In bacteria, PriA protein, a conserved DEXH‐type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA‐binding property allows it to recognize and stabilize stalled forks and the structures derived from them. Cells must cope with fork stalls caused by various replication stresses to complete replication of the entire genome. Failure of the stalled fork stabilization process and eventual restart could lead to various forms of genomic instability. The low viability (...) of priA null cells indicates a frequent occurrence of fork stall during normal growth that needs to be properly processed. PriA specifically recognizes the 3′‐terminus of the nascent leading strand or the invading strand in a displacement (D)‐loop by the three‐prime terminus binding pocket (TT‐pocket) present in its unique DNA binding domain. Elucidation of the structural basis for recognition of arrested forks by PriA should provide useful insight into how stalled forks are recognized in eukaryotes. (shrink)

In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in (...) maintaining functional repetitive regions of the genome such as telomeres and centromeres. Break-induced replication and template switching are conserved mechanisms of replication fork restart. They do not cause microsatellite instability in prokaryotes, but promote repeat expansion in eukaryotes. We suggest that TS and BIR persisted in eukaryotes despite their mutagenic potential because they help maintain long repetitive telomeres and centromeres. (shrink)

In billion years of evolution, eukaryotes preserved the chromosome ends with arrays of guanine repeats surrounded by thymines and adenines, which can form stacks of four‐stranded planar structure known as G‐quadruplex (G4). The rationale behind the evolutionary conservation of the G4 structure at the telomere remained elusive. Our recent study has shed light on this matter by revealing that telomere G4 undergoes oscillation between at least two distinct folded conformations. Additionally, tumor suppressor BRCA2 exhibits a unique mode of interaction with (...) telomere G4. To elaborate, BRCA2 directly interacts with G‐triplex (G3)‐derived intermediates that form during the interconversion of the two different G4 states. In doing so, BRCA2 remodels the G4, facilitating the restart of stalled replication forks. In this review, we succinctly summarize the findings regarding the dynamicity of telomeric G4, emphasize its importance in maintaining telomere replication homeostasis, and the physiological consequences of losing G4 dynamicity at the telomere. (shrink)

Replication forks inevitably stall at damaged DNA in every cell cycle. The ability to overcome DNA lesions is an essential feature of the replication machinery. A variety of specialized polymerases have recently been discovered, which enable cells to replicate past various forms of damage by a process termed translesion synthesis. Alternatively, homologous recombination can be used to restart DNA replication across the lesion. Genetic and biochemical studies have shed light on the impact of these two post‐replication repair pathways in (...) bacteria and yeast. In vertebrates, however, a genetic approach to study post‐replication repair has been compromised because many of the genes involved appear to be essential for embryonic development. We have taken advantage of the chicken cell line DT40 to perform a genetic analysis of translesion synthesis and homologous recombination and to characterize genetic interactions between these two pathways in vertebrates. In this article, we aim to summarize our current understanding of post‐replication repair in DT40 in the perspective of bacterial, yeast and mammalian genetics. BioEssays 26:151–158, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds (...) to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. (shrink)

The correct execution of the DNA replication process is crucially import for the maintenance of genome integrity of the cell. Several types of sources, both endogenous and exogenous, can give rise to DNA damage leading to the DNA replication fork arrest. The processes by which replication blockage is sensed by checkpoint sensors and how the pathway leading to resolution of stalled forks is activated are still not completely understood. However, recent emerging evidence suggests that one candidate for a sensor (...) of replication stress is ATR and that, together with a member of RecQ family helicases, Werner syndrome protein (WRN) and MRE11 complex, can collaborate to promote the restarting of DNA synthesis through the resolution of stalled replication forks. Here, we discuss how WRN, the MRE11 complex and the ATR kinase could work together in response to replication blockage to avoid DNA replication fork collapse and genome instability. BioEssays 26:306–313, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

"What can we expect from the study of Chinese philosophy? « In the philosophical systems of the Hindoos and the Chinese there are still hidden treasures, in which the anticipation of scientific discoveries, the results of thousands of years of occidental research, is most striking. Such are the words of Edward von Hartmann, the most famous living German philosopher1. Much labour has been spent in Europe on the Indian Vedanta philosophy, which had such a marked influence on Arthur Schopenhauer. « (...) The Upanishads, says the author of the Parerga and Paralipomena, are the outcome of the highest human wisdom.... They afford the most remunerative and sublime reading possible in this world, which has been the consolation of my life, as it will be that of my death 2. I do not see why the many germs scattered over the vast field of Chinese philosophy should not have a similar fertilizing influence on some philosophical European mind also. The deep impression caused by the Tao-tê-king will support my view. But much work remains to be done before Chinese philosophy will take its proper place in the history of philosophy. The burden of this task lies with us who are living in China and studying her language and literature, for, while great care is bestowed on all her sister languages in Europe and America, Chinese, the oldest of all, but the youngest in the curriculum of our high-schools, is treated as a step-child by public opinion. This paper is meant as a move in the direction just indicated.". (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

pt. 1. Philosophical essays -- pt. 2. Miscellaneous essays.

This work has been selected by scholars as being culturally important and is part of the knowledge base of civilization as we know it. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be (...) preserved, reproduced, and made generally available to the public. To ensure a quality reading experience, this work has been proofread and republished using a format that seamlessly blends the original graphical elements with text in an easy-to-read typeface. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

We compare fork arrow logic, an extension of arrow logic, and its natural first-order counterpart (the correspondence language) and show that both have the same expressive power. Arrow logic is a modal logic for reasoning about arrow structures, its expressive power is limited to a bounded fragment of first-order logic. Fork arrow logic is obtained by adding to arrow logic the fork modality (related to parallelism and synchronization). As a result, fork arrow logic attains the expressive (...) power of its first-order correspondence language, so both can express the same input–output behavior of processes. (shrink)

We argue against some of Reichenbach's claims about causal forks are incorrect. We do not see why the Second Law of Thermodynamics rules out the existence of conjunctive forks open to the past. In addition, we argue that a common effect rarely forms a conjunctive fork with its joint causes, but it sometimes does. Nevertheless, we think there is something to be said for Reichenbach's idea that forks of various kinds are relevant to explaining why we know more about (...) the past than about the future. And entropy turns out to play a role in the explanation, though not the determining role that Reichenbach envisions. (shrink)

For n≥3, define Tn to be the theory of the generic Kn-free graph, where Kn is the complete graph on n vertices. We prove a graph-theoretic characterization of dividing in Tn and use it to show that forking and dividing are the same for complete types. We then give an example of a forking and nondividing formula. Altogether, Tn provides a counterexample to a question of Chernikov and Kaplan.

We prove that a theory T has stable forking if and only if Teq has stable forking.

We consider existentially closed fields with several orderings, valuations, and [Formula: see text]-valuations. We show that these structures are NTP2 of finite burden, but usually have the independence property. Moreover, forking agrees with dividing, and forking can be characterized in terms of forking in ACVF, RCF, and [Formula: see text]CF.

We prove that in theories without the tree property of the second kind (which include dependent and simple theories) forking and dividing over models are the same, and in fact over any extension base. As an application we show that dependence is equivalent to bounded non-forking assuming NTP 2.

We discuss the role of weakly normal formulas in the theory of thorn forking, as part of a commentary on the paper [5]. We also give a counterexample to Corollary 4.2 from that paper, and in the process discuss “theories with selectors.”.

Let Δ be a set of formulas. In this paper we study the following question: under what assumptions on Δ, the concept “a complete Δ-type p over B does not fork over A ⊆ B” behaves well. We apply the results to the structure theory of ω1-saturated models.

The stability theory of first order theories was initiated by Saharon Shelah in 1969. The classification of abstract elementary classes was initiated by Shelah, too. In several papers, he introduced non-forking relations. Later, Shelah [17, II] introduced the good non-forking frame, an axiomatization of the non-forking notion.We improve results of Shelah on good non-forking frames, mainly by weakening the stability hypothesis in several important theorems, replacing it by the almost λ-stability hypothesis: The number of types over a model of cardinality (...) λ is at most λ+.We present conditions on Kλ, that imply the existence of a model in Kλ+n for all n. We do this by providing sufficiently strong conditions on Kλ, that they are inherited by a properly chosen subclass of Kλ+. What are these conditions? We assume that there is a ‘non-forking’ relation which satisfies the properties of the non-forking relation on superstable first order theories. Note that here we deal with models of a fixed cardinality, λ.While in Shelah [17, II] we assume stability in λ, so we can use brimmed models, here we assume almost stability only, but we add an assumption: The conjugation property.In the context of elementary classes, the superstability assumption gives the existence of types with well-defined dimension and the ω-stability assumption gives the existence and uniqueness of models prime over sets. In our context, the local character assumption is an analog to superstability and the density of the class of uniqueness triples with respect to the relation ≼bs is the analog to ω-stability. (shrink)

We study thorn forking and rosiness in the context of continuous logic. We prove that the Urysohn sphere is rosy (with respect to finitary imaginaries), providing the first example of an essentially continuous unstable theory with a nice notion of independence. In the process, we show that a real rosy theory which has weak elimination of finitary imaginaries is rosy with respect to finitary imaginaries, a fact which is new even for discrete first-order real rosy theories.

Why do we have records of the past and not the future? Entropic explanations for this ‘record asymmetry’ have been popular ever since Boltzmann. Foremost amongst these is Albert and Loewer’s account, which explains the record asymmetry using a low-entropy initial macrostate plus an initial probability distribution. However, the details of how this initial state underpins the record asymmetry are not fully specified. In this paper I attempt to plug this explanatory gap in two steps. First, I suggest the record (...) asymmetry is more immediately explained by the ‘fork asymmetry’, which their picture omits. Second, by relating the fork asymmetry to an initial state that’s metaphysically similar to theirs, I clarify how this ultimately underpins the record asymmetry. (shrink)

We study the generic theory of algebraically closed fields of fixed positive characteristic with a predicate for an additive subgroup, called $\mathrm {ACFG}$. This theory was introduced in [16] as a new example of $\mathrm {NSOP}_{1}$ nonsimple theory. In this paper we describe more features of $\mathrm {ACFG}$, such as imaginaries. We also study various independence relations in $\mathrm {ACFG}$, such as Kim-independence or forking independence, and describe interactions between them.

We consider VC-minimal theories admitting unpackable generating families, and show that in such theories, forking of formulae over a model M is equivalent to containment in global types definable over M, generalizing a result of Dolich on o-minimal theories in [4].

Given the sharp distinction that follows from Hume’s Fork, the proper epistemic status of propositions of mixed mathematics seems to be a mystery. On the one hand, mathematical propositions concern the relation of ideas. They are intuitive and demonstratively certain. On the other hand, propositions of mixed mathematics, such as in Hume’s own example, the law of conservation of momentum, are also matter of fact propositions. They concern causal relations between species of objects, and, in this sense, they are (...) not intuitive or demonstratively certain, but probable or provable. In this article, I argue that the epistemic status of propositions of mixed mathematics is that of matters of fact. I wish to show that their epistemic status is not a mystery. The reason for this is that the propositions of mixed mathematics are dependent on the Uniformity Principle, unlike the propositions of pure mathematics. (shrink)

A ternary relation [Formula: see text] between subsets of the big model of a complete first-order theory T is called an independence relation if it satisfies a certain set of axioms. The primary example is forking in a simple theory, but o-minimal theories are also known to have an interesting independence relation. Our approach in this paper is to treat independence relations as mathematical objects worth studying. The main application is a better understanding of thorn-forking, which turns out to be (...) closely related to modular pairs in the lattice of algebraically closed sets. (shrink)

결정론으로부터 비롯되는 도덕적 책임에 대한 회의론에 대처하면서 양립가능론자들과 양립불가능론자들은 서로 다른 자유의 개념을 제시한다. 양립가능론자들에 따르면, 자유는 행위자가 자신의 의지나 행동을 실현하는데 어떤 물리적/심리적 제약이 없는 상태를 의미한다. 필자는 이러한 자유의 개념을 자유에 대한 불구속 모델이라 부른다. 반면 양립불가능론자들에 따르면, 자유롭게 선택하거나 행위한다는 것은 서로 양립불가능한 둘 이상의 행위방식 혹은 선택지가 행위자에게 열려있고 행위자는 그 중 어느 것도 현실화할 수 있다는 것을 의미한다. 필자는 이러한 자유의 개념을 자유에 대한 갈림길 모델이라 부른다. 각 모델의 지지자들에게는 자신이 옹호하는 모델의 자유 개념이 도덕적 (...) 책임 귀속의 근거가 된다는 점을 보여주는 것이 매우 중요하다. 만일 자유에 관한 어떤 이론이 도덕적 책임 귀속의 문제와 설명적으로 무관하다면, 그러한 이론은 성공적이라고 보기 어렵기 때문이다. 우리는 이러한 이론적 요청을 도덕적 책임에 관한 설명적 요청이라 부를 수 있다. 본 논문에서 필자는 앞서 언급한 두 모델이 도덕적 책임에 관한 설명적 요청을 만족하지 못한다는 점을 논증한다. 필자는 전형적인 프랑크푸르트류의 사례를 분석하면서, 갈림길 모델이 왜 이러한 설명적 요청을 만족하지 못하는지를 논의한다. 또한 계층적 자유의지론에 관해 논의하면서 불구속 모델 또한 이 설명적 요청과 관련하여 성공적이지 못하다는 점을 논의한다. 끝으로 필자는 이 두 모델의 난점을 피하기 위해 논리적으로 귀결되는 자유 개념의 모델을 개략적으로 기술한다. (shrink)

Aims and Scope -/- The Vietnamese Social Sciences and Humanities at a Fork in the Road, utilizing an object-oriented structured database on the productivity of Vietnamese researchers, seeks to provide a comprehensive overview of the development of Social Sciences and Humanities in Vietnam from 2008 to 2018. -/- Quan-Hoang Vuong (Ph.D., Université Libre de Bruxelles) is the director of Centre for Interdisciplinary Social Research, Phenikaa University in Hanoi, Vietnam. He is chairman of the Vietnam chapter of the European Association (...) of Science Editors and serves in the NAFOSTED Scientific Council on Basic Research in the Social Sciences and Humanities (2019-2021). Dr. Vuong has published more than 120 academic articles, and book chapters in about 50 refereed journals and books by such publishers as Elsevier, Inderscience, Nature Publishing Group, Springer, Praeger, Wiley, World Scientific, etc. -/- Trung Tran is an Associate Professor of Mathematics Education and works at Vietnam Academy for Ethnic Minorities. He is a member of the Vietnam chapter of The European Association of Science Editors (EASE), a leader of the Vietnamese Science Editors (VSE) Team, and a chairman of Editor's Board of Journal of Ethnic Minorities Research (ISSN: 0866-773X). (shrink)

This book explores the philosophical thought and praxis of Paul B. Thompson, who planted some of the first seeds of philosophy of agriculture and whose work inspires interdisciplinary scholarship in food ethics, biotechnology, and environmental philosophy. Landmark texts such as The Spirit of the Soil, The Agrarian Vision, and From Field to Fork revealed the fertility of food systems for inspiring reflection on our relationships to technology, the land, and one another. Rooted in philosophical traditions ranging from pragmatism to (...) post-phenomenology, Thompson’s work nourishes projects in ethics, epistemology, philosophy of science, and social and political theory, not only in academic philosophy departments but also in the social and natural sciences. This volume collects this diversity of thought in a tour of the many fields of food systems; from theorizing the sustainability of agroecological systems, to appreciating the quotidian practice of agrarian communities, to anticipating the impacts of emerging biotechnology, and to savoring the roles that food plays in forming our identities. Composed by an international crop of scholars working on the future of food ethics, the volume is a vital contribution to scholars and practitioners thinking through our relationships to the food systems that sustain us. (shrink)

The aim of this paper is to challenge libertarian accounts of free will. It is argued that there is an irreconcilable tension between the way in which philosophers motivate the incompatibilist ability to do otherwise and the way in which they formally express it. Potential incompatibilist responses in the face of this tension are canvassed, and it is argued that each response is problematic. It is not claimed that incompatibilist accounts in general are incoherent, but rather that any incompatibilist account (...) that requires that an agent have alternative possibilities at the point of a free action fails. (shrink)

The tuning-fork model of human social cognition, based on the discovery of mirror neurons (MNs) in the ventral premotor cortex of monkeys, involves the four following assumptions: (1) mirroring processes are processes of resonance or simulation. (2) They can be motor or non-motor. (3) Processes of motor mirroring (or action-mirroring), exemplified by the activity of MNs, constitute instances of third-person mindreading, whereby an observer represents the agent's intention. (4) Non-motor mirroring processes enable humans to represent others' emotions. After questioning (...) all four assumptions, I point out that MNs in an observer's brain could not synchronically resonate with MNs in an agent's brain unless they discharged in a single brain in two distinct tasks at different times. Finally, I sketch a conceptualist alternative to the resonance model according to which a brain mechanism active in both the execution and the perception of e.g., the act of grasping is the neural basis of the concept of e.g., grasping. (shrink)

We give a characterisation of forking in the context of simple theories in terms of the fundamental order.

Program synthesis is a process that obtains an efficient program out of a specification, preserving its meaning. Fork algebras have been proposed as an algebraic basis for the construction of a program synthesis environment. These algebras have an expressive power that encompasses that of first order logic, and they are also the right abstraction of the set model that considers programs as partial binary relations; these results make fork algebras a sound and powerful framework for this task.An important (...) step in the software construction process is the correct selection and manipulation of datatypes, because they are a powerful tool - with them modularization is easy, and enhancement of readability and early error detection are obtained. Algebraic datatypes , are an important class of datatypes because their properties are of great relevance in program transformation.The main goals of this work are to provide a general mechanism for defining algebraic datatypes in the framework of fork algebras, and, at the same time, establish a syntax that simplifies the notation for the specifications. (shrink)

We study properties of forking in the classes of all finite models of a complete theory in a finite variable logic. We also study model constructions under the assumption that forking is trivial.

We prove in particular that, in a large class of dp-minimal theories including the p-adics, definable types are dense amongst nonforking types.