DP, thus raising an interesting question for strict compositionality. Regarding the first construction, I follow Larson (1999) and assume that the adjective incorporates into the determiner of its DP, forming a complex quantifier [D+A]. I present new evidence in favor of this analysis. Since Larson's semantic analysis of complex (...) quantifiers [D+A] makes a wrong prediction, I propose an alternative, empirically more adequate analysis that treats D+A compounds as pluractional quantifiers in the sense of Lasersohn (1995). Finally, I turn to the second construction, arguing that – despite superficial similarities to the first construction - it should not be analyzed in terms of complex quantifier formation, but in terms of LF-movement of the adjective to Spec,DP. The discussion suggests that there is more than one way for DP-internal modifiers to take DP-external scope in natural language. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Imagined Apotheoses: Drake, Harriot, and Ralegh in the AmericasWilliam M. HamlinPerhaps the two best known stories of Europeans being taken for gods by non-European peoples are those of Hernan Cortés in Mexico and Captain James Cook in Hawaii. Separated by two hundred sixty years, five thousand miles, and vast differences in cultural and linguistic context, these two incidents nonetheless share many traits in the conventional telling. Cortés and Cook (...) were both strong leaders, for instance, both capable of inspiring devotion among their subordinates. Both men became amateur ethnographers during their lengthy sojourns away from Europe, both sought to promote an image of respectful rather than rapacious foreign incursion, and both are said to have been taken for returning gods by the native peoples among whom they landed: Cortés for the Toltec culture-hero and demigod Quetzalcoatl, Cook for the Hawaiian deity Lono. Click for larger view View full resolutionFigure 1.“The Far Side” cartoon by Gary Larson. Courtesy of Chronicle Features, San Francisco.Recent scholarly studies and debates—among them the rather strident dispute between Gananath Obeyesekere and Marshall Sahlins over the alleged deification of Cook by eighteenth-century Hawaiians—have opened up these returning-god theories to skeptical critique and detailed justification; but such discussions have had little, if any, impact on popular imagination. 1 [End Page 405] Indeed, the idea that redoubtable European explorers can be (and often are) perceived as supernatural beings by non-European “primitives” has been uncritically perpetuated to this day by filmmakers, fantasists, writers of popular history, and purveyors of cultural literacy. E. D. Hirsch, Jr., for instance, informs our children that Caribbean islanders encountered by Columbus “asked if he had come from heaven”—the implication being, of course, that they took him for a god. 2 And in the recent film, 1492: Conquest of Paradise, we hear the indefatigable Admiral (played by Gerard Depardieu) claim that “on every island the natives welcome us with great generosity and trust.... Because of our appearance, we have been mistaken for gods, and are treated accordingly.” 3 Fortunately, we also have a “Far Side” parody of the cultural conceit on which such ideas in part rely, but the cartoon serves as well to demonstrate just how thoroughly the conceit has permeated our collective awareness (see figure 1). 4 Click for larger view View full resolutionFigure 2.“It’s against my programming to impersonate a deity.” From The Return of the Jedi, dir. Richard Marquand, Lucasfilm, Ltd., 1983. All Rights Reserved. Courtesy of Lucasfilm, Ltd.Let me offer just one other example. Near the end of the popular 1983 film The Return of the Jedi, the forest-dwelling Ewoks begin to chant and salaam upon first glimpsing the golden robot C-3PO, who in turn tells his captured comrades, “I do believe they think I am some sort of god.” When Han Solo sarcastically asks the robot to use his “divine influence” to help extricate them from their predicament, C-3PO replies that such an action would be improper: “It’s against my programming to impersonate a deity.” Here we see, embedded within a film romance, both the classic trope of the apotheosized foreigner and the related motif of the foreigner’s reluctance to [End Page 406] play the god-role (see figure 2). It is worth noting, however, that while C-3PO may be unwilling to exploit the Ewoks’ misperception, Luke Skywalker is not; he uses the “Force” to convince the Ewoks of the robot’s magical prowess and, more to the point, to perpetuate their misapprehension. 5What I wish to suggest in this essay is that certain habitual Western assumptions or conceits regarding cross-cultural encounters—assumptions which have been usefully termed “myth models” inasmuch as they condition human perception and find frequent discursive expression—coexist easily but in fact disjunctively with certain other ideological structures in many early modern travel narratives and colonial accounts. Obeyesekere, in his provocative book on the supposed deification of Captain Cook in Hawaii, has linked such myth models to the conceptual structures of the longue durée as characterized by Fernand Braudel, and it is possible that they may also be... (shrink)

U.S. approaches to oversight of research and technological products have developed over time in an effort to ensure safety to humans, animals, and the environment and to control use in a social context. In modern times, regulatory and oversight tools have evolved to include diverse approaches such as performance standards, tradable allowances, consultations between government and industry, and pre-market safety and efficacy reviews. The decision whether to impose an oversight system, the oversight elements, the level of oversight, the choice of (...) approach, and its execution can profoundly affect technological development, individual and collective interests, and public confidence in technological products. Oversight is conducted by a range of institutions with various capabilities, cultures, and motives. Avenues for disputing oversight decisions are also important, and some argue that the U.S. operates in an adversarial regulatory culture in which Congress, the media, and stakeholders regularly contest the decisions of federal agencies. (shrink)

Originally published in 1936, this book presents the ancient Greek text of the paraphrases and quotations of Zeno's philosophical arguments, together with a facing-page English translation and editorial commentary. Detailed notes are incorporated throughout and a bibliography is also included. This book will be of value to anyone with an interest in Zeno and ancient philosophy.

The subject of the present inquiry is the approach-to-the-truth research, which started with the publication of Sir Karl Popper's Conjectures and Refutations. In the decade before this publication, Popper fiercely attacked the ideas of Rudolf Carnap about confirmation and induction; and ten years later, in the famous tenth chapter of Conjectures he introduced his own ideas about scientific progress and verisimilitude. Abhorring inductivism for its apprecia tion of logical weakness rather than strength, Popper tried to show that fallibilism could serve (...) the purpose of approach to the truth. To substantiate this idea he formalized the common sense intuition about preferences, that is: B is to be preferred to A if B has more advantages andfewer drawbacks than A. In 1974, however, David Millerand Pavel Tichy proved that Popper's formal explication could not be used to compare false theories. Subsequently, many researchers proposed alternatives or tried to improve Popper's original definition. (shrink)

This article describes the process engaged by 17 expert scholars in the development of a set of six consensus recommendations about the normative foundations of pediatric decision-making. The process began with a robust pre-reading assignment, followed by three days of in-person symposium discussions that resulted in a publication in _Pediatrics_ entitled “Pediatric Decision-Making: Consensus Recommendations” (Salter et al. 2023). This article next compares the six recommendations to existing statements about pediatric decision-making (specifically those developed by the American Academy of Pediatrics), (...) highlighting similarities and differences. Finally, the article discusses the value of finding consensus in the field of pediatric bioethics. (shrink)

In this essay, I claim that certain passages in Book IV of Benedict de Spinoza’s Ethics suggest a novel version of what is known as metaethical constructivism. The constructivist interpretation emerges in the course of attempting to resolve a tension between Spinoza’s apparent ethical egoism and some remarks he makes about the efficacy of collaborating with the right partners when attempting to promote our individual self-interest . Though Spinoza maintains that individuals necessarily aim to promote their self-interest, I argue that (...) Spinoza has an atypical conception of self that allows the interests of other people to be partially constitutive of one's own self-interest. In this way, Spinoza can account for the rationality of concern for the interests of others . This interpretation attributes to Spinoza a form of constructivism that differs in important ways from contemporary Humean and Kantian constructivisms and which can in principle be detached from Spinoza’s particular metaphysical commitments in order to yield a third general category of constructivist view . Though my treatment is necessarily brief, it is my hope that it can serve both to motivate a constructivist reading of Spinoza and, perhaps even more crucially, to suggest a Spinozistic variety of constructivism as a live theoretical option in metaethics. (shrink)

Both the concept of a Darwinian tree of life (TOL) and the possibility of its accurate reconstruction have been much criticized. Criticisms mostly revolve around the extensive occurrence of lateral gene transfer (LGT), instances of uptake of complete organisms to become organelles (with the associated subsequent gene transfer to the nucleus), as well as the implications of more subtle aspects of the biological species concept. Here we argue that none of these criticisms are sufficient to abandon the valuable TOL concept (...) and the biological realities it captures. Especially important is the need to conceptually distinguish between organismal trees and gene trees, which necessitates incorporating insights of widely occurring LGT into modern evolutionary theory. We demonstrate that all criticisms, while based on important new findings, do not invalidate the TOL. After considering the implications of these new insights, we find that the contours of evolution are best represented by a TOL. (shrink)

Antimicrobial resistance (AMR) poses an increasing threat to patient care and population health and there is a growing need for novel therapies to tackle AMR. Bacteriophage (phage) therapy is a re-emerging antimicrobial strategy with the potential to transform how bacterial infections are treated in patients and populations. Currently, in the UK, phages can be used as unlicensed medicinal products on a ‘named-patient’ basis. We make an ethical case for why it is crucially important for the UK to invest in Good (...) Manufacturing Practice (GMP) for both ongoing unlicensed and future licensed phage therapy. Access to phages produced to GMP (GMP phages) will ensure effective patient care and better outcomes as well as health systems benefits. The UK also has the potential to become a global leader in the timely and cost-efficient manufacturing and supply of a therapy that meets internationally recognised standards. (shrink)

Shaḥrūr, Muḥammad; Islamic philosophy; Qurʼan; hermeneutics; criticism, interpretation, etc.