Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I (...) are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. (shrink)

A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag unigenes from 26 Triticeae cDNA libraries, were mapped to wheat homoeologous group 4 chromosomes using a set of deletion, ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the cumulative results of EST mapping in all homoeologous groups, as reported (...) elsewhere, that found the highest proportion of loci mapped to the B genome. Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous group 4 chromosomes, while 35% mapped to the short arms. The distal regions of chromosome arms showed higher numbers of loci than the proximal regions, with the exception of 4DL. This study confirmed the complex structure of chromosome 4A that contains two reciprocal translocations and two inversions, previously identified. An additional inversion in the centromeric region of 4A was revealed. A consensus map for homoeologous group 4 was developed from 119 ESTs unique to group 4. Forty-nine percent of these ESTs were found to be homoologous to sequences on rice chromosome 3, 12% had matches with sequences on other rice chromosomes, and 39% had no matches with rice sequences at all. Limited homology was found between wheat ESTs on homoeologous group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4 ESTs could be classified into functional categories on the basis of blastX searches against all protein databases. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice (...) of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)

Responding to recent concerns about the reliability of the published literature in psychology and other disciplines, we formed the X-Phi Replicability Project to estimate the reproducibility of experimental philosophy. Drawing on a representative sample of 40 x-phi studies published between 2003 and 2015, we enlisted 20 research teams across 8 countries to conduct a high-quality replication of each study in order to compare the results to the original published findings. We found that x-phi studies – as represented in our sample (...) – successfully replicated about 70% of the time. We discuss possible reasons for this relatively high replication rate in the field of experimental philosophy and offer suggestions for best research practices going forward. (shrink)

La traduction de l'epistrophe grecque en conversio latine a pu laisser entendre une continuite entre le retour des philosophies grecques neoplatoniciennes et l'evenement religieux proprement chretien de la conversion. Le paradigme en serait le passage de Plotin a Augustin. Mais peut-on oublier que les grecques classiques n'ont pas d'ethique du repentir et que, sans ce rapport au temps de la faute, la constitution de soi n'a ni le meme sens ni le meme lieu? C'est le travail du Centre A.J. Festugiere (...) de Paris X-Nanterre sur les entrecroisements et reprises entre philosophie et religion qui est a l'origine des etudes rassemblees en cet ouvrage. Que nous voyions apparaitre aujourd'hui une nouvelle forme de repentir publique convie a mieux distinguer deux modeles de constitution de soi qui se reconnaissent en ce que l'accent porte tantot sur l'etre et tantot sur le temps. (shrink)

Les colonies de Terre Sainte, en dépit de trois croisades successives, ont abordé le dernier quart du 13e siècle dans un état de faiblesse inquiétant. Le pape Grégoire X a essayé durant cinq ans de redresser la situation par tous les moyens. L'A. retrace tout d'abord la destinée exceptionnelle de ce pape, de son vrai nom Tebaldo Visconti, né à Plaisance en 1210 et mort à Arezzo en 1276. Il étudie ensuite l'action de Grégoire X dans son redressement spirituel de (...) l'Orient latin. Son désir profond de venir en aide à la Terre Sainte s'exprima aussi dans des mesures financières. Les limites de l'action du Saint-Siège sont étudiées ainsi que le soutien logistique des colonies franques de Syrie apporté au pape. L'évolution de la conjoncture internationale compromit sérieusement à partir de 1273 les retombées ses efforts. (shrink)

The quantified relevant logic RQ is given a new semantics in which a formula for all xA is true when there is some true proposition that implies all x-instantiations of A. Formulae are modelled as functions from variable-assignments to propositions, where a proposition is a set of worlds in a relevant model structure. A completeness proof is given for a basic quantificational system QR from which RQ is obtained by adding the axiom EC of 'extensional confinement': for all x(A V (...) B) -> (A V for all xB). with x not free in A. Validity of EC requires an additional model condition involving the boolean difference of propositions. A QR-model falsifying EC is constructed by forming the disjoint union of two natural arithmetical structures in which negation is interpreted by the minus operation. (shrink)

Let κ be a cardinal, and let H κ be the class of sets of hereditary cardinality less than κ ; let τ (κ) > κ be the height of the smallest transitive admissible set containing every element of {κ}∪H κ . We show that a ZFC-definable notion of long unfoldability, a generalisation of weak compactness, implies in the core model K, that the mouse order restricted to H κ is as long as τ. (It is known that some weak (...) large cardinal property is necessary for the latter to hold.) In other terms we delimit its strength as follows: Theorem Con(ZFC+ω2-Π 1 1-Determinacy) ⇒ ⇒Con(ZFC+V=K+∃ a long unfoldable cardinal ⇒ ⇒Con(ZFC+∀X(X # exists) + ‘‘ $\forall D \subseteq \omega_1 D$ is universally Baire ⇔ ∃r∈R(D∈L(r)))’’, and this is set-generically absolute). We isolate a notion of ω-closed cardinal which is weaker than an ω1-Erd\ os cardinal, and show that this bounds the first long unfoldable: Theorem Let κ be ω -closed. Then there is a long unfoldable ł<κ. (shrink)

Рассматриваются актуальные проблемы философской антропологии, проводится анализ парадоксов и противоречий, возникающих при изучении человека, тех кардинальных сдвигов в культуре, которые открыли новые стороны человеческого бытия. Для студентов.