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)

"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 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)

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

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)

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)

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)

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.

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)

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 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].

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 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.

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 existentially closed fields with several orderings, valuations, and p-valuations. We show that these structures are NTP2 of finite burden, but usually have the independence property. Mo...

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)

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.

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

We introduce the notion of a w-good \-frame which is a weakening of Shelah’s notion of a good \-frame. Existence of a w-good \-frame implies existence of a model of size \. Tameness and amalgamation imply extension of a w-good \-frame to larger models. As an application we show:Theorem 0.1. Suppose\. If \ = \mathbb {I} = 1 \le \mathbb {I} < 2^{\lambda ^{++}}\)and\is\\)-tame, then\.The proof presented clarifies some of the details of the main theorem of Shelah and avoids using (...) the heavy set-theoretic machinery of Shelah by replacing it with tameness. (shrink)

During replication, the topology of DNA changes continuously in response to well‐known activities of DNA helicases, polymerases, and topoisomerases. However, replisomes do not always progress at a constant speed and can slow‐down and even stall at precise sites. The way these changes in the rate of replisome progression affect DNA topology is not yet well understood. The interplay of DNA topology and replication in several cases where progression of replication forks reacts differently to changes in DNA topology ahead is discussed (...) here. It is proposed, there are at least two types of replication fork barriers: those that behave also as topological barriers and those that do not. Two‐Dimensional (2D) agarose gel electrophoresis is the method of choice to distinguish between these two different types of replication fork barriers. (shrink)

T is stable. We define the notion of meager regular type and prove that a meager regular type is locally modular. Assuming I < 2o and G is a definable abelian group with locally modular regular generics, we prove a counterpart of Saffe's conjecture. Using these results, for superstable T we prove the conjecture of vanishing multiplicities. Also, as a further application, in some additional cases we prove a conjecture regarding topological stability of pseudo-types over Q.

The compliance-based approach and the integrity approach have been the mainstream responses to corporate scandals. This paper proposes that, despite each approach comprising necessary elements, neither offers a comprehensive solution. Compliance and integrity, far from being mutually exclusive, reinforce each other. Working together, in a correct relationship, they build a harmonized system that yields positive synergies and which also advocates prudence. It enables the generation of a culture of compliance that tends to minimize the technical and ethical errors in decision (...) making. In order to explore an applied harmonized approach, we analyze the audit committee, a specific and broadly accepted regulatory instrument. Formed by non-executive members, regulation requires these members to be dedicated, qualified, and independent as a guarantee of efficiency. We show how the compound of those elements produces positive effects in a context of solid governance. We conclude that it is the strong relationship between efficiency and prudence, in the creation of a culture of compliance, which enables the minimization of errors. (shrink)