We survey the use of club guessing and other PCF constructs in the context of showing that a given partially ordered class of objects does not have a largest, or a universal, element.

We show the relative consistency of ℵ1 satisfying a combinatorial property considered by David Fremlin (in the question DU from his list) in certain choiceless inner models. This is demonstrated by first proving the property is true for Ramsey cardinals. In contrast, we show that in ZFC, no cardinal of uncountable cofinality can satisfy a similar, stronger property. The questions considered by D. H. Fremlin are if families of finite subsets of ω1 satisfying a certain density condition necessarily contain all (...) finite subsets of an infinite subset of ω1, and specifically if this and a stronger property hold under MA + ¬CH. Towards this we show that if MA + ¬CH holds, then for every family ? of ℵ1 many infinite subsets of ω1, one can find a family ? of finite subsets of ω1 which is dense in Fremlins sense, and does not contain all finite subsets of any set in ?.We then pose some open problems related to the question. (shrink)

L’étude traite de différentes catégories de signatures (et/ou de noms d’auteurs) et de leur fonctionnement dans l’écriture de l’histoire. L’histoire est une écriture dialogique au sens où elle s’appuie sur les écrits d’autres spécialistes, mais aussi sur une matérialité documentaire signée par des acteurs de l’histoire. En se référant à la parole d’autrui, l’historien valide son propre travail. Le principal indice de ce dialogue est le nom propre d’auteur associé à un propos qui représente pour l’historien une référence. L’étude met (...) en évidence l’aptitude des noms d’auteur à recevoir une corporalité et/ou une voix. La thèse est la suivante: dès que le lecteur peut attribuer un corps et un certain renom à une signature, celle-ci peut être utilisée comme instrument de la preuve. Une attention particulière est portée aux signataires inconnus, aux noms des rédacteurs de «témoignages». Au centre de notre intérêt se trouvent les «ajouts» des historiens (titres, annotations, notes en bas de page, etc.) qui introduisent sur la scène académique les propos des «auteurs inconnus». Des ajouts accompagnant une carte postale, représentée dans l’ouvrage Lettres de Drancy, sont analysés de près. (shrink)

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences.

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and (...) be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non‐methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under‐appreciated. The action of SNORDs in non‐methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader‐Willi syndrome. (shrink)

In a recent paper, Cayirlioglu et al. report that the disruption of a specific miRNA, miR‐279, which normally acts to inhibit the transcription factor Nerfin‐1, uncovers a population of hybrid CO2 neurons in the Drosophila maxillary palp.1 Normally, fruit fly CO2 neurons are found only in the antennae, while mosquito CO2 neurons are found only in the maxillary palps. The hybrid neurons in this miRNA mutant may, thus, recapitulate an evolutionary intermediate unseen since the divergence of these two (...) dipteran lineages over 250 million years ago. BioEssays 30:621–623, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

If validated, diet‐derived foreign microRNA absorption and function in consuming vertebrates would drastically alter our understanding of nutrition and ecology. RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors. Therapeutic exploitation of RNAi in treating human disease is difficult because these accessory processes are absent or diminished in most animals. A recent report challenged multiple paradigms, suggesting that ingested microRNAs (miRNAs) are transferred to blood, accumulate in tissues, (...) and exert canonical regulation of endogenous transcripts. Independent replication of these findings has been elusive, and multiple disconfirmatory findings have been published. In the face of mounting negative results, any additional positive reports must provide the proverbial “extraordinary proof” to support such claims. In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract. (shrink)

While it has often been assumed that, in humans, synonymous mutations would have no effect on fitness, let alone cause disease, this position has been questioned over the last decade. There is now considerable evidence that such mutations can, for example, disrupt splicing and interfere with miRNA binding. Two recent publications suggest involvement of additional mechanisms: modification of protein abundance most probably mediated by alteration in mRNA stability1 and modification of protein structure and activity,2 probably mediated by induction of (...) translational pausing. These case histories put a further nail into the coffin of the assumption that synonymous mutations must be neutral. BioEssays 29:515–519, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Recent experimental evidence suggests that most of the genome is transcribed into non‐coding RNAs. The initial transcripts undergo further processing generating shorter, metabolically stable RNAs with diverse functions. Small nucleolar RNAs (snoRNAs) are non‐coding RNAs that modify rRNAs, tRNAs, and snRNAs that were considered stable. We review evidence that snoRNAs undergo further processing. High‐throughput sequencing and RNase protection experiments showed widespread expression of snoRNA fragments, known as snoRNA‐derived RNAs (sdRNAs). Some sdRNAs resemble miRNAs, these can associate with argonaute proteins and (...) influence translation. Other sdRNAs are longer, form complexes with hnRNPs and influence gene expression. C/D box snoRNA fragmentation patterns are conserved across multiple cell types, suggesting a processing event, rather than degradation. The loss of expression from genetic loci that generate canonical snoRNAs and processed snoRNAs results in diseases, such as Prader‐Willi Syndrome, indicating possible physiological roles for processed snoRNAs. We propose that processed snoRNAs acquire new roles in gene expression and represent a new class of regulatory RNAs distinct from canonical snoRNAs.Also watch the Video Abstract. (shrink)

The basic premise of the host‐defense theory is that genomic imprinting, the parent‐of‐origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral‐like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly‐repeated C/D‐box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as “genomic parasites”, contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. Such a view is supported (...) by evidence derived from studies of the imprinted snoRNA‐ and/or miRNA‐encoding Dlk1‐Dio3, Snurf‐Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between “foreign” and “endogenous” sequences is of crucial importance in the field of mammalian epigenetics. (shrink)

Science naively presupposes the intelligibility of the universe, necessary laws, and a universal truth. The author reflects on these presuppositions to arrive at a demonstration of God's existence. In a vigorous and exclamatory style, he condemns the alternative views of idealism, phenomenology, and philosophies of science which cannot rationally justify their faith in a universal truth. The only rational basis for these presuppositions is a theistic God--the "Vérité mesurante" and "Pensée fondatrice" of scientific reason.--A. B. D.

The recent discovery of microRNAs (miRNAs) in unicellular eukaryotes, including miRNAs known previously only from animals or plants, implies that miRNAs have a deep evolutionary history among eukaryotes. This contrasts with the prevailing view that miRNAs evolved convergently in animals and plants. We re‐evaluate the evidence and find that none of the 73 plant and animal miRNAs described from protists meet the required criteria for miRNA annotation and, by implication, animals and plants did not acquire any of their respective (...) miRNA genes from the crown ancestor of eukaryotes. Furthermore, of the 159 novel miRNAs previously identified among the seven species of unicellular protists examined, only 28 from the algae Ectocarpus and Chlamydomonas, meet the criteria for miRNA annotation. Therefore, at present only five groups of eukaryotes are known to possess miRNAs, indicating that miRNAs have evolved independently within eukaryotes through exaptation of their shared inherited RNAi machinery. (shrink)

In this article, we develop an approach for the moral assessment of research and development networks on the basis of the reflective equilibrium approach proposed by Rawls and Daniels. The reflective equilibrium approach aims at coherence between moral judgments, principles, and background theories. We use this approach because it takes seriously the moral judgments of the actors involved in R & D, whereas it also leaves room for critical reflection about these judgments. It is shown that two norms, namely reflective (...) learning and openness and inclusiveness, which are used in the literature on policy and technological networks, contribute to achieving a justified overlapping consensus. We apply the approach to a case study about the development of an innovative sewage treatment technology and show how in this case the two norms are or could be instrumental in achieving a justified overlapping consensus on relevant moral issues. (shrink)

Recently, transcriptome‐wide sequencing data have revealed the pervasiveness of intergenic long noncoding RNA (lncRNA) transcription. Subsets of lncRNAs have been demonstrated to crosstalk with and post‐transcriptionally regulate mRNAs in a microRNA (miRNA)‐dependent manner. Referred to as long noncoding competitive endogenous RNAs (lnceRNAs), these transcripts can contribute to diverse aspects of organismal and cellular biology, likely by providing a hitherto unrecognized layer of gene expression regulation. Here, we discuss the biological relevance of post‐transcriptional regulation by lnceRNAs, provide insights on recent (...) advances in the understanding of lnceRNA regulatory networks, and speculate on molecular factors that facilitate miRNA‐dependent crosstalk between lnceRNAs and other transcripts. (shrink)

Dentre todas as possibilidades de ação feminista, há a militância em espaço público e a prática em apoio às mulheres, bem como a levada de consciência sobre pautas feministas para as mulheres, tanto no âmbito privado como no público. Esta era a abordagem de Andrea Dworkin, que proferia discursos em marchas e levava suas próprias experiências para o âmbito da escrita, sua prática profissional. A mesma abordagem era utilizada por Suzanne Lacy, artista contemporânea que, através de instalações urbanas, realizava suas (...) ações de militância combinada à arte. Este trabalho visa traçar parâmetros comuns entre estas duas mulheres, focando em suas pautas e na reverberação de seus trabalhos um em relação ao outro, bem como na sociedade.Palavras-chave: Público. Arte Contemporânea. Feminismo. AbstractAmongst all possibilities of feminist action there’s the militant strategy: to take the word of action into the public space, to act in women’s aid, to talk to your target audience and bring your discourse to the people. That was Andrea Dworkin’s strategy, who would bring her speeches into women’s marches and take her experience into her writing, which was her profession. The same strategy was taken by Suzanne Lacy, contemporary artist who focuses on urban installations to mix political and artistic action. This paper correlates these two authors, focusing on their preferred subjects and how their works reverberated together and in society.Keywords: Public. Contemporary Art. Feminism. (shrink)

An appropriate kind of curved Hilbert space is developed in such a manner that it admits operators of $\mathcal{C}$ - and $\mathfrak{D}$ -differentiation, which are the analogues of the familiar covariant and D-differentiation available in a manifold. These tools are then employed to shed light on the space-time structure of Quantum Mechanics, from the points of view of the Feynman ‘path integral’ and of canonical quantisation. (The latter contains, as a special case, quantisation in arbitrary curvilinear coordinates when space is (...) flat.) The influence of curvature is emphasised throughout, with an illustration provided by the Aharonov-Bohm effect. (shrink)

The size and organization of the brain are determined by the activity of progenitor cells early in development. Key mechanisms regulating progenitor cell biology involve miRNAs. These small noncoding RNA molecules bind mRNAs with high specificity, controlling their abundance and expression. The role of miRNAs in brain development has been studied extensively, but their involvement at early stages remained unknown until recently. Here, recent findings showing the important role of miRNAs in the earliest phases of brain development are reviewed, and (...) it is discussed how loss of specific miRNAs leads to pathological conditions, particularly adult and pediatric brain tumors. Let‐7 miRNA downregulation and the initiation of embryonal tumors with multilayered rosettes (ETMR), a novel link recently discovered by the laboratory, are focused upon. Finally, it is discussed how miRNAs may be used for the diagnosis and therapeutic treatment of pediatric brain tumors, with the hope of improving the prognosis of these devastating diseases. (shrink)

This paper presents a new formal model for D–N explanation that gives intuitive criteria of acceptability, avoids the known trivializations, and links explanation with confirmation theory. Although set in the twenty-five year tradition of attempts to formalize D–N explanation, it proposes a new direction for the model that is to be distinguished from the syntactical and informational approaches by its introduction of restrictions which derive from the use which the D–N model can have in hypothesis testing. This model, illustrating the (...) verificational approach, revises the classic H–O requirements and amends the notion of partial self-explanation to meet a criticism to which the H–O notion is vulnerable. (shrink)

Complete works of Maṇḍanamiśra, Indian philosopher; includes study on his work also.

Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of “miRNA seed” dogma and the exploration of non‐canonical binding sites. Finally, it (...) makes comparisons between miRNA target prediction and transcription factor binding prediction, and questions the value of characterizing miRNA binding sites based on which miRNA nucleotides are paired with an mRNA. (shrink)

We investigate a possible form of Schrödinger’s equation as it appears to moving observers. It is shown that, in this framework, accelerated motion requires fictitious potentials to be added to the original equation. The gauge invariance of the formulation is established. The example of accelerated Euclidean transformations is treated explicitly, which contain Galilean transformations as special cases. The relationship between an acceleration and a gravitational field is found to be compatible with the picture of the ‘Einstein elevator’. The physical effects (...) of an acceleration are illustrated by the problem of the uniformly-accelerated harmonic oscillator. (shrink)