American Academy of Pediatrics (AAP) and American College of Medical Genetics (ACMG) recently provided two recommendations about predictive genetic testing of children. The Clinical Sequencing Exploratory Research Consortium's Pediatrics Working Group compared these recommendations, focusing on operational and ethical issues specific to decision making for children. Content analysis of the statements addresses two issues: (1) how these recommendations characterize and analyze locus of decision making, as well as the risks and benefits of testing, and (2) whether the guidelines conflict or (...) come to different but compatible conclusions because they consider different testing scenarios. These statements differ in ethically significant ways. AAP/ACMG analyzes risks and benefits using best interests of the child and recommends that, absent ameliorative interventions available during childhood, clinicians should generally decline to order testing. Parents authorize focused tests. ACMG analyzes risks and benefits using the interests of the child and other family members and recommends that sequencing results be examined for additional variants that can lead to ameliorative interventions, regardless of age, which laboratories should report to clinicians who should contextualize the results. Parents must accept additional analysis. The ethical arguments in these statements appear to be in tension with each other. (shrink)

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related (...) to local protein flexibility and disorder, large‐scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution. (shrink)

The aim of this paper is to highlight an interdependence between procedural and agential norms that undermines their neat separation when appraising argumentation. Drawing on the munāẓara tradition, we carve a space for sequencing in argumentation scholarship. Focusing on the antagonist’s sequencing of critical moves, we identify each sequence’s corresponding values of argumentation: coalescence, reliability, and efficacy. These values arise through the mediation of virtues and simultaneously underpin procedural as well as agential norms. Consequently, an ambiguity between procedure and (...) agent becomes apparent. This ambiguity hints at the potential for a virtue theory of argumentation that draws on procedural norms. (shrink)

Isn't probability 1 certainty? If the probability is objective, so is the certainty: whatever has chance 1 of occurring is certain to occur. Equivalently, whatever has chance 0 of occurring is certain not to occur. If the probability is subjective, so is the certainty: if you give credence 1 to an event, you are certain that it will occur. Equivalently, if you give credence 0 to an event, you are certain that it will not occur. And so on for other (...) kinds of probability, such as evidential probability. The formal analogue of this picture is the regularity constraint: a probability distribution over sets of possibilities is regular just in case it assigns probability 0 only to the null set, and therefore probability 1 only to the set of all possibilities. (shrink)

In cognitive neuroscience, dissociating the brain networks that ing—has thus become one of the best empirical situations subtend conscious and nonconscious memories constitutes a through which to study the mechanisms of implicit learning, very complex issue, both conceptually and methodologically.

ABSTRACT The apparent consistency of Sobel sequences famously motivated David Lewis to defend a variably strict conditional semantics for counterfactuals. If Sophie had gone to the parade, she would have seen Pedro. If Sophie had gone to the parade and had been stuck behind someone tall, she would not have seen Pedro. But if the order of the counterfactuals in a Sobel sequence is reversed—in the example, if is asserted prior to —the second counterfactual asserted no longer rings true. (...) This is the Heim sequence problem. That the order of assertion makes this difference is surprising on the variably strict account. Some argue that this is reason to reject the Lewis-Stalnaker semantics outright. Others argue that the problem motivates a contextualist rendering of counterfactuals. Still others maintain that the explanation for the phenomenon is merely pragmatic. I argue that none of these is right, and I defend a novel way to understand the phenomenon. My proposal avoids the problems faced by the alternative analyses and enjoys independent support. There is, however, a difficulty for my view: it entails that many ordinarily accepted counterfactuals are not true. I argue that this cost is acceptable. (shrink)

ABSTRACT There are two tenets about free agency that have proven difficult to combine: free agency is grounded in an agent’s possession or exercise of their reasons-responsiveness, only actual sequence features can ground free agency. This paper argues that and can only be reconciled if we recognise that their clash is just the particular manifestation of a wider conflict between two approaches to the notion of non-accidentality. According to modalism, p is non-accidentally connected to q iff p modally tracks (...) q. According to explanationism, p is non-accidentally connected to q iff q explains p in the right way. The conflict between these two approaches becomes manifest in Frankfurt-like cases for many notions, in which p and q are intuitively non-accidentally connected even though there is no modal tracking between them. Thus, and can’t be combined because the Frankfurt-cases upon which rests track explanationist intuitions, while the non-accidentality requirement of reasons-responsiveness in is usually spelled out in modalist terms. Hence, the possibility of an actual sequence reasons-responsiveness account depends on finding an explanationist approach to the non-accidentality requirement of reasons-responsiveness. (shrink)

Comparing the relative sensitivity of direct and indirect measures of learning is proposed as the best way to provide evidence for unconscious learning when both conceptual and operative definitions of awareness are lacking. This approach was first proposed by Reingold & Merikle (1988) in the context of subliminal perception. In this paper, we apply it to a choice reaction time task in which the material is generated based on a probabilistic finite-state grammar (Cleeremans, 1993). We show (1) that participants progressively (...) learn about the statistical structure of the stimulus material over training with the choice reaction time task, and (2) that they can use some of this knowledge to predict the location of the next stimulus in a subsequent “generation” task. However, detailed partial correlational analyses of the correspondence between performance during the reaction time task and the statistical structure of the training material showed that large effects remained even when controlling for explicit knowledge as assessed by the generation task. Hence we conclude (1) that at least some of the knowledge expressed through reaction time performance can not be characterized as conscious, and (2) that even when associations are found at a global level of analysis, dissociations can still be obtained when more detailed analyses are conducted. Finally, we also show that participants are limited in the depth of the contingencies they can learn about, and that these limitations are shared by the Simple Recurrent Network model of Cleeremans & McClelland (1991). (shrink)

According to L.E.J. Brouwer, there is room for non-definable real numbers within the intuitionistic ontology of mental constructions. That room is allegedly provided by freely proceeding choice sequences, i.e., sequences created by repeated free choices of elements by a creating subject in a potentially infinite process. Through an analysis of the constitution of choice sequences, this paper argues against Brouwer’s claim.

The article deals with the notion of the genetic code and its metaphorical understanding as a “language”. In the traditional view of the language metaphor of the genetic code, combinations of nucleotides are signs of amino acids. Similarly, words combined from letters represent certain meanings. The language metaphor of the genetic code, 171–200, 2011) assumes that the nucleotides stay in the analogy to letters, triples to words and genes to sentences. We propose an application of mathematical linguistic methods on the (...) notion of the genetic code. We provide quantitative analysis of mRNA strings and natural language texts. This analysis is sensitive to the detection of the code units hierarchy. We also take into consideration a representative quantitative analysis of DNA, RNA and proteins. Our analysis of mRNA confirms an assumption that the design of the genetic code cannot analogize DNA bases and letters. The notion of the letter is much more appropriate if analogized with triplets or amino acids, 187–191, 2017). (shrink)

Five recursively axiomatizable theories extending Kleene's intuitionistic theory FIM of numbers and numbertheoretic sequences are introduced and shown to be consistent, by a modified relative realizability interpretation which verifies that every sequence classically defined by a Π11 formula is unavoidable and that no sequence can fail to be classically Δ11. The analytical form of Markov's Principle fails under the interpretation. The notion of strongly inadmissible rule of inference is introduced, with examples.

One of the earliest applications of transfinite numbers is in the construction of derived sequences by Cantor [2]. In [6], the existence of derived sequences for countable closed sets is proved in ATR0. This existence theorem is an intermediate step in a proof that a statement concerning topological comparability is equivalent to ATR0. In actuality, the full strength of ATR0 is used in proving the existence theorem. To show this, we will derive a statement known to be equivalent to ATR0, (...) using only RCA0 and the assertion that every countable closed set has a derived sequence. We will use three of the subsystems of second order arithmetic defined by H. Friedman , which can be roughly characterized by the strength of their set comprehension axioms. RCA0 includes comprehension for Δmath image definable sets, ACA0 includes comprehension for arithmetical sets, and ATR0 appends to ACA0 a comprehension scheme for sets defined by transfinite recursion on arithmetical formulas. MSC: 03F35, 54B99. (shrink)

In this paper we describe a few interrelated issues for validating theories that posit levels of consciousness. First, validating levels of consciousness requires consensus about the ordering of conscious states, which cannot be easily achieved. This problem is particularly severe if we believe conscious states can be irreducibly smeared over time. Second, the relationship between conscious states is probably sometimes intransitive, which means levels of consciousness will not be amenable to a single continuous measure. Finally, even if a multidimensional approach (...) to levels of consciousness is adopted, we argue that there are further problems for its validation. (shrink)

Comparing the relative sensitivity of direct and indirect measures of learning is proposed as the best way to provide evidence for unconscious learning when both conceptual and operative definitions of awareness are lacking. This approach was first proposed by Reingold & Merikle (1988) in the context of subliminal perception. In this paper, we apply it to a choice reaction time task in which the material is generated based on a probabilistic finite-state grammar (Cleeremans, 1993). We show (1) that participants progressively (...) learn about the statistical structure of the stimulus material over training with the choice reaction time task, and (2) that they can use some of this knowledge to predict the location of the next stimulus in a subsequent “generation” task. However, detailed partial correlational analyses of the correspondence between performance during the reaction time task and the statistical structure of the training material showed that large effects remained even when controlling for explicit knowledge as assessed by the generation task. Hence we conclude (1) that at least some of the knowledge expressed through reaction time performance can not be characterized as conscious, and (2) that even when associations are found at a global level of analysis, dissociations can still be obtained when more detailed analyses are conducted. Finally, we also show that participants are limited in the depth of the contingencies they can learn about, and that these limitations are shared by the Simple Recurrent Network model of Cleeremans & McClelland (1991). (shrink)

We investigate maximal free sequences in the Boolean algebra \ {/}\text {fin}\), as defined by Monk :593–610, 2011). We provide some information on the general structure of these objects and we are particularly interested in the minimal cardinality of a free sequence, a cardinal characteristic of the continuum denoted \. Answering a question of Monk, we demonstrate the consistency of \. In fact, this consistency is demonstrated in the model of Shelah for \ :433–443, 1992). Our paper provides a (...) streamlined and mostly self contained presentation of this construction. (shrink)

For given Boolean algebras$\mathbb {A}$and$\mathbb {B}$we endow the space$\mathcal {H}(\mathbb {A},\mathbb {B})$of all Boolean homomorphisms from$\mathbb {A}$to$\mathbb {B}$with various topologies and study convergence properties of sequences in$\mathcal {H}(\mathbb {A},\mathbb {B})$. We are in particular interested in the situation when$\mathbb {B}$is a measure algebra as in this case we obtain a natural tool for studying topological convergence properties of sequences of ultrafilters on$\mathbb {A}$in random extensions of the set-theoretical universe. This appears to have strong connections with Dow and Fremlin’s result stating (...) that there are Efimov spaces in the random model. We also investigate relations between topologies on$\mathcal {H}(\mathbb {A},\mathbb {B})$for a Boolean algebra$\mathbb {B}$carrying a strictly positive measure and convergence properties of sequences of measures on$\mathbb {A}$. (shrink)

Fusion genes formed by chromosomal rearrangements are common drivers of cancer. Recent innovations in the field of next‐generation sequencing (NGS) have seen a dynamic shift from traditional fusion detection approaches, such as visual characterization by fluorescence, to more precise multiplexed methods. There are many different NGS‐based approaches to fusion gene detection and deciding on the most appropriate method can be difficult. Beyond the experimental approach, consideration needs to be given to factors such as the ease of implementation, processing time, associated (...) costs, and the level of expertise required for data analysis. Here, the different NGS‐based methods for fusion gene detection, the basic principles underlying the techniques, and the benefits and limitations of each approach are reviewed. This article concludes with a discussion of how NGS will impact fusion gene detection in a clinical context and from where the next innovations are evolving. (shrink)

The processing of fluent speech involves complex computational steps that begin with the segmentation of the continuous flow of speech sounds into syllables and words. One question that naturally arises pertains to the type of syllabic information that speech processes act upon. Here, we used functional magnetic resonance imaging to profile regions, using a combination of whole-brain and exploratory anatomical region-of-interest (ROI) approaches, that were sensitive to syllabic information during speech perception by parametrically manipulating syllabic complexity along two dimensions: (1) (...) individual syllable complexity, and (2) sequence complexity (supra-syllabic). We manipulated the complexity of the syllable by using the simplest syllable template—a consonant and vowel (CV)-and inserting an additional consonant to create a complex onset (CCV). The supra-syllabic complexity was manipulated by creating sequences composed of the same syllable repeated 6 times (e.g. /pa-pa-pa-pa-pa-pa/) and sequences of 3 different syllables each repeated twice (e.g. /pa-ta-ka-pa-ta-ka/). This parametrical design allowed us to identify brain regions sensitive to (1) syllabic complexity independent of supra-syllabic complexity, (2) supra-syllabic complexity independent of syllabic complexity and, (3) both syllabic and supra-syllabic complexity. High-resolution scans were acquired for 15 healthy adults. An exploratory anatomical ROI analysis of the supratemporal plane (STP) identified bilateral regions within the anterior two-third of the planum temporale, the primary auditory cortices as well as the anterior two-third of the superior temporal gyrus that showed different patterns of sensitivity to syllabic and supra-syllabic information. These findings demonstrate that during passive listening of syllable sequences, sublexical information is processed automatically, and sensitivity to syllabic and supra-syllabic information is localized almost exclusively within the STP. (shrink)

Implementing whole genome sequencing (WGS) in paediatric settings demands sensitive and nuanced examination. Critical reflection as to how and when to use this technology is particularly important. This commentary on Anderson et al's (2017) evaluation of the Genome Clinic study, which involved paediatric clinical WGS, provides an opportunity for such reflection. I scrutinise three issues raised in the study: (1) the non-separation of the choice over agreeing to diagnostic WGS and whether to receive adult-onset SVs; (2) the value of deliberation (...) regarding paediatric WGS and (3) the place of best interests in debates over returning adult-onset SVs. (shrink)

Collecting, comparing, and computing molecular sequences are among the most prevalent practices in contemporary biological research. They represent a specific way of producing knowledge. This paper explores the historical development of these practices, focusing on the work of Margaret O. Dayhoff, Richard V. Eck, and Robert S. Ledley, who produced the first computer-based collection of protein sequences, published in book format in 1965 as the Atlas of Protein Sequence and Structure. While these practices are generally associated with the rise (...) of molecular evolution in the 1960s, this paper shows that they grew out of research agendas from the previous decade, including the biochemical investigation of the relations between the structures and function of proteins and the theoretical attempt to decipher the genetic code. It also shows how computers became essential for the handling and analysis of sequence data. Finally, this paper reflects on the relationships between experimenting and collecting as two distinct “ways of knowing” that were essential for the transformation of the life sciences in the twentieth century. (shrink)

This paper studies the metric structure of the space Hr of absolutely summable sequences of real numbers with at most r nonzero terms. Hr is complete, and is located and nowhere dense in the space of all absolutely summable sequences. Totally bounded and compact subspaces of Hr are characterized, and large classes of located, totally bounded, compact, and locally compact subspaces are constructed. The methods used are constructive in the strict sense. MSC: 03F65, 54E50.

This paper sketches a way of supplementing classical mathematics with a motivation for a Brouwerian theory of free choice sequences. The idea is that time is unending, i.e. that one can never come to an end of it, but also indeterminate, so that in a branching time model only one branch represents the ‘actual’ one. The branching can be random or subject to various restrictions imposed by the creating subject. The fact that the underlying mathematics is classical makes such perhaps (...) delicate issues as the fan theorem no longer problematic. On this model, only intuitionistic logic applies to the Brouwerian free choice sequences, and there it applies not because of any skepticism about classical mathematics, but because there is no ‘end of time’ from the standpoint of which everything about the sequences can be decided. (shrink)

In order processing, consecutive sequences (e.g., 1‐2‐3) are generally processed faster than nonconsecutive sequences (e.g., 1‐3‐5) (also referred to as the reverse distance effect). A common explanation for this effect is that order processing operates via a memory‐based associative mechanism whereby consecutive sequences are processed faster because they are more familiar and thus more easily retrieved from memory. Conflicting with this proposal, however, is the finding that this effect is often absent. A possible explanation for these absences is that familiarity (...) may vary both within and across sequence types; therefore, not all consecutive sequences are necessarily more familiar than all nonconsecutive sequences. Accordingly, under this familiarity perspective, familiar sequences should always be processed faster than unfamiliar sequences, but consecutive sequences may not always be processed faster than nonconsecutive sequences. To test this hypothesis in an adult population, we used a comparative judgment approach to measure familiarity at the individual sequence level. Using this measure, we found that although not all participants showed a reverse distance effect, all participants displayed a familiarity effect. Notably, this familiarity effect appeared stronger than the reverse distance effect at both the group and individual level; thus, suggesting the reverse distance effect may be better conceptualized as a specific instance of a more general familiarity effect. (shrink)

Following our [6], though with somewhat different methods here, further variants of Goodstein sequences are introduced in terms of parameterized Ackermann–Péter functions. Each of the sequences is shown to terminate, and the proof-theoretic strengths of these facts are calibrated by means of ordinal assignments, yielding independence results for a range of theories: PRA, PA,$\Sigma ^1_1$-DC$_0$, ATR$_0$, up to ID$_1$. The key is the so-called “Hardy hierarchy” of proof-theoretic bounding finctions, providing a uniform method for associating Goodstein-type sequences with parameterized normal (...) form representations of positive integers. (shrink)

Transitional justice scholars are increasingly concerned with measuring the impact of transitional justice initiatives. Scholars often assume that TJ mechanisms must be properly designed and ordered to achieve lasting effect, but the impact of TJ timing and sequencing has attracted relatively little theoretical or empirical attention. Focusing on Latin America, this article explores variation within the region as to when TJ occurs and the order in which mechanisms are implemented. We utilize qualitative comparative analysis to assess the impact of TJ (...) timing and sequencing on democratic development. We find little evidence for path dependency owing to the chronological order of mechanisms. We do find, however, that amnesties and trials approach a sufficient condition for democratic consolidation in Latin America; trials, however, come closest to being a necessary condition for successful democratic consolidation. (shrink)

In a Common Law system, legal practitioners need frequent access to prior case documents that discuss relevant legal issues. Case documents are generally very lengthy, containing complex sentence structures, and reading them fully is a strenuous task even for legal practitioners. Having a concise overview of these documents can relieve legal practitioners from the task of reading the complete case statements. Legal catchphrases are (multi-word) phrases that provide a concise overview of the contents of a case document, and automated generation (...) of catchphrases is a challenging problem in legal analytics. In this paper, we propose a novel supervised neural sequence tagging model for the extraction of catchphrases from legal case documents. Specifically, we show that incorporating document-specific information along with a sequence tagging model can enhance the performance of catchphrase extraction. We perform experiments over a set of Indian Supreme Court case documents, for which the gold-standard catchphrases (annotated by legal practitioners) are obtained from a popular legal information system. The performance of our proposed method is compared with that of several existing supervised and unsupervised methods, and our proposed method is empirically shown to be superior to all baselines. (shrink)

In the late 1920s, the American obstetrician Joseph DeLee brought the motion-picture camera into the birth room. Following that era's trend of adapting industrial efficiency practices for medical environments, DeLee's films give spectacular and unexpected expression to the engineering concept of ‘streamlining’. Accomplishing what more tangible obstetric streamlining practices had failed to, DeLee's cameras, and his post-production manipulation, shifted birth from messy and dangerous to rationalized, efficient, death-defying. This was film as an active and effective medical tool. Years later, the (...) documentarian Pare Lorentz produced and wrote his own birth film,The Fight for Life(1940). The documentary subject of the film was DeLee himself, and the film was set in his hospitals, on the same maternity ‘sets’ that had once showcased film's remarkable streamlining capacity to give and keep life. Yet relatively little of DeLee was retained in the film's content, resulting in a showdown that, by way of contrast, further articulated DeLee's understanding of film's medical powers and, in so doing, hinted at a more dynamic moment in the history of medicine while speaking also to the process by which that understanding ceased to be historically legible. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci (...) in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)