It is shown that, relative to Bishop-style constructive mathematics, the boundedness principle BD-N is equivalent both to a general result about the convergence of double sequences and to a particular one about Cauchyness in a semi-metric space.

For an arbitrary finite algebra $\g A = (A, f, 0, 1)$ one defines a double sequence $a(i,j)$ by $a(i,0)\!=\!a(0,j)\! =\! 1$ and $a(i,j) \!= \!f( a(i, j-1) , a(i-1,j) )$.The problem if such recurrent double sequences are ultimately zero is undecidable, even if we restrict it to the class of commutative finite algebras.

In the context of intuitionistic analysis, we consider the set consisting of all continuous functions from [0,1] to such that =0 and =1, and the set consisting of ’s in where there exists x[0,1] such that . It is well-known that there are weak counterexamples to the intermediate value theorem, and with Brouwer’s continuity principle we have . However, there exists no satisfying answer to . We try to answer to this question by reducing it to a schema about intuitionistic (...) decidability that asserts “there exists an intuitionistically enumerable set that is not intuitionistically decidable”. We also introduce the notion of strong Specker double sequence, and prove that the existence of such a double sequence is equivalent to the existence of a function where. (shrink)

A bounded monotone sequence of reals without a limit is called a Specker sequence. In Russian constructive analysis, Church's Thesis permits the existence of a Specker sequence. In intuitionistic mathematics, Brouwer's Continuity Principle implies it is false that every bounded monotone sequence of real numbers has a limit. We claim that the existence of Specker sequences crucially depends on the properties of intuitionistic decidable sets. We propose a schema about intuitionistic decidability that asserts “there exists an (...) intuitionistic enumerable set that is not intuitionistic decidable” and show that the existence of a Specker sequence is equivalent to ED. We show that ED is consistent with some certain well known axioms of intuitionistic analysis as Weak Continuity Principle, bar induction, and Kripke Schema. Thus, the assumption of the existence of a Specker sequence is conceivable in intuitionistic analysis. We will also introduce the notion of double Specker sequence and study the existence of them. (shrink)

Direct Informational Semantics, according to which [X]s represent X if ‘Xs cause [X]s’ is a law, and Fodorian naturalistic semantics both suffer from double disjunctivitis. I argue that robustness, properly construed, characterizes both represented properties and representing symbols: two or more properties normally regarded as non-disjunctive may each be nomologically connected to a non-disjunctive symbol, and two or more non-disjunctive symbols may each be nomologically connected to a property. This kind of robustness bifurcates the so-called disjunction problem into a (...) Represented-Disjunction Problem, of which Fodor was aware, and a Representer-Disjunction Problem, of which he was on the whole oblivious. Fodor fails to solve these problems: his solution to the former, the Asymmetric Dependence Condition, presupposes a successful solution to the latter, while possible responses that Fodor might make to the latter either beg the former or cannot be met or else flout the Naturalistic Requirement and the Atomistic Requirement. Even setting the Representer-Disjunction Problem aside, the Represented-Disjunction Problem does not get solved, because the robustness involving phonological/orthographic sequences guarantees that nothing can meet the Asymmetrical Dependence Condition. Indeed there is a serious problem of individuating phonological/orthographic tokens and types in a manner that satisfies Fodor’s expectations. This is made manifest by the presence of orthographic tokens embedded in larger tokens. (shrink)

Dicer is a key player in microRNA (miRNA) and RNA interference (RNAi) pathways, processing miRNA precursors and doublestranded RNA into ~21-nt-long products ultimately triggering sequence-dependent gene silencing. Although processing of substrates in vertebrate cells occurs in the cytoplasm, there is growing evidence suggesting Dicer is also present and functional in the nucleus. To address this possibility, we searched for a nuclear localization signal (NLS) in human Dicer and identified its C-terminal double-stranded RNA binding domain (dsRBD) as harboring NLS (...) activity. We show that the dsRBD-NLS can mediate nuclear import of a reporter protein via interaction with importins β, 7, and 8. In the context of full-length Dicer, the dsRBD-NLS is masked. However, duplication of the dsRBD localizes the full-length protein to the nucleus. Furthermore, deletion of the N-terminal helicase domain results in partial accumulation of Dicer in the nucleus upon leptomycin B treatment, indicating that CRM1 contributes to nuclear export of Dicer. Finally, we demonstrate that human Dicer has the ability to shuttle between the nucleus and the cytoplasm. We conclude that Dicer is a shuttling protein whose steady-state localization is cytoplasmic. (shrink)

The objective in this paper is to demonstrate the indispensability of Peirce’s double consciousness to foster abductive reasoning, so that internal/external dialogue inform the worthiness of hunches. These forms of dialogue establish a mental give-and-take forum in which novel meanings/effects are particularly highlighted and noticed. Such attentional shifts are compelled by surprising states of affairs within the beholder’s internal, interpretive competencies, or from external factors (pictures, gestural or linguistic performatives). The dialogic nature of these signs pre-forms operations not possible (...) non-dialogically; they command, interrogate, or suggest alterations to established conduct/beliefs in contexts in which propositional/argumentative conflicts are obviated. This inquiry proposes experimental methodologies to measure when double consciousness (via private/inner speech) mediates hypothesis-making. Vygotsky’s conflict of motive at four distinct developmental stages constitutes the foundation for the proposed experiments. Designs draw upon Vygotsky’s ‘double stimulation’ paradigms that force decision-making processes when conflicts of motive surface. Paradigms include forced imitation of one model while ignoring another (imitating bear, not dragon), and altering a visual array to depict logical sequencing accurately (the “Cycles Test”; “The Odd One Out”). These conflicts require children to change their conduct/beliefs to accommodate to atypical states of affairs. (shrink)

The hardest part of replicating a genome is the beginning. The first step of DNA replication (called “initiation”) mobilizes a large number of specialized proteins (“initiators”) that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary (...) of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ring‐shaped helicase onto the DNA double helix. BioEssays 25:1158–1167, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

We refine results of Gannon [6, Theorem 4.7] and Simon [22, Lemma 2.8] on convergence of Morley sequences. We then introduce the notion of eventual $NIP$, as a property of a model, and prove a variant of [15, Corollary 2.2]. Finally, we give new characterizations of generically stable types (for countable theories) and reinforce the main result of Pillay [17] on the model-theoretic meaning of Grothendieck’s double limit theorem.

Through the use of double task conditions, the sequence learning (SL) paradigm offers unique opportunities to study the relationships between learning and attention. In their original study, Nissen & Bullemer (1987) argued that a secondary tone-counting task prevents SL because it exhausts participants’ attentional resources. Other authors have instead suggested that the detrimental effects of tone-counting are due to scheduling conflicts between performing the main and secondary tasks rather than to attentional load. Frensch & Miner (1994), for instance, (...) suggested that the secondary task impairs sequence learning because it lengthens the response-to-stimulus interval (RSI) and hence makes it less likely for relevant contingencies to be represented together in short-term memory, — a condition for learning. Stadler (1995), on the other hand, argued that the secondary task introduces variability in the RSI and disrupts the organization of the sequence into chunks. Further, according to Willingham, Greenberg & Cannon Thomas (1997) manipulation of the RSI influences performance but not sequence learning.. (shrink)

It has been recently demonstrated that yeast cells are able to partially regress chromosome segregation in telophase as a response to DNA double‐strand breaks (DSBs), likely to find a donor sequence for homology‐directed repair (HDR). This regression challenges the traditional concept that establishes anaphase events as irreversible, hence opening a new field of research in cell biology. Here, the nature of this new behavior in yeast is summarized and the underlying mechanisms are speculated about. It is also discussed (...) whether it can be reproduced in other eukaryotes. Overall, this work brings forwards the need of understanding how cells attempt to repair DSBs when transiting the latest stages of mitosis, i.e., anaphase and telophase. (shrink)

This article looks at the way Matthew Weiner deploys double vision in his historical re-imagination of the 1960s in Mad Men. At issue is both the way the past haunts the present on the diegetic level in the form of flashback sequences, as well as the way Weiner performs simultaneity by virtue of parallel editing, especially in the closing sequences of individual episodes. At issue also is the way stock footage of key historical events such as the moon landing (...) is deployed so as to offer a further juxtaposition of present and past. (shrink)

Central to aesthetic experience, but also to experience in general, is the phenomenon of ‘seeing as'. We see a painting as a landscape, we hear sequence of sounds as a melody, we see a wooden contraption as a boat, and we hear a comment as an insult. There are interesting and important differences between these cases of ‘seeing as': the painting cannot literally be a landscape while the wooden contraption can literally be a boat; a failure to hear sounds (...) as a melody may count as a shortcoming whereas the failure to hear a comment as an insult may be admirable. Here I want to focus mainly on their similarities, however -- similarities that will lead us back to Kant, and to the nature of consciousness itself. The phenomenon of ‘seeing as’ presents certain familiar puzzles: how is seeing a painting as a landscape different from seeing a landscape, on the one hand, and from thinking of the painting as a landscape, on the other? ‘Seeing as’ is not the same as misperceiving, nor is it the same as offering an interpretation, yet it seems related to both. These puzzles are articulated in Section I, and some candidate solutions are rejected. Section II develops a Kantian account of experience showing how the convergence of conflicting representations, achieved through imaginative syntheses, is essential to the experience of objects and to consciousness itself. Kant's insights are used to evaluate some recent responses to the so-called ‘binding problem’ -- the problem of explaining how the contents of consciousness are bound together, and the role of the imagination is further detailed. Section III then returns to the difference between ordinary seeing and ‘seeing as', offering an explanation of the latter in terms of the framework developed in Section II. (shrink)

We consider iterations of general elementary embeddings and, using this notion, point out helices of consistency-wise implications between large large cardinals.Up to now, large cardinal properties have been considered as properties which cannot be accessed by any weaker properties and it has been known that, with respect to this relation, they form a proper hierarchy. The helices we point out significantly change this situation: the same sequence of large cardinal properties occurs repeatedly, changing only the parameters.As results of our (...) investigation of this helical structure, we have new characterizations of extendible cardinals and of Vopěnkan cardinals in terms of elementary embeddings from the universe V, a new large large cardinal property which looks like Shelahness properly between Vopěnkaness and almost hugeness, and a more direct relation between Vopěnkaness and Woodinness than already known.We also consider limits of the helices and relations with the axioms I1–I3. (shrink)

I defend the doctrine of double effect and a so-called ‘strict’ definition of intention: A intends an effect if and only if A has it as an end or believes that it is a state of affairs in the causal sequence that will result in A's end. Following Kamm's proposed ‘doctrine of triple effect’, I distinguish an intended effect from an effect that motivates an action, and show that this distinction is morally significant. I use several contrived cases (...) as illustrations, but my position does not depend on intuitive judgements about them. Instead, it follows from the view that the moral permissibility of an action depends at least partly on how it forms the agent's character. I also respond to some objections presented by Harris, Bennett, McIntyre, Thomson and Scanlon to the doctrine of double effect. (shrink)

RNA polymerase II is recruited to DNA double‐strand breaks (DSBs), transcribes the sequences that flank the break and produces a novel RNA type that has been termed damage‐induced long non‐coding RNA (dilncRNA). DilncRNAs can be processed into short, miRNA‐like molecules or degraded by different ribonucleases. They can also form double‐stranded RNAs or DNA:RNA hybrids. The DNA:RNA hybrids formed at DSBs contribute to the recruitment of repair factors during the early steps of homologous recombination (HR) and, in this way, (...) contribute to the accuracy of the DNA repair. However, if not resolved, the DNA:RNA hybrids are highly mutagenic and prevent the recruitment of later HR factors. Here recent discoveries about the synthesis, processing, and degradation of dilncRNAs are revised. The focus is on RNA clearance, a necessary step for the successful repair of DSBs and the aim is to reconcile contradictory findings on the effects of dilncRNAs and DNA:RNA hybrids in HR. (shrink)

During a call, telemarketers sometimes solicit respondent’s opinions about a product or service. This turns out to be a query with multiple implications, and respondents are alive to them. On the one hand, the recipient orients to a local preference to evaluate the telemarketer’s product positively. On the other hand, a positive assessment may result in expectations and commitments that survive the sequence and that are relevant for the call’s outcome. The recipient is faced with two types of preference (...) structures, one grounded in the sequence and the other one in the course of action it is part of. The preferences may be incompatible. Analysis shows that the shape of response turns with congruent preferences is observably different from response turns with cross-cutting preferences. In the latter case, the dispreferred character of the response to the caller’s ultimate purpose – that is, making a proposal for a commercial transaction – dominates over the response to the opinion query as just an opinion query in its own right. To generalize, the analysis shows that preparatory sequences in standardized courses of action in institutional settings are a special type of presequence. The participants develop a course of action through ordered series of preparatory sequences. Although locally responding to initiatives of the interlocutor, each response shows an orientation to both the local contingencies of the ongoing sequence and to the overall course of action it is contributing to. (shrink)

Many innate immune response proteins recognize foreign nucleic acids from invading pathogens to initiate antiviral signaling. These proteins mostly rely on structural characteristics of the nucleic acids rather than their specific sequences to distinguish self and nonself. One feature utilized by RNA sensors is the extended stretch of double‐stranded RNA (dsRNA) base pairs. However, the criteria for recognizing nonself dsRNAs are rather lenient, and hairpin structure of self‐RNAs can also trigger an immune response. Consequently, aberrant activation of RNA sensors (...) has been reported in numerous human diseases. Yet, in most cases, the activating antigens remain unknown. Recent studies have developed sequencing techniques tailored to specifically capture dsRNAs and identified that various noncoding elements in the nuclear and the mitochondrial genome can generate dsRNAs. Here, the identity of endogenous dsRNAs, their recognition by dsRNA sensors, and their implications in the pathogenesis of human diseases ranging from inflammatory to degenerative are presented. (shrink)

This book summarizes the intense research that the author performed for his Ph.D. thesis , revised and with the addition of an intuitionistic critique of Husserl's concept of number. His starting point consisted of a double conviction: 1) Brouwerian intuitionism is a valid way of doing mathematics but is grounded on a weak philosophy; 2) Husserlian phenomenology can provide a suitable philosophical ground for intuitionism. In order to let intuitionism and phenomenology match, he had to solve in general two (...) problems: 1) the question of the reciprocal indifference that the authors had toward each other's theorizing which indeed they knew; 2) Husserl's general attitude of accepting classical mathematics, which contrasts with the critical attitude of the intuitionists.Moreover, in the specific case focused on by this book—concerning choice sequences, that is, sequences that can be completely lawless and that were admitted as mathematical entities by Brouwer—van Atten had to handle a further problem: such sequences do not fit the characteristic of omnitemporality that the late Husserl seemed to consider a necessary attribute of entities if they were to be considered mathematical. In as far as they are lawless we cannot predict at any moment how they will develop in the future, hence they are not determined at any particular time—they will be determined only in the future.Let us begin with van Atten's first conviction, i.e., that Brouwerian intuitionism is grounded on a weak philosophy. We have to recall that Brouwer provided a mystical attitude for proposing his intuitionism: man can obtain happiness only by keeping himself closed inside the inner Self. Any attempted movement towards the exterior world is a source of pain: in particular language and the sciences. Mathematics, in order to be morally acceptable …. (shrink)

A world product time series covering two million years is well fit by either a sum of four exponentials, or a constant elasticity of substitution (CES) combination of three exponential growth modes: “hunting,” “farming,” and “industry.” The CES parameters suggest that farming substituted for hunting, while industry complemented farming, making the industrial revolution a smoother transition. Each mode grew world product by a factor of a few hundred, and grew a hundred times faster than its predecessor. This weakly suggests that (...) within the next century a new mode might appear with a doubling time measured in days, not years. (shrink)

Two mechanisms are available for the repair of DNA double‐strand breaks (DSBs) in eukaryotic cells: homology directed repair (HDR) and non‐homologous end‐joining (NHEJ). While NHEJ is not restricted to a particular phase of the cell cycle, it is incapable of accurately repairing DBSs that have suffered a loss or gain of nucleotide sequence information. In contrast, HDR achieves accurate repair of such DSBs by use of a sister chromatid as a DNA template, but is restricted to cell cycle (...) phases (S/G2) when such templates are available. In this scheme, G1 cells appear to lack a mechanism for the accurate repair of certain DSBs, and an ability to use alternative templates would be highly advantageous. Considered here, therefore, is the possibility that RNA transcripts are used as templates for HDR. Potential mechanisms for transcript‐templated HDR, and ways in which it might be detected, are presented. BioEssays 28:78–83, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

I will begin by distinguishing between three logics or tendencies in modernity: the logic of technology, the logic of the functional allocation of social positions, and the logic of political power. This conception of three logics or developmental tendencies suggests that the modern world is heterogeneous. Each logic, as it exists potentially, contains within it more than one option. The development itself excludes certain options either forever, or merely for the present. If there were one logic, fewer and fewer potentialities (...) would present themselves in time, and the unfolding of the potentialities would become narrower and increasingly unilinear. However, if there is not only one logic, but three, and if they are relatively although not entirely independent, then the selection of one logic from the three possiblities is not just an internal matter because the environment is essential in the process of eliminating certain possibilities and letting others evolve more forcefully. A category cannot develop possibilities other than the ones which lie dormant in it at the moment of its conception. In this respect the development of each of the logics of modernity is self-propelling. Yet, which of the possiblities will be selected and which of them eliminated—for the short-term or long-term—is not written on the body of the category as it exists potentially. I may add, that even if the evolution of one of the constituents is thwarted for only an historically insignificant time, its character will be different, and this may influence the other logics in a different manner. This is why it would be foolish to think of the developmental logics in teleological terms. Of course, retrospectively, one can establish a teleological sequence, but this would prove only the one thing we already know: that all categories can develop out of themselves only those realities which exist in a state of slumber during their coming-into-being. (shrink)

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non‐endosteal perisinusoidal niche. Single‐cell molecular profiling and in vivo cell lineage analyses play key roles in (...) discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor‐making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast‐chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell‐like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation. (shrink)

This paper discusses the reception of Frankfurt School critical theory in Communist Romania. After some opening remarks concerning the relevance of this topic, Section 2 sketches the evolving political and historical contexts that circumscribed this philosophical reception. The content and configuration of the Romanian reception of critical theory is then discussed in a double sequence: first (Section 3), by surveying and analysing the main clusters of arguments developed in these texts, which are filtered and classified into four categories: (...) a) general considerations and strategic approach to critical theory; b) positive assessments; c) philosophical critiques; d) politico-practical critiques. Then, Section 4 attempts to delineate the divergent paths adumbrated in this field of critical reception, which it illustrates through the specific authorial trajectories of the main Romanian interpreters (Tertulian, Marga and Tismăneanu). Finally, the concluding remarks are devoted to some brief comparative and historical considerations on the meaning, value and amplitude of this critical reception. (shrink)

The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.

Certain sequences of double‐helical DNA can be recognized and tightly bound by oligonucleotides. The effects of such triple‐helical structures on DNA binding proteins have been studied. Stabilities of DNA triple‐helices at or near physiological conditions are sufficient to inhibit DNA binding proteins directed to overlapping sites. Such proteins include restriction endonucleases, methylases, transcription factors, and RNA polymerases. These and Other results suggest that oligonucleotide‐directed triple‐helix formation could provide the basis for designing artificial gene repressors. The general question of whether (...) biological systems employ RNA molecules for recognition and regulation of double‐helical DNA is discussed. (shrink)

This monograph investigates the temporal interpretation of narrative discourse in two parts. The theme of the first part is narrative progression. It begins with a case study of the adverb ‘now’ and its interaction with the meaning of tense. The case study motivates an ontological distinction between events, states and times and proposes that ‘now’ seeks a prominent state that holds throughout the time described by the tense. Building on prior research, prominence is shown to be influenced by principles of (...) discourse coherence and two coherence principles, NARRATION and RESULT, are given a formally explicit characterization. The key innovation is a new method for testing the definitional adequacy of NARRATION and RESULT, namely by an abductive argument. This contribution opens a new way of thinking about how eventive and stative descriptions contribute to the perceived narrative progression in a discourse. -/- The theme of the second part of the monograph is the semantics and pragmatics of tense. A key innovation is that the present and past tenses are treated as scalar alternatives, a view that is motivated by adopting a particular hypothesis concerning stative predication. The proposed analysis accounts for tense in both matrix clauses and in complements of propositional attitudes, where the notorious double access reading arises. This reading is explored as part of a corpus study that provides a glimpse of how tense semantics interacts with Gricean principles and at-issueness. Several cross-linguistic predictions of the analysis are considered, including their consequences for the Sequence of Tense phenomenon and the Upper Limit Constraint. Finally, a hypothesis is provided about how tense meanings compose with temporal adverbs and verb phrases. Two influential analysis of viewpoint aspect are then compared in light of the hypothesis. (shrink)

Large deletions and genomic re‐arrangements are increasingly recognized as common products of double‐strand break repair at Clustered Regularly Interspaced, Short Palindromic Repeats ‐ CRISPR associated protein 9 (CRISPR/Cas9) on‐target sites. Together with well‐known off‐target editing products from Cas9 target misrecognition, these are important limitations, that need to be addressed. Rigorous assessment of Cas9‐editing is necessary to ensure validity of observed phenotypes in Cas9‐edited cell‐lines and model organisms. Here the mechanisms of Cas9 specificity, and strategies to assess and mitigate unwanted (...) effects of Cas9 editing are reviewed; covering guide‐RNA design, RNA modifications, Cas9 modifications, control of Cas9 activity; computational prediction for off‐targets, and experimental methods for detecting Cas9 cleavage. Although recognition of the prevalence of on‐ and off‐target effects of Cas9 editing has increased in recent years, broader uptake across the gene editing community will be important in determining the specificity of Cas9 across diverse applications and organisms. (shrink)

Small tandem DNA duplications in the range of 15 to 300 base‐pairs play an important role in the aetiology of human disease and contribute to genome diversity. Here, we discuss different proposed mechanisms for their occurrence and argue that this type of structural variation mainly results from mutagenic repair of chromosomal breaks. This hypothesis is supported by both bioinformatical analysis of insertions occurring in the genome of different species and disease alleles, as well as by CRISPR/Cas9‐based experimental data from different (...) model systems. Recent work points to fill‐in synthesis at double‐stranded DNA breaks with complementary sequences, regulated by end‐joining mechanisms, to account for small tandem duplications. We will review the prevalence of small tandem duplications in the population, and we will speculate on the potential sources of DNA damage that could give rise to this mutational signature. With the development of novel algorithms to analyse sequencing data, small tandem duplications are now more frequently detected in the human genome and identified as oncogenic gain‐of‐function mutations. Understanding their origin could lead to optimized treatment regimens to prevent therapy‐induced activation of oncogenes and might expose novel vulnerabilities in cancer. (shrink)

Cells mitigate the detrimental consequences of DNA damage on genome stability by attempting high fidelity repair. Homologous recombination templates DNA double‐strand break (DSB) repair on an identical or near identical donor sequence in a process that can in principle access the entire genome. Other physiological processes, such as homolog recognition and pairing during meiosis, also harness the HR machinery using programmed DSBs to physically link homologs and generate crossovers. A consequence of the homology search process by a long (...) nucleoprotein filament is the formation of multi‐invasions (MI), a joint molecule in which the damaged ssDNA has invaded more than one donor molecule. Processing of MI joint molecules can compromise the integrity of both donor sites and lead to their rearrangement. Here, two mechanisms for the generation of rearrangements as a pathological consequence of MI processing are detailed and the potential relevance for non‐allelic homologous recombination discussed. Finally, it is proposed that MI‐induced crossover formation may be a feature of physiological recombination. (shrink)

The article analyzes the problem of Ukraine's development since independence. A comparison of the way of organizing social reality in modern Ukraine and in the Soviet period is carried out. The main regulatory factor in the life of Soviet society was the principle of domination. Ukraine has inherited the principle of domination and retains its leading role in the current social order. Its various manifestations that determine the structure of Ukrainian society, in particular the growth of the bureaucratic class and (...) bureaucratic pressure on all spheres and sections of life, are analyzed. The dominance of bureaucracy contains latent violence, feeds corruption and minimizes social dynamics. It is also a phenomenon of power rent, which finds its expression in a kind of "privatization of the state." Another universal effect of the principle of domination is the doubling of social reality into apparent and hidden. The apparent reality becomes a space for the existence of ordinary citizens and the implementation of legal procedures, while the hidden one contains a system of real circulation of power, which is not regulated by any legal regulations, instead, controls all movements of the social body. The systemic role in the hidden society is played by cliques — informal groups of influential people who really control the course of events. The con- sequence of the principle of domination is the passivity and marginalization of the Ukrainian citizen, associated with the defect of political participation. Such non-participation in power is embodied in such forms of consciousness as hope, liking, and despair. Today, independence is not a given, but a chance that must be realized. The way to this is through the restoration of the role of the people as a sovereign power and the development of non-dominant regulatory factors of sociality. (shrink)

This paper is a contribution toward developing a theory of expansions of semi-Heyting algebras. It grew out of an attempt to settle a conjecture we had made in 1987. Firstly, we unify and extend strikingly similar results of [ 48 ] and [ 50 ] to the (new) equational class DHMSH of dually hemimorphic semi-Heyting algebras, or to its subvariety BDQDSH of blended dual quasi-De Morgan semi-Heyting algebras, thus settling the conjecture. Secondly, we give a criterion for a unary expansion (...) of semi-Heyting algebras to be a discriminator variety and give an algorithm to produce discriminator varieties. We then apply the criterion to exhibit an increasing sequence of discriminator subvarieties of BDQDSH . We also use it to prove that the variety DQSSH of dually quasi-Stone semi- Heyting algebras is a discriminator variety. Thirdly, we investigate a binary expansion of semi-Heyting algebras, namely the variety DblSH of double semi-Heyting algebras by characterizing its simples, and use the characterization to present an increasing sequence of discriminator subvarieties of DblSH . Finally, we apply these results to give bases for “small” subvarieties of BDQDSH , DQSSH , and DblSH. (shrink)

In this contribution, we analyse the treatment of professional practice in two training sequences dedicated to the teaching of written French. Firstly, we examine the characteristics of the training devices organised with a combination of school field and training institution scheme. We then focus on interactions between trainer and trainees within two training activities aimed at sharing and reflecting on practicum. The interest of this double perspective lies in the understanding of knowledge circulation between school field and training institution (...) and how this circulation serves the development of teachers’ action. (shrink)

In eukaryotes, double‐stranded RNAs (dsRNAs) or short, interfering dsRNAs (siRNAs) can reduce the accumulation of a sequence‐related mRNA, often resulting in a loss‐of‐function phenotype—a process termed RNA interference (RNAi). Unfortunately, some mRNAs are resistant to the effects of dsRNA. Experiments designed to unravel RNAi mechanisms in Caenorhabditis elegans have led to the identification of two worm proteins, RRF‐31,2 and, now, ERI‐1,3 that can inhibit RNAi responses. Animals defective in either protein can display enhanced RNAi phenotypes for mRNAs that (...) were previously resistant to dsRNA. Since ERI‐1 is a conserved protein, development of procedures to enhance RNAi effectiveness in other systems may be possible. BioEssays 26:715–718, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The UK’s 100,000 Genomes Project has the aim of sequencing 100,000 genomes from UK National Health Service (NHS) patients while concomitantly transforming clinical care such that whole genome sequencing becomes routine clinical practice in the UK. Policymakers claim that the project will revolutionize NHS care. We wished to explore the 100,000 Genomes Project, and in particular, the extent to which policymaker claims have helped or hindered the work of those associated with Genomics England – the company established by the Department (...) of Health to deliver the project. We interviewed 20 individuals linked to, or working for Genomics England. Interviewees had double-edged views about the context within which they were working. On the one hand, policymakers’ expectations attached to the venture were considered vacuous “genohype”; on the other hand, they were considered the impetus needed for those trying to advance genomic research into clinical practice. Findings should be considered for future genomes projects. (shrink)

In plants, virus‐derived double‐stranded RNA is processed into small interfering (si)RNAs by RNAse III‐type enzymes. siRNAs are believed to guide an RNA‐induced silencing complex (RISC) to promote sequence‐specific degradation (or ‘slicing’) of homologous viral transcripts. This process, called RNA silencing, likely involves Argonaute (AGO) proteins that are known components of plant and animal RISCs. Plant viruses commonly counteract the silencing immune response by producing suppressor proteins, but the molecular basis of their action has remained largely unclear. A recent (...) study by Zhang and colleagues1 now shows that the 2b suppressor of Cucumber mosaic virus directly interacts with Arabidopsis AGO1 and inhibits its slicing activity, suggesting that AGO1 might be a component of the elusive plant antiviral RISC. BioEssays 29:319–323, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

What happens when machines become more intelligent than humans? One view is that this event will be followed by an explosion to ever-greater levels of intelligence, as each generation of machines creates more intelligent machines in turn. This intelligence explosion is now often known as the “singularity”. The basic argument here was set out by the statistician I.J. Good in his 1965 article “Speculations Concerning the First Ultraintelligent Machine”: Let an ultraintelligent machine be defined as a machine that can far (...) surpass all the intellectual activities of any man however clever. Since the design of machines is one of these intellectual activities, an ultraintelligent machine could design even better machines; there would then unquestionably be an “intelligence explosion”, and the intelligence of man would be left far behind. Thus the first ultraintelligent machine is the last invention that man need ever make. The key idea is that a machine that is more intelligent than humans will be better than humans at designing machines. So it will be capable of designing a machine more intelligent than the most intelligent machine that humans can design. So if it is itself designed by humans, it will be capable of designing a machine more intelligent than itself. By similar reasoning, this next machine will also be capable of designing a machine more intelligent than itself. If every machine in turn does what it is capable of, we should expect a sequence of ever more intelligent machines. This intelligence explosion is sometimes combined with another idea, which we might call the “speed explosion”. The argument for a speed explosion starts from the familiar observation that computer processing speed doubles at regular intervals. Suppose that speed doubles every two years and will do so indefinitely. Now suppose that we have human-level artificial intelligence 1 designing new processors. Then faster processing will lead to faster designers and an ever-faster design cycle, leading to a limit point soon afterwards. The argument for a speed explosion was set out by the artificial intelligence researcher Ray Solomonoff in his 1985 article “The Time Scale of Artificial Intelligence”.1 Eliezer Yudkowsky gives a succinct version of the argument in his 1996 article “Staring at the Singularity”: “Computing speed doubles every two subjective years of work.. (shrink)

In selecting the papers for this volume I have excluded all physics papers proper. I have further omitted all book rev.iews. Instead, I have included two papers not published previously; they are marked by an asterisk (*) in the table of contents. Since many of the papers were occasioned by Symposia or similar gatherings their chronological order is rather accidental. Hence I have tried to group the papers thematically into four parts. Within each part the order of sequence is (...) from the more general to the more special, or from a more popular to a more technical treatment. The same principle has been applied to the sequential order of the parts. The foundational papers on quantum mechanics have been arranged in a somewhat dif ferent manner. Chapters XVI-XIX are concerned with the logic of complementarity while in Chapters XX-XXII a more radical recon ceptualization is carried out. Two of the older papers (Chapters VI and VIII) have been revised to bring them more into line with present terminology. Other papers have been corrected by additions and omissions. Additions are marked by square brackets [ ], while double square brackets [[ II signify omis sions or parts to be omitted. Hence [[A]] [B] means that 'A' should be replaced by 'B'. The heading of one paper (Chapter XX) has been changed to make it more descriptive. (shrink)

In this paper I will discuss a rather recondite phenomenon in the area of sequence of tense (SOT), exhibited by sentences like (1): (1) John said that Mary is pregnant. According to traditional grammar, this is a sentence where sequence of tense has failed to apply (i.e., concord has been broken): standard sequence of tense rules would dictate use of a past tense when embedding an event contemporaneous to the embedding verb under a past tense verb, giving (...) the sentence John said that Mary was pregnant. For some verbs breaking concord is impossible (*Mary said that John builds a house) or can only have a present-as-future interpretation (John said that the last spaceship to Mars leaves tomorrow), but with stative verbs, as En¸c (1987) and others have observed, this failure of sequence of tense to apply is associated with a rather special meaning, which we will try to elucidate below. For the moment, let us merely observe that the use of present tense seems to cause such sentences to end up saying something about a larger interval including both the time of utterance and the time of the event described in the main clause. For this reason En¸c calls them “double access sentences”, but that seems a rather dubious name as the interpretation seems to rely on evaluation at a large interval, not just at two points. (shrink)

In this paper I introduce and develop an approach to tenses and temporal expressions that is a mix between eternalism and temporalism consisting in appeal to ‘variadic operators’. The type of variadic operator I will be concerned with is the expansive variadic operator, which takes as input predicates of a certain adicity and yields new predicates with one additional degree of adicity. Appeal to variadic operators has proven useful in giving the semantics of several types of expressions: adverbs ), prepositional (...) phrases ), relational terms ), etc. The focus of this paper is on tenses and temporal expressions, with the aim of showing how these are treated by appeal to temporal variadic operators. First I define the temporal variadic operator and then show how it can be used to account for simple tensed sentences. I also give a rough sketch of how it can accommodate more complex phenomena like sequence of time, interaction between tenses and temporal adverbials, temporal anaphora, later-than-matrix and double-access readings, etc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:The Father’s Will: Christ’s Crucifixion and the Goodness of God by Nicholas E. Lombardo, O.P.Roger W. NuttThe Father’s Will: Christ’s Crucifixion and the Goodness of God. By Nicholas E. Lombardo, O.P. Oxford: Oxford University Press, 2013. Pp. ix + 270. $99.00 (cloth). ISBN: 978-0-19-968858-6.The centrality that Christ’s death by crucifixion has in Christian life, doctrine, and culture is scarcely in need of elaboration. Nevertheless, the relation between the (...) will of the Father and the violent and humiliating manner of Christ’s death raises substantive questions concerning the internal coherence of Christian claims about the love, goodness, and justice of God. In The Father’s Will: Christ’s Crucifixion and the Goodness of God, Nicholas E. Lombardo, O.P., confronts these questions, openly acknowledging their difficulty and seriousness, and provides a philosophically precise and theologically fresh response to the challenges they pose to the credibility of the Christian message.The ten chapters of The Father’s Will are divided into tripartite units that progress in logical sequence from “philosophical prolegomena” (part 1) to “New Testament evidence” (part 2), culminating with a “theological [End Page 317] evaluation” (part 3). The question at the heart of the book is how to reconcile the Christian doctrine that God and evil are incompatible with the theology of the Cross, which seems to require that God’s will is implicated in the evil actions that bring about Christ’s death.The first five chapters (part 1) provide a philosophical analysis of intention (chap. 1), value and obligation (chap. 2), double-effect reasoning (chap. 3), the ethical problems associated with self-sacrifice (chap. 4), and God’s will in relation to the crucifixion (chap. 5). Drawing on his analysis of intention and employing the principle of double effect, Lombardo establishes that it is not necessary to conclude that God wills the evils that are attendant on Christ’s death. “Actions performed by rational intentions,” Lombardo explains, “are not only intended; they are also willed. Rational intending implies rational choice, and rational choice is an act of the will” (32). This understanding of intention and willing, as distinguishable from intentional action, provides a foundation upon which the moral goodness of actions can be determined. “For an action to be good,” Lombardo argues, “it must do more than simply advance our natural inclinations: it must also avoid frustrating them. Only actions that both advance our natural inclinations and avoid frustrating them are morally good” (49). When moral actions have good effects and nonintended bad effects that do not outweigh the good effects—as in cases of self-defense or the use of medicine and medical procedures—these complex actions retain their moral goodness, notwithstanding the bad effects. The reason for this is that the bad effects are not included in the agent’s intention. Lombardo presents the crucifixion of Christ as one of these complex cases in which the bad effects can be separated from the agent’s intention. Chapter 3 explores the reasoning associated with the principle of double effect to clarify how actions implicated in bad or evil effects can be judged to be morally good. Lombardo is hesitant to identify double effect as an isolated principle that is applicable within unique circumstantial cases. Rather, he presents double effect as “merely an algorithm for applying basic concepts to morally ambiguous actions” (72). For example, in addition to affirming that the intended effects of the action are consistent with our natural inclinations, in cases of double-effect reasoning “the action’s positive, intended effects [must] outweigh the action’s negative, nonintended effects” (73). This material, in turn, connects logically with the conclusion of chapter 4 on the ethics of self-sacrifice: “double effect reasoning shows that it can be acceptable, and even heroic, to cause our own death non-intentionally for the sake of some greater good” (79). The last chapter in part 1 applies these distinctions to the problem of God’s will and the moral evil involved in Christ’s crucifixion. Here, the basic dilemma that the book addresses is succinctly restated: “Being all good, God never wants... (shrink)

After a presentation of over ten different cases of suicide the author gives a brief review of the definitions of suicide found in the literature. Then he suggests a definition of his own: ‘A wo/man commits a suicide if s/he consciously initiates a sequence of events leading to her/his death.’ This definition does not entail any value statement about the act of suicide. We may agree that some acts of terminating one’s life deliberately command admiration as feats of heroism, (...) while others are deplorable as acts of cowardice. However, the principle of double effect does not permit to distinguish incontrovertibly a case of a suicidal death from a heroic death, says the author. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Guilt History:Benjamin's Sketch "Capitalism as Religion"Werner Hamacher (bio)Translated by Kirk Wetters (bio)History as Exchange EconomySince history cannot be conceived as a chain of events produced by mechanical causation, it must be thought of as a connection between occurrences that meets at least two conditions: first that it admit indeterminacy and thus freedom, and second that it nonetheless be demonstrable in determinate occurrences and in the distinct form of their (...) coherence. Relations can thus be called historical and can be recognized as historical only if they are determined by neither necessity nor chance, and if their causality is of a different order than the mechanical. The temporal structure of history can therefore be characterized on the one hand by the distinct connection of its elements—and on the other hand by the dissolution of all connections that do not assist these elements in achieving their independence.A temporal nexus that clearly does not satisfy these conflicting requirements has been characterized in one of the oldest texts of occidental philosophy as the time of guilt. According to the sentence of Anaximander (from about 500 BC), handed down by Simplicius in his commentary (530 AD) on Aristotle's Physics, the origin and end of all things is subordinated to the law of necessity (katà tó kreòn). "They must pay penance and be judged for their injustice, according to the order of time (katà tèn tou chrónou táxin)"—so the fragment reads in the translation offered by Nietzsche in his treatise "Philosophy in the Tragic Age of the Greeks." According to Anaximander, the sequence of time orders the rise and fall of all things and orders them in accordance with the law of guilt and punishment so that becoming (génesis) is a guilt (adikía) that must be expiated in perishing. Time and more precisely its táxis, the positing of time, is thought in Anaximander's sentence as an order of guilt and retribution, debt and payback. It is a time of economy in the sense that it is the time of law—and precisely a law that is valid for all beings, a táxis, a decree, an ordinance and an ordering—in which the unavoidable incurring of guilt is atoned in an equivalent penance that is just as unavoidable. The strict coherence of guilt and penance is ascertained by the principle of their equivalence. Time is therefore conceived here as a double process of coming into being and perishing, [End Page 81] a process that occurs in such a way that the genesis is erased in its passing away—so that time is thus erased by time itself.In Anaximander's sentence, however, time is not only the double-process of coming into being and passing away, it is—as a táxis—the common and constantly enduring medium of the exchange of the contrary but equivalent motions of coming into being and perishing. It is the time of the quid pro quo of everything that is generated and passes away within time. Its measure is a justice that represents itself as a táxis and thereby as the positing and the law of all becoming and vanishing, the law of physis and its demise as an onto-economic law. This taxiological order of time places every realm of the natural and human world under a law of substitution without exception; this also allows ethical, juridical, and economic concepts to substitute for one another within this order. The ethical dimension of justice, thus circumscribed by the order of time, is reduced to the juridical dimension of the decree, and both now define themselves according to the calculus of "an exchange economy in an eternally unchanging household of nature."1 It can only, however, be a matter of an ethics of time to the extent that this ethics, already juridified and economized, is subordinated to the schema of exchange, trade, and the equivalence of guilt and retribution. The time of history, ethical time, is thus interpreted in Anaximander's sentence as a normative time of inculpation and expiation. Whatever enters this táxis of time is thereby already guilty and can... (shrink)

The present essay explores plausible affinities between the Orphic theogony embedded in the Derveni papyrus and its interpretation in the mode of physikē philosophia by the Derveni author. It focuses specifically on the relationship between latent meaning and manifest content in the text as a whole. The Derveni author’s complex techniques of allegorical exegesis and his mental makeup are the subject-matter of the firstpart. The ways in which he is influenced by, and diverges from, Heraclitus in a crucial column of (...) the papyrus are taken as indicative of his specifically Orphic concerns. The sequence of the mythical events narrated in the poem is established in the following part, and those which seem to be original with the poet are distinguished from the traditional material of Hesiod’s Theogony. Special emphasis is put on the psychological significance that a narrative stressing a double or two-phased generation of the world-order, may have had for initiates of the so-called Orphic type. In the third part of the essay, a similar two-phased creation of the world-order is discerned in the Derveni author’s ‘scientific’or‘rational’cosmogony. A table of tentative correspondences between the Derveni author’s cosmogony and the Orphic poet’s theogony is also included. The final remarks explore the place of the Derveni author in ‘the ancient quarrel between philosophy and poetry’, and highlight what seems to have been his most perplexing concern: the simultaneous immanence and transcendence of divinity with respect to the world. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Denying the Body? Memory and the Dilemmas of History in DescartesTimothy J. ReissIn an essay first published in The New York Review of Books in January 1983, touching her apprenticeship as writer, the Barbadian /American novelist Paule Marshall described the long afternoon conversations with which her mother and friends used to relax in the family kitchen. She recalled how they saw things as composed of opposites; not torn, but (...) completed and made whole by them.Theirs was not a Manichean brand of dualism that sees matter, flesh, the body, as inherently evil, because they constantly addressed each other as “soully-gal”—soul: spirit; gal: the body, flesh, the visible self. And it was clear from their tone that they gave one as much weight and importance as the other. They had never heard of the mind/body split. 1This closing claim is surely less than self-evident. Whether or not the companions had heard of the mind/body split depends on the meaning given to the verb “hear.” Certainly it was embedded in their language, however much the phrase “soully-gal” might recombine its parts.Did the split come from Descartes and early European debates, linguistically colonizing all those who came within its sphere—Africans, Barbadians, Brooklynites? Did it come from a Christian heritage, with its haggling over bodily mortality and immortality of soul? Who knows? A first point is that it is still an everyday experience, deeply buried in language and so in the ideas, feelings, and meanings expressed in language. A second point is that the post-Cartesian debates—to simplify for a moment with an overly heavy [End Page 587] hand—were and are themselves but a variant within a much longer received wisdom. Nonetheless, such wisdom is now bound to that variant, which, willy-nilly, does give one set of parameters to a common experience—at least, to that of those of us who dwell under Western hegemonies. It gives them also, no doubt, to many who live within them at once less clearly and more contentiously.I would like to offer a further powerful instance here, simply to emphasize what and how much is at stake in the questions to be addressed. It occurs in a writing by the Guyanese novelist Wilson Harris, his Palace of the Peacock. First in a tetralogy, this novel recounts something like a journey away from a life of colonial and postcolonial violence and oppression towards a hoped-for rebirth in “fulfilment and understanding.” 2 Early on, the harsh protagonist, Donne, mocks the narrator, his mysterious “double” and “brother,” Dreamer, who has remarked their distance from “the folk.” “Is it a mystery of language and address?” asks Donne. Slightly bewildered, Dreamer struggles to suggest that the obstacle is less of language than of a deeper disjunction:“it’s an inapprehension of substance,” I blurted out, “an actual fear of the substance of life, fear of the substance of the folk, a cannibal blind fear in oneself. Put it how you like,” I cried, “it’s a fear of acknowledging the true substance of life. Yes, fear I tell you, the fear that breeds bitterness in our mouth, the haunting sense of fear that poisons us and hangs us and murders us. And somebody,” I declared, “must demonstrate the unity of being, and show...” I had grown violent and emphatic... “that fear is nothing but a dream and an appearance....” 3Recovery of unity might become a way to defeat political and historical violences. In the next novel in the sequence, one of two self-indulgently whining characters, accused of pining for a woman who has run away to seek education, explodes: “I don’t believe you can begin to see how some body like they born seeking for mind.” 4 For peoples of the colonized Americas, imbued with “the great civilization of the American Indian,” this urge, Harris then wrote in a critical essay, was simply the personal form of a social and political necessity to recover still-living elements of a culture for which “matter truly bore the imprint of genius,” refusing “the taboo of spirituality removed from sensuous direction.” 5 Recently, Harris has worried this... (shrink)