Mixed lineage leukemia (MLL) fusion protein (FP)‐induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild‐type (WT) MLL, MLL‐FPs, and other partners such as the chromatin‐associated protein LEDGF and the transcription factor C‐Myb to promote leukemogenesis. The newly solved co‐crystal structure illustrating the menin–MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL‐FPs (...) to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL‐FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain‐containing Brd4‐related pathways to sustain MLL‐FP‐induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL‐FP leukemias. (shrink)

Although the advising literature has emphasized the importance of good academic advising, there has been little emphasis on ethical issues. NACADA: The Global Community for Academic Advising provides Core Values to guide ethical behavior. This study used an experimental design to examine perspectives of ethical behavior among faculty, staff, and students. All groups could differentiate between ethical and unethical extremes, but students had difficulty differentiating between ethical and neutral behavior. All groups hesitated to rate advisors as highly ethical or unethical. (...) Even when behavior was seen as less ethical, students and faculty/staff perceived limited opportunity for students to do something about that behavior, such as change advisors. Suggestions are offered to increase the likelihood of more ethical behavior within advisement. (shrink)

The Planteome project provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology, and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides (...) access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. (shrink)

In den letzten drei Dekaden ist es zu einer Renaissance des Republikanismus gekommen. Ein spezifisch republikanisches Freiheitsverstandnis und die Debatte um entpolitisierende Wirkungen komplexer liberaler Demokratien haben sich dabei als in hohem Masse anschlussfahig an eine Vielzahl gegenwartiger Diskurse - von Global Governance bis hin zu Postdemokratie - erwiesen. Das Verstandnis von Republikanismus als einer modernen politischen Theorie wurde so weiter gestarkt und republikanische Ansatze gelten wieder als der zentrale Gegenspieler eines liberalen Staats- und Politikverstandnisses. Der Sammelband greift diese Renaissance (...) auf und bietet einen fur den deutschen Sprachraum bis dato fehlenden Uberblick uber Entwicklungstendenzen und Debatten im modernen republikanischen Denken. Er liefert eine Systematisierung von Ansatzen und Stromungen und erortert die Leistungsfahigkeit republikanischer Theorie gerade mit Blick auf Gegenwartsfragen. Mit Beitragen von: Richard Bellamy, Dorothea Gadeke, Philip Holzing, Sebastian Huhnholz, Marcus Llanque, Horst Mewes, Andreas Oldenbourg, Emanuel Richter, Daniel Schulz, Winfried Thaa, Thorsten Thiel, Christian Volk, Florian Weber und Sabrina Zucca-Soest. (shrink)

Cooper, Austin Some years ago a priest who was dying told me that he had not had a spiritual director for years: he just kept reading St Teresa. Having a continuing conversation with a holy person by engaging with his or her writings would seem to conform to our beliefs: in the Apostles' Creed we affirm that the Holy Spirit enlivens the church and the communion of saints. And T. S. Eliot articulated the truth in poetic terms when he (...) wrote, 'the communication of the dead is tongued with fire beyond the language of the living'. (shrink)

Die politische Ideengeschichte kennt nicht viele Autoren, die derart umstritten sind, wie der Abbé Sieyés: Für manche Interpreten ist er Wegbereiter des Jakobiner-Terrors, für andere dagegen der Vater des parlamentarischen Regierungssystems unserer Zeit. Der vorliegende Band unterzieht diese und ähnliche Klischees einer kritischen Prüfung.

The Oxford or Tractarian Movement and later Ritualists and Anglo-Catholics schooled numerous converts in elements of the Catholic faith. Foremost among them was John Henry Cardinal Newman, one of the original founders of the Oxford Movement. Converts numbered in the hundreds and included another cardinal, Henry Edward Manning, the second Archbishop of Westminster, the religious foundress Cornelia Connelly, the priest novelist Robert Hugh Benson and later literary figures such as G.K. Chesterton, Evelyn Waugh and Mgr Ronald Knox. American historian, Patrick (...) Allitt, has argued that on both sides of the Atlantic converts dominated Catholic intellectual life between 1840 and 1960. While such 'Tractarian' converts have indeed greatly influenced Catholic life, many 'Tractarians' who never converted have also had a considerable impact on English-speaking Catholicism. C.S. Lewis is an obvious example. But there have been others, including author Charles Williams, poet T.S. Eliot and theologians John Macquarrie and Michael Ramsey. The author Dorothy L. Sayers also deserves to be counted among their number. (shrink)

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and C4, (...) which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level. (shrink)

In What is Philosophy?, Deleuze and Guattari make the claim that ‘[i]t may be that believing in this world, in this life, becomes our most difficult task, or the task of a mode of existence still to be discovered on our plane of immanence today. This is the empiricist conversion.’ What are we to make of such a calling? The paper explicates why and in what sense this statement is of exemplary significance both for an appropriate understanding of Deleuze's political (...) thought and for a most timely conceptualisation of politics in a world so clearly defined by immanence, and nothing but immanence. I argue that Deleuze's rigorously constructive approach to the world is not beyond politics, as some recent readings have declared (e.g. those of Badiou and Hallward). Rather, we have to appreciate that in Deleuze and Guattari's demand for a ‘belief in this world’ the political intersects with the dimension of the ethical in such a way that our understanding of both is transformed. Only after this ‘empiricist conversion’ can we truly think of a Deleuzian politics that does justice to a plane of immanence ‘immanent only to itself’. (shrink)

Conversing happily with my son we had been driving home when my mobile phone rang. Startled at the sound of my obstetrician's voice I had pulled off to the side of the road. At 18 weeks gestation I was told in a factual tone that the results from my serum screen had come back, indicating that our baby was at increased risk of Trisomy 18. Gripping the steering wheel my head had spun as he talked, explaining that Trisomy 18 was (...) worse than Trisomy 21 because our baby was not going to live. We had been thrilled when we heard the news of my pregnancy but now my temples throbbed and tears brimmed in my eyes. Suddenly my world was turned upside down and it had felt like someone reached into my chest and ripped my heart out.My husband and I decided that an amniocentesis was needed for a positive diagnosis and this was arranged for the following day. Studiously the sonographer performed the diagnostic ultrasound with a furrow across his brow. Watching the monitor I saw my baby moving as I watched the colours of red and blue flow through the heart and heard the regular, fast rhythm of the heartbeat. Quietly I hoped that the news was good but the creased brow had told me otherwise. Holding the amniotic fluid in his right hand the sonographer had glanced from it to me and empathetically informed me that the news wasn't good and that he didn't need to send the sample off for a positive diagnosis. Once again my world was crashing and all I wanted to do was bury my head in a pillow and sob. The following weekend dragged and had been filled with streams of tears and emotional turmoil. All I wanted to …. (shrink)

In What is Philosophy?, Deleuze and Guattari make the claim that ‘[i]t may be that believing in this world, in this life, becomes our most difficult task, or the task of a mode of existence still to be discovered on our plane of immanence today. This is the empiricist conversion.’ What are we to make of such a calling? The paper explicates why and in what sense this statement is of exemplary significance both for an appropriate understanding of Deleuze's political (...) thought and for a most timely conceptualisation of politics in a world so clearly defined by immanence, and nothing but immanence. I argue that Deleuze's rigorously constructive approach to the world is not beyond politics, as some recent readings have declared. Rather, we have to appreciate that in Deleuze and Guattari's demand for a ‘belief in this world’ the political intersects with the dimension of the ethical in such a way that our understanding of both is transformed. Only after this ‘empiricist conversion’ can we truly think of a Deleuzian politics that does justice to a plane of immanence ‘immanent only to itself’. (shrink)

For the first time in his Doctrine of Right, Kant employs an expanded, three dimensional concept of public law. In addition to constitutional law, it also includes international law and cosmopolitan law. Each of these concepts of law is assigned its own principle of reason: constitutional law declares that a republic is the only rightful constitution for an individual state; international law requires at least an association of states with higher level instruments of coercion; and cosmopolitan law primarily defines the (...) basic rights of stateless peoples or individuals with respect to existing states. For the principles of reason for constitutional and international law, Kant formulates permissive laws, which allow for imperfections in an effort to promote the optima which the legal principles of reason dictate. Kant justifies these less perfect solutions not only with pragmatic considerations but also with reasons relating to the theory of the sovereignty of nations. Kants Rechtslehre verwendet erstmals einen erweiterten, dreidimensionalen Begriff des öffentlichen Rechts, der neben dem Staatsrecht nun auch das Völkerrecht und das Weltbürgerrecht umfaßt. Jeder dieser Begriffssphären wird ein eigenes vernunftrechtliches Prinzip zugeordnet: das Staatsrecht erklärt die Republik zur einzig rechtmäßigen Verfassung, während das Völkerrecht mindestens eine Staatenassoziation mit höherstufiger Zwangsgewalt erfordert und das Weltbürgerrecht in der Hauptsache die elementaren Rechte von staatslosen Völkern oder Einzelpersonen gegenüber Staaten definiert. Für das staatsrechtliche und das völkerrechtliche Prinzip formuliert Kant Erlaubnisgesetze, die zur Beförderung der vernunftrechtlichen Optima Minderformen zulassen, zu deren Rechtfertigung Kant nicht allein pragmatische, sondern ebenso volkssouveränitätstheoretische Gründe anführt. (shrink)

Kant wird normalerweise zu den 'doktrinären' Begründern des rein-parlamentarischen Demokratiemodells gerechnet; schließlich habe er, nicht zuletzt veranlaßt durch den Jakobiner-Terror, die reine Demokratie als Despotie erkannt und im Gegenzug allein die repräsentative Demokratie als mit den Freiheitsrechten vereinbar gewertet. Diese populäre Ansicht bezweifelt Ulrich Thiele in der vorliegenden Veröffentlichung. Er zeigt auf, daß Kant, von Rousseau inspiriert, eine mehrdimensionale Theorie der demokratischen Gesetzgebung entworfen hat, die sowohl parlamentarische als auch plebiszitäre Verfahren zu ihrem Recht kommen läßt.Wenn Kant sagt, die Demokratie (...) »im eigentlichen Verstande des Worts [sei] notwendig ein Despotism«, so ist, wie schon bei Rousseau, das Modell der griechischen Antike gemeint, und es soll zum Ausdruck gebracht werden, daß eine freiheitsrechtliche Demokratie unabdingbar auf strikte Gewaltenteilung angewiesen sei. Die häufig zitierte Formel von der 'despotischen Demokratie' richtet sich demnach nicht gegen Plebiszite, sondern gegen gewaltenverschmelzende Verfassungen.Wo sich Kant dagegen zugunsten der repräsentativdemokratischen Gesetzgebung ausspricht, geschieht dies durchweg unter Hinweis auf Zweckmäßigkeitserwägungen, nicht aber in der Form eines kategorischen praktischen Urteils. Dieser Befund bestätigt sich, wenn man die Kantische Verwendung der Begriffe Staatsform, Regierungsform und Regierungsart näher untersucht. Nicht die unmittelbare Volksgesetzgebung, sondern allein die demokratische Regierungsform widerspricht der republikanischen, d. h. rechtsstaatlichen Regierungsart, weil dort, wo das Volk die exekutive Gewalt (im weiteren Sinne) ausübe, jeder individuelle Rechtsschutz untergraben werde. Die Anwendung staatlichen Zwanges hinge nämlich nicht von Gesetzen, sondern von zufälligen Mehrheitsentscheidungen ab. (shrink)

Winning isn't everything. It's the only thing. Vince Lombardi The most important thing in the Olympic Games is not to win but to take part, just as the most important thing in life is not the triumph but the struggle. The essential thing is not to have conquered, but to have fought well. The Olympic Creed These two statements reflect two very different approaches to sport. The Lombardi quote reflects the view that we should take a win-at-all-costs approach. By contrast, (...) the Olympic Creed includes the idea that there is something more important in sport than victory. Perhaps the Olympic Creed is correct, and Lombardi mistaken. Perhaps the value of winning is found primarily in its potential to foster both athletic and moral excellence, while the overvaluing of victory for its own sake suffers from several deficiencies as an approach to sport. (shrink)

Often a division of concepts can help us better understand unknown or seldom charted philosophical terrain: historically, the distinctions and differences between idealism and materialism have proven helpful, but with Quentin Meillassoux‟s concept of correlationism, the divisions between realism and anti realismwhich once seemed clean-cut are now harder to understand. Graham Harman has gone a step further than Meillassoux‟s initial definition of correlationism, by which “we mean the idea according to which we only ever have access to the correlation between (...) thinking and being, and never to either term considered apart from the other,”2claiming in lectures that those who have pledged fidelity to the realism banner after Meillassoux aren‟t realist enough.Instead, says Harman, we should demand that any philosophy which claims to be realist must grant that no entity is more real than any other, whether they be atoms, quarks, institutions, regimes, human beings, bonobos, dreams or distant galaxies. A robust realism must maintain therefore that the universe is composed of objects of all shapes, sizes and types. It is here that I wish to stage something of an intervention; it seems to me that we could rather create a new division to help us understand the contemporary situation facing philosophy based on how various philosophies view objects. I propose that we contrast those philosophies which see objects only working through exterior means with those which grant some level of autonomy to objects; in other words, we should compare those philosophies which grant only an outer life to objects withthose which also grant them an inner life. A robust realism must not only count objects as means of our causal ends , or billiard balls in an extended chain of causation . Rather, a full-blown realism must look to the inner lives of objectsto understand the cosmos and not simply satisfy itself with studying their effects.By making this distinction, we can see more clearly the relevance of a number offigures who have yet to be regarded with any seriousness by the emerging speculative realism movement, creating another metaphysical option besidesweak and strong correlationism, eliminative materialism or idealism, speculative materialism and object-oriented philosophy, as well as better understand thefuture of speculative metaphysics. (shrink)

J. L. Austin (1911-1960) exercised in Post-war Oxford an intellectual authority similar to that of Wittgenstein in Cambridge. Although he completed no books of his own and published only seven papers, Austin became through lectures and talks one of the acknowledged leaders in what is called ‘Oxford philosophy’ or ‘ordinary language philosophy’. Few would dispute that among analytic philosophers Austin stands out as a great and original philosophical genius. Three volumes of his writing, published after his death, (...) have become classics in analytical philosophy: Philosophical Papers ; Sense and Sensibilia ; and How to Do Things with Words . First published in 1969, this book is a collection of critical essays on Austin’s philosophy written by well-known philosophers, many of whom knew Austin personally. A number of essays included were especially written for this volume, but the majority have appeared previously in various journals or books, not all easy to obtain. (shrink)

JL Austin exercised in Post-war Oxford an intellectual authority similar to that of Wittgenstein in Cambridge. Although he completed no books of his own and published only seven papers, Austin became through lectures and talks one of the acknowledged leaders in what is called ‘Oxford philosophy’ or ‘ordinary language philosophy’. Few would dispute that among analytic philosophers Austin stands out as a great and original philosophical genius. Three volumes of his writing, published after his death, have become (...) classics in analytical philosophy: _Philosophical Papers_; _Sense and Sensibilia_; and _How to Do Things with Words_. First published in 1979, this book is a collection of critical essays on Austin’s philosophy written by well-known philosophers, many of whom knew Austin personally. A number of essays included were especially written for this volume, but the majority have appeared previously in various journals or books, not all easy to obtain. (shrink)

The biological sciences have always proven a fertile ground for philosophical analysis, one from which has grown a rich tradition stemming from Aristotle and flowering with Darwin. And although contemporary philosophy is increasingly becoming conceptually entwined with the study of the empirical sciences with the data of the latter now being regularly utilised in the establishment and defence of the frameworks of the former, a practice especially prominent in the philosophy of physics, the development of that tradition hasn’t received the (...) wider attention it so thoroughly deserves. This review will briefly introduce some recent significant topics of debate within the philosophy of biology, focusing on those whose metaphysical themes (in everything from composition to causation) are likely to be of wide-reaching, cross-disciplinary interest. (shrink)

J. L. Austin exercised in Post-war Oxford an intellectual authority similar to that of Wittgenstein in Cambridge. Although he completed no books of his own and published only seven papers, Austin became through lectures and talks one of the acknowledged leaders in what is called 'Oxford philosophy' or 'ordinary language philosophy'. Few would dispute that among analytic philosophers Austin stands out as a great and original philosophical genius. Three volumes of his writing, published after his death, have (...) become classics in analytical philosophy: Philosophical Papers; Sense and Sensibilia; and How to Do Things with Words. First published in 1969, this book is a collection of critical essays on Austin's philosophy written by well-known philosophers, many of whom knew Austin personally. A number of essays included were especially written for this volume, but the majority have appeared previously in various journals or books, not all easy to obtain. (shrink)

Winning isn't everything. It's the only thing. Vince Lombardi The most important thing in the Olympic Games is not to win but to take part, just as the most important thing in life is not the triumph but the struggle. The essential thing is not to have conquered, but to have fought well.

This chapter contains sections titled: A Runner is Born A Runner's Conversion to Cycling A Few Lessons from a Relatively New Convert The End of the Tour Notes.