Until recently, retention of introns in mature mRNAs has been regarded as a consequence of mis‐splicing. Intron‐retaining transcripts are thought to be non‐functional because they are readily degraded by nonsense‐mediated decay. However, recent advances in next‐generation sequencing technologies have enabled the detection of numerous transcripts that retain introns. As we review herein, intron‐retaining mRNAs play an essential conserved role in normal physiology and an emergent role in diverse diseases. Intron retention should no longer be overlooked as a key mechanism that (...) independently reduces gene expression in normal biology. Exploring its contribution to the development and/or maintenance of diseases is of increasing importance. (shrink)

Preparing the Next Generation of Oral Historians is an invaluable resource to educators seeking to bring history alive for students at all levels. Filled with insightful reflections on teaching oral history, it offers practical suggestions for educators seeking to create curricula, engage students, gather community support, and meet educational standards. By the close of the book, readers will be able to successfully incorporate oral history projects in their own classrooms.

Résumé : Le PPBS a été conçu comme un instrument destiné à ceux qui décident de l'allocation des ressources publiques : il doit leur permettre de prendre de meilleures décisions. S'il est très difficile de repérer et de juger les choix que le développement du système a inspirés aux Etats-Unis, il n'en est pas mains certain que ses résultats tangibles sant maigres car la masse des anciens programmes, principale source potentielle de moyens nouveaux, n'a guère été remise en question.La valeur (...) intrinsèque du PPBS ne peut être mise en cause. Ce qui doit l'être, c'est la lenteur de son développement, qui demeure peu avancé. Cette lenteur s'explique, car le système ne peut produire des fruits dans une terre stérile qu'on n'a pas préparée.La brutalité et les maladresses de l'opération déclenchée en 1965 dans le gouvernement fédéral américain ne pouvaient que renforcer la résistance au changement et retarder, sinon compromettre, le succès final. Les perspectives demeurent heureusement favorables, puisque la nouvelle administration ne semble pas décidée à faire machine arrière et que les Etats et Villes ont démarré sous de bien meilleurs auspices.La principale conclusion qu'imposent les expériences américaines est que toute juridiction intéressée par le PPBS doit impérativement développer, de la façon la plus générale, la volonté d'instaurer le système et s'assurer les moyens de le faire. C'est dire qu'il est peu sage d'engager la bataille sur tous les fronts à la fois : il faut tenter des percées. Mais c'est dire aussi combi en l'information et la formation sant essentielles. A cet égard, l'installation généralisée de certains éléments du système, à savoir la structure de programmes et le budget-programme, loin de présenter des inconvénients, peut constituer un excellent exercice en dehors de son utilité directe pour le preneur de décision. La bataille en cause est surtout celle de la conviction: l'outil est prêt, il est bon, encore faut-il que l' ouvrier accepte de s'en servir.Samenvatting:Planning-programming-budgeting werd ontworpen als een instrument voor diegenen die beslissen over de toewijzing van de overheidsmiddelen.Dit instrument moet de beslissers in staat stellen betere beslissingen te treffen. Het is niet makkelijk deze beslissingen op te sporen en te beoordelen welke in de Verenigde Staten getroffen werden onder invloed van de ontwikkeling van deze systeembenadering. Toch is het met vrij grote zekerheid te stellen dat de tastbare resultaten gering zijn omdat de veelheid aan oude programma's die tenslotte toch de voornaamste potentiële bronnen zijn van nieuwe middelen, nooit werden aangevochten.De intrinsieke waarde van PPBS kan daarom evenwel niet worden genegeerd. Wat wel dient aangeklaagd is de traagheid van zijn aanslepende ontwikkeling. Deze traagheid is te verklaren door het feit dat het systeem slechts vruchten kan afwerpen zo het ingeplant wordt in degelijk voorbereid terrein.De brutaliteit en de onhandigheden bij de operatie die in 1965 werd ingezet in het amerikaans federaal overheidsbestel konden niets anders dan de weerstand tegen de verandering versterken en afbreuk doen aan het uiteindelijk slagen van het systeem. Gelukkiglijk blijven de vooruitzichten gunstig want de nieuwe beleidsvoerders sinds de presidentsverkiezingen, blijken ermee te willen doorgaan en de staten en lokale overheden zijn ermee van wal gestoken onder veel betere omstandigheden. Het doorslaggevend besluit uit de amerikaanse ervaringen terzake is wel dat elke instantie welke belangstelling heeft voor PPBS, nodig moet op zo breed mogelijk vlak de wil doen groeien om het systeem te ontwikkelen en er ook de nodige middelen toe ter beschikking stellen. Dit betekent tevens dat het weinig aan te bevelen is de strijd op alle fronten terzelvertijd aan te binden maar wel geleidelijk doorbraken te verwezenlijken. Dit brengt dan evenwel ook met zich dat informatie en vorming essentieel zijn bij deze strategie. In dit verband moet dan ook gezegd worden dat reeds het invoeren van sommige deelementen van het systeem, zoals de programmastructuur en het programmabudget, voor de beslisser nuttig kan zijn voor zijn persoonlijk inzicht en vorming.De te voeren actie dient nog slechts te worden toegespitst op het overtuigen van de verantwoordelijken. Het instrument is immers gebruiksklaar en degelijk, er is alleen nog het wachten op de wil van de gebruiker dit instrument ter hand te nemen. (shrink)

Oxford Scholarly Classics is a new series that makes available again great academic works from the archives of Oxford University Press. Reissued in uniform series design, the reissues will enable libraries, scholars, and students to gain fresh access to some of the finest scholarship of the last century.

Mishel Fuco not only influenced the consciousness of modern West, but changed the modus of thinking, the way of perception of many traditional notions, transformed the opinions about the reality, history, person. Philosopher’s principle research programme which attaches the entirety to his works is “archeology of knowledge” programme, the search of human knowledge’s original layers. Let us mark that all Fuco’s works in 1960s are devoted to main aim: to clear up the conditions of historical origin of different mental aims (...) and social institutions in the culture of the Modern Time. Though in the whole this common aim remained for Fuco invariable, but the level on which he realizes his research search is changing constantly and rather logically. Relations of power, and to be more exact,accumulations of power and knowledge, social and cognitive which define all the aggregate of specific possibilities of culture in each given historical period. More than that the philosopher offers the particular prospects of sight of modern society and precisely totality of power relations, its ubiquitous nature and specific productivity which produces itself in each moment in any point or rather in any attitude from one point to another. From Fuco’s point of view the power is everywhere and not because it involves everything but because it comes from everywhere. The power is productive in that degree in which it is not associated with one definite imperious instance but pierces all kinds of activity in society, putting on its indelible stamp, developing under definite angle and due to this factit causes products, produced by them. The power induces and at the same time determines the fact which appears as a result of its inducement. The thirst of supremacy, which surrounds the individual and is focused on it as on the center of its use of force, comes out as a defining sign. It should be noticed that Fuco’s conception of power is not reduced to the understanding it as anonymous impersonal net of relations, piercing all society. It is supplemented by power treatment,coming out in “designed” look of definite imperious structure or imperious institute. (shrink)

City archives, mined by Aristotle for his Didaskaliai, preserved a reasonably complete record of dramatic productions in the fifth century. But how far back did these archives go? The so-called Fasti, an inscription set up c. 346 and listing dithyrambic, comic and tragic victors year by year, must have been based on the same archives, but went back, it is thought, only as far as 502/1. Its heading πρ]τον κμοι ἦσαν τ[ι διονσ]ωι τραγωιδο δ[, however supplemented, implies an intention of (...) going back to the beginning of things, in other words to the beginning of the archival record. This raises serious doubt as to whether that record went back to the alleged date of Thespis' première, or indeed to those given for Choerilus' and Phrynichus'. (shrink)

A Papyrus commentary on Alcman published in 19571 brings us news of a poem in which Alcman “physiologized”. The lemmata and commentary together witness to a semi-philosophical cosmogony unlike any other hitherto known from Greece. The evidence is meagre, but it seems worth while to see what can be made of it; for it is perhaps possible to go a little farther than has so far been done.

A weak form of intuitionistic set theory WST lacking the axiom of extensionality is introduced. While WST is too weak to support the derivation of the law of excluded middle from the axiom of choice, we show that beefing up WST with moderate extensionality principles or quotient sets enables the derivation to go through.

In its American context the case of baby Messenger, a preterm infant disconnected from life-support by his father and allowed to die has generated debate about neonatal treatment protocols. Limited by the legal and ethical norms of the United States, this case did not consider treatment protocols that might be available in other countries such as Denmark and Israel: threshold protocols whereby certain classes of newborns are not treated, and preemptive abortion allowing one to choose late-term abortion rather than risk (...) delivery. Each offers a viable and ethically sound avenue for dealing with the economic and social expense of anomalous newborns by aborting or not treating those most likely to burden the health care system. Objections that these protocols are antithetical to American bioethical principles are considered but rejected as each policy answers to economic justice, utility and respect for autonomy. (shrink)

Adenosine transport in cultured human umbilical vein endothelial cells (HUVEC) was characterized and shown to be mediated by a single facilitated diffusion mechanism. Initial rates of adenosine influx at 22 degrees C were saturable [apparent Michaelis constant, 69 +/- 10 mu M; maximum velocity (V-max), 600 +/- 70 pmol.10(6) cells(-1).s(-1)] and inhibited by nitrobenzylthioinosine (NBMPR). Formycin B had an unusually high affinity [inhibitory constant K-i), 18 +/- 4.3 mu M], whereas inosine had a low affinity (K-i, 440 +/- 68 mu (...) M) and nucleobases were without effect on adenosine influx. The number of transporters (1.2 x 10(6) sites/cell) was estimated by NBMPR equilibrium binding (apparent dissociation constant, 0.11 +/- 0.01 nM; maximum binding, 2.0 +/- 0.15 pmol/10(6) cells). In addition, we compared these endothelial cells with those obtained from cords from pregnancies complicated by diabetes (HUVEC-D), since embriopathy may occur in these conditions. HUVEC-D exhibited a 2.3-fold reduction in both the V-max for adenosine influx and the maximum number of NBMPR binding sites (260 +/- 40 pmol.10(6) cells(-1).s(-1) and 0.86 +/- 0.08 pmol/10(6) cells, respectively). However, the turnover number for each nucleoside transporter in normal and diabetic HUVEC was similar (approximate to 300 adenosine molecules/s). Adenosine metabolism at 10 mu M in HUVEC-D was modified compared with normal cells. Intracellular phosphorylation (> 90%) was the predominant pathway in normal HUVEC, whereas in HUVEC-D, substantial levels of adenine and adenosine were detected. The present results demonstrate therefore the downregulation of the NBMPR-sensitive nucleoside transporter and changes in adenosine metabolism in HUVEC from diabetic pregnancies. (shrink)