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)

İndividualizm və xüsusilə personalizm filosof-mütəfəkkirlərin diqqətini xüsusilə cəlb edən məsələlər sırasında olublar. İnsanın cəmiyyət ilə münasibətlərində öz xüsusiyyətləri, özgürlüyü və təkrar olunmazlığını qoruyub saxlamasını ifadə edən bu problemi müəyyən etməyin əhəmiyyətindən danışsaq, konkret bir şəxsə məxsus göstəricilərdən çıxış etməklə bütöv və hərtərəfli nəticə əldə etmək mümkündür. Qeyd olunan vəzifəni həyata keçirmək o qədər də asan deyildir. Çünki söhbət müəyyən bir şəxsi başqalarından ayırmaqdan başlayaraq, onun unikallığının formalaşması və mövcudluğunun müəyyən olunmasına qədər davam edən bir prosesi öyrənməkdən gedir. Dünyaya fərd kimi (...) gələn insan öz fəaliyyəti, özünüdərketməsi sayəsində şəxsiyyətin qabil ola biləcəyi bir varlığa çevrilə bilər. Məhz cəmiyyətin normal fəaliyyəti və inkişafı üçün onun hər bir üzvünün müəyyən qədər özünəməxsusluğu zəruridir. Və cəmiyyət üzvlərinin rəngarəngliyi, burada aydın ifadə olunmuş fərdiyyətlər, şəxsiyyətlərin mövcudluğu hər bir ictimai quruluşun, onun mədəniyyətinin həqiqi zənginliyini təmin edir. Buna görə də, insanların fərdi özünəməxsusluğuna malik olması sosial inkişafın qanunauyğunluğu kimi də qəbul edilir. Məqalədə Avropa personalistlərinin fikirlərinə istinadən belə proseslər izlənilib. (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)

The second half of the 1940s left its mark on the history of Soviet scholarship [nauka] as a special period in the interrelations between scholarship and society, as a time of direct encroachment on the development of scholarship by the totalitarian state. This direct ideological diktat over the activity of scholars [uchenye] took the form of scholarly [nauchnye] discussions, as they were called. They were an expression of the striving of Party-bureaucratic structures to unify the development of knowledge and to (...) impose like-mindedness on the basic directions of scholarly activity. References to the philosophical discussion, the Lysenko session of the Lenin All-Union Academy of Agriculture [VASKhNIL], the intrusion into the development of physics and chemistry, the discussions on issues of linguistics, physiology, etc., have become commonplace and have entered the textbooks, although the extent to which they have been studied varies. (shrink)

In the article the problem of transformation of the information received by the user on the Internet into his knowledge is investigated. The paper uses the main special scientific and logical research methods used in the social and humanitarian sciences. At the same time, the methods of systematic and value-worldview analysis of the phenomena of the spiritual world of a person are distinguished by the degree of significance, which allow us to study the problem of the dialectic of knowledge and (...) information on the Internet not in isolation, but in connection with the main phenomena of the spiritual life of people, taking into account the priority of value-worldview structures. The goal of the work is to find a priority factor that provides a higher degree of accuracy in the transformation of information from the Internet into human knowledge. It is shown that the nature of the world wide web to a certain extent complicates the process of translating information coming to a person into his knowledge. It is concluded that the condition for the transformation of information received by the user on the Internet is the cognitive activity of a person, due primarily to the development of its value and ideological sphere. If the cognizing person has sufficiently developed and stable value – ideological foundations of personality, he successfully realizes himself as a developing subject, an active participant in knowledge. On the contrary, insufficiently stable value-worldview sphere can lead to passive perception of information by the individual, adaptation to reality, simplification of personality. Information from the Internet in the most adequate form is transformed into a person’s knowledge on the basis of his own cognitive activity, in the presence of intellectual and volitional capabilities for verifying the information available on the Network. (shrink)

Law is indispensable to the public's health. The twentieth century proved this true as law contributed to each of the century's ten great public health achievements: vaccination, healthier mothers and babies, family planning, safer and healthier foods, fluoridation of drinking water, the control of infectious diseases, the decline in death from heart disease and stroke, recognition of tobacco use as a health hazard, motor vehicle safety, and safer workplaces.The readers of this journal can give examples of the relevant types of (...) laws with ease: Jacobson v. Massachusetts, the 1905 U.S. Supreme Court case that upheld the constitutionality of compulsory vaccination; mandatory immunization for school admission; authorization of state prenatal care programs; mandatory fortification of foods; Title X of the Public Health Service Act; the Pure Food and Drugs Act of 1906; the Safe Drinking Water Act of 1974, and hundreds of state and local enactments regulating food; fluoridation ordinanceswater, and sanitation; the Surgeon General's warning notices on cigarette packs and restrictions on marketing tobacco; seat belt laws and mandated vehicle and highway design features; and laws like the federal Occupational Safety and Health Act of 1970 that regulate working conditions. (shrink)

Law is indispensable to the public's health. The twentieth century proved this true as law contributed to each of the century's ten great public health achievements: vaccination, healthier mothers and babies, family planning, safer and healthier foods, fluoridation of drinking water, the control of infectious diseases, the decline in death from heart disease and stroke, recognition of tobacco use as a health hazard, motor vehicle safety, and safer workplaces.The readers of this journal can give examples of the relevant types of (...) laws with ease: Jacobson v. Massachusetts, the 1905 U.S. Supreme Court case that upheld the constitutionality of compulsory vaccination; mandatory immunization for school admission; authorization of state prenatal care programs; mandatory fortification of foods; Title X of the Public Health Service Act; the Pure Food and Drugs Act of 1906; the Safe Drinking Water Act of 1974, and hundreds of state and local enactments regulating food; fluoridation ordinanceswater, and sanitation; the Surgeon General's warning notices on cigarette packs and restrictions on marketing tobacco; seat belt laws and mandated vehicle and highway design features; and laws like the federal Occupational Safety and Health Act of 1970 that regulate working conditions. (shrink)

The recent revival of scholarly interest in Suetonius provides a good occasion to emend a long-standing crux in Joannes Lydus' description of Suetonius' dedication of his Vitae Caesarum to his friend the praetorian prefect Septicius Clarus. The codex unicus Caseolinus has Τράγκυλλος τοίνυν τος τν Καισάων βίους ν γράμμασιν † ποτίνων † Σεπτικί, ς ν παρχος τν πραιτωριανν σπειρν πì ατο. The conjectures ποτείνων by J. D. Fuss and ποτείνων by I. Bekker do little to improve the sense, and although (...) W. Kroll's προτείνων gives the meaning required by the context , προ- would not easily have been misread as πο-. For ποτίνων read νατείνων. For parallels compare BGU ii , 613.3–4 'Ανέτινα βιβλ[ίδι]α τλαμπροτάτ [γεμόνι] in a papyrus from the reign of Antoninus Pius cited by LSJ, and several other passages, most of which I owe to the supplement to Preisigke and Kiessling's Wörterbuch der griechischen Papyrusurkunden and to Dr Francisco R. Adrados of the Diccionario Griego-Español: Sammelbuch x , 10527.5–7 ['Ανέτε]ινά σοι, κ[ύριε,]…ναφόρ[ιον… of a.d. 152–3, P. Fouad iii , 26.5–10 , 8252.5–10) Ο νέτινάσυ τ κυρί βιβλιδίου…ντίγραφον πέταξα of a.d. 157–9, P. Oslo. iii , 80.21 ο νέτιναν βιβλιδί[ου…written sometime after March 7, a.d. 161, Sammelbuch iv 7472.3 'Ανέτεινά [σοι, κύριε πίτροπε, βιβλείδιον of a.d. 164, Sammelbuch vi.3 9339.24–7 13.5–7) ο νετείναμεν τ [κρατίσ τρχιερε O]λπί Σερηνιαν βιβλιδίου…[…] ντίγραφον πετάξαμεν from a.d. 178 or a little later, P. Mich. xii 616.13–14 τ δίκαιά μου βιβλειδί νγράψασ νέτεινα Νεμεσιαν πωσ τα[]τα διαπέμψηται[τ ]πιτρόπ from ca. a.d. 182, P. Cornell 14.2–4 ο νέτει[να τ κρατίστ πιστρ]ατηγ Κλαυδί [Ξενοφντι βιβλδίο]υ from a.d. 180–92, Wilcken, Chrestomathie 461.3–5 О[ νέ]τεινα τ λαμπροτάτ [γεμόνΚ]υίντω[ι] Μαικίωι λαιτίωι βιβλιδίου…ντίγραφον [ποτάξασ] from the beginning of the third century, and Sammelbuch v , 8246.3–4 α συνηγερούμεναι λιβέλλον νέτιναν π τν παρχον ξουσίαν from a.d. 340. (shrink)

The recent revival of scholarly interest in Suetonius provides a good occasion to emend a long-standing crux in Joannes Lydus' description of Suetonius' dedication of his Vitae Caesarum to his friend the praetorian prefect Septicius Clarus. The codex unicus Caseolinus has Τράγκυλλος τοίνυν τος τν Καισάων βίους ν γράμμασιν † ποτίνων † Σεπτικί, ς ν παρχος τν πραιτωριανν σπειρν πì ατο. The conjectures ποτείνων by J. D. Fuss and ποτείνων by I. Bekker do little to improve the sense, and although (...) W. Kroll's προτείνων gives the meaning required by the context, προ- would not easily have been misread as πο-. For ποτίνων read νατείνων. For parallels compare BGU ii, 613.3–4 'Ανέτινα βιβλ[ίδι]α τλαμπροτάτ [γεμόνι] in a papyrus from the reign of Antoninus Pius cited by LSJ, and several other passages, most of which I owe to the supplement to Preisigke and Kiessling's Wörterbuch der griechischen Papyrusurkunden and to Dr Francisco R. Adrados of the Diccionario Griego-Español: Sammelbuch x, 10527.5–7 ['Ανέτε]ινά σοι, κ[ύριε,]…ναφόρ[ιον… of a.d. 152–3, P. Fouad iii, 26.5–10, 8252.5–10) Ο νέτινάσυ τ κυρί βιβλιδίου…ντίγραφον πέταξα of a.d. 157–9, P. Oslo. iii, 80.21 ο νέτιναν βιβλιδί[ου…written sometime after March 7, a.d. 161, Sammelbuch iv 7472.3 'Ανέτεινά [σοι, κύριε πίτροπε, βιβλείδιον of a.d. 164, Sammelbuch vi.3 9339.24–7 13.5–7) ο νετείναμεν τ [κρατίσ τρχιερε O]λπί Σερηνιαν βιβλιδίου…[…] ντίγραφον πετάξαμεν from a.d. 178 or a little later, P. Mich. xii 616.13–14 τ δίκαιά μου βιβλειδί νγράψασ νέτεινα Νεμεσιαν πωσ τα[]τα διαπέμψηται[τ ]πιτρόπ from ca. a.d. 182, P. Cornell 14.2–4 ο νέτει[να τ κρατίστ πιστρ]ατηγ Κλαυδί [Ξενοφντι βιβλδίο]υ from a.d. 180–92, Wilcken, Chrestomathie 461.3–5 О[ νέ]τεινα τ λαμπροτάτ [γεμόνΚ]υίντω[ι] Μαικίωι λαιτίωι βιβλιδίου…ντίγραφον [ποτάξασ] from the beginning of the third century, and Sammelbuch v, 8246.3–4 α συνηγερούμεναι λιβέλλον νέτιναν π τν παρχον ξουσίαν from a.d. 340. (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.