Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, (...) and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. PTEN is a guardian of the genome. However, the role of PTEN in guarding the genome has not been revealed until recently. PTEN controls multiple fundamental processes of genomic transmission. By physically interacting with key molecules in DNA replication, DNA repair/decatenation, and chromosome segregation during the cell cycle, PTEN maintains genomicintegrity and fitness. (shrink)

The object of this article is to examine, with the work of Jeremy Bentham as the principal example, one strand in the complex pattern of European social theory during the second half of the eighteenth century. This was of course the period not only of the American and French revolutions, but of the culmination of the movements of thought constituting what we know as the Enlightenment. Like all great historical episodes, the Enlightenment was both the fulfilment of long-established processes and (...) the inauguration of new processes of which the fulfilment lay in the future. Thus the seminal ideas of seventeenth-century rationalism realized and perhaps exhausted their potentialities in the eighteenth-century Enlightenment. The ideas with which this article is concerned, however—conveniently grouped and labelled as the ideas of utilitarianism—only began to achieve systematic development in these later decades of the eighteenth century. Within that period—during the first half and more of Bentham's long life—attempts to apply those ideas to the solution of social problems met largely with failure and frustration. Yet unrealized potentialities remained, the realization of which was reserved for a time when the world of the philosophes no longer existed. The movements for social and political reform which have played so large a part in modern history since the French Revolution may be judged in widely differing ways; but whatever the verdict, these movements surely cannot be understood without due consideration of that part of their origins which lies in eighteenth-century utilitarianism. (shrink)

What makes something an embryo—as opposed to what is actually, and not just in biotech parlance, a collection of cells? This question has come to the fore in recent years with proposals for producing embryonic stem cells for research. While some of those opposed to use of standard embryonic stem cells emphasise that adult cells have a clinical track record, others argue that there may be further benefits obtainable from cells very like those of embryos, provided such cells can be (...) derived in new ways. Rather than deriving them in ways that kill or otherwise endanger a living human embryo, they could be obtained from an entity that merely resembles a human embryo sufficiently closely for its cells to be of use. Such an entity might be created after introducing genetic changes to an ovum before it is activated by, for example, a cloning-type procedure, such that a gene essential to embryogenesis will be either absent, blocked in its expression, or overexpressed.1,2 The claim is that the ovum could be made to give rise to embryonic stem cells—mere living parts—without ever giving rise to a whole embryo, who is killed to obtain them. Whereas cloning “proper” winds back the specialisation of the cell nucleus to a point where a whole embryo is formed who has not yet specialised its cells, oocyte-assisted reprogramming , it is claimed, would wind back the specialisation merely to an intermediate point at which no embryo is created. Other methods proposed for deriving pseudoembryonic cells include parthenogenesis, in which an ovum is activated without a sperm, or even the insertion of an adult cell nucleus.1MORAL STATUS OF THE EMBRYOIn this paper, I assume that a genuine …. (shrink)

Methoden. Im obigen Artikel ist die „Phylogenie des Stammbaumes” untersucht worden. Beginnend mitHaeckel werden 26 Typen phylogenetischer Symbole kritisch besprochen, d.h. nicht die Resultate, sondern nur die Methoden, z.B. bezüglich Systematik und Phylogenie, lebender und ausgestorbener Organismen, geologischer Perioden, Stufen und homologer Variationen, geographischer Verbreitung, Diversität, etwaiger Bedeutung der Einzelheiten, Mono-, Bi- und Polyrheithrie , usw. Der Faktor Zeit wird dabei für phylogenetische Systeme als der wesentlichste betrachtet. Der Autor hat daher in seinen- neuen Darstellungen die Begriffe „Zeit-Stufen” oder „Zeit-Globen-Oberflächen” (...) eingeführt; diese stehen senkrecht zum „Zeit-Radius”. Auf diesem Grunde wird ein neues Kriterium zur Unterscheidung systematischer und phylogenetischer Vorstellungen denjenigen anderer Autoren hinzugefügt. Erläuterungen. Nach einer Übersicht über die besprochenen Schemen im 1. Teil werden die Verhältnisse zwischen systematischen und phylogenetischen Darstellungen sowie die Verbindung ihrer Symbole untersucht. Es wird gezeigt, dass viele Einzelheiten solcher Konstruktionen oft, wissentlich oder unwissentlich, keine bestimmte Bedeutung haben. Der Verfasser hat versucht zu zeigen, dass es erwünscht wäre, möglichst mit allen Einzelheiten einer symbolischen Darstellung irgendeine Bedeutung zu verbinden: Linien und Entfernungen in der Ebene, Winkel in räumlichen Schemen. Die letztgenannten werden besonders für solche Arten von phylogenetischen Systemen empfohlen, bei denen der Faktor Zeit stets eine der Dimensionen bildet. Dieser Grundsatz wird mit der Evolution systematischer Einzelheiten in Verbindung gebracht, und Merkmals-Phyletik, homologe Variationen, Stufen, Polyrheithrie, Analogie und Homologie, Konvergenz und Verwandtschaft, etc. werden kurz im Lichte der Vererbungslehre besprochen. Es istHayata's extrem dynamischen Ansichten zu verdanken, dass das Statische in den systematischen und phylogenetischen Darstellungen aufgelockert worden ist. Méthodes. Dans l'article inséré ci-dessus il s'agit de ce qu'on pourrait appeler „la phylogénie de l'arbre généalogique”. En commençant parHaeckel , l'auteur discute 26 types divers de symboles phylogénétiques, c.à.d. seulement les méthodes , par exemple en ce qui concerne la taxonomie et la phylogénie, les organismes récents et éteints, les périodes géologiques, les niveaux et les variations homologues, la distribution géographique, la diversité, la signification éventuelle des détails, la mono-, bi- et polyrheithrie , etc. Le Temps est considéré comme l'élément le plus essentiel dans tout système phylogénétique. Par conséquence, l'auteur a introduit dans ses nouvelles représentations les idées de „Niveaux” ou de „Surfaces des Sphères du Temps” qui sont imaginés perpendiculaires au Radius-Temps. Dans l'ordre de ces idées un nouveau critère est ajouté à ceux donnés par d'autres auteurs pour la distinction des systèmes taxonomiques et des représentations phylogénétiques. Justifications. Après une récapitulation des systèmes, énumérés dans la première partie, les relations des constructions taxonomiques et phylogénétiques, ainsi que les connections de leurs symboles sont discutées. Souvent plusieurs détails sont, sciemment ou insciemment, dépourvus de toutes signification. L'auteur a essayé de démontrer qu'il serait désirable d'attribuer autant que possible de significations définies au détails d'une représentation symbolique de la nature décrite: aux lignes et aux distances dans le plan, aux angles dans l'espace. Les constructions tridimensionales sont particulièrement recommandées pour plusieurs systèmes phylogénétiques; dans de tels systèmes le Temps devrait toujours remplir la fonction d'une des dimensions. Ce principe est mis en rapport avec l'évolution des unités taxonomiques; phylogénie des charactères, variations homologues, niveaux, polyrheithrie, analogie et homologie, convergence et relations héréditaires, tous ces sujets sont brièvement discutés dans leurs rapports avec la Génétique. Selon l'opinion de l'auteur, c'est aux idées ultra-dynamiques d'Hayata que la taxonomie et la phylogénie doivent la pénétration féconde du dynamisme dans leurs systèmes trop souvent statiques. (shrink)

Cultural boundaries in Islam based on Hadith (Islamic traditions).

David Shaw's response to Hugh McLachlan's criticism of his proposed new perspective on euthanasia is ineffectual, mistaken and unfair. It is false to say that the latter does not present an argument to support his claim that there is a moral difference between killing and letting die. It is not the consequences alone of actions that constitute their moral worth. It can matter too what duties are breached or fulfilled by the particular moral agents who are involved.

H. S. Eveling; XII—Some Patterns of Justification in Ethics, Proceedings of the Aristotelian Society, Volume 66, Issue 1, 1 June 1966, Pages 149–166, https://do.

Study of Islamic philosophy of Yaḥyá ibn Ḥabash Suhrawardī, 1152 or 1153-1191.

SUFFERING HUMAN AND DIVINE INTRODUCTION I KNEW when I asked Dr. H. Wheeler Robinson to write this volume on Suffering that I was giving him the most difficult ...

In the modern world of total technologization, scientific knowledge devoid of worldview correction (humanitarian expertise) carries a threatening tendency of self-denial: without a constant, philosophically correct transformation of objective knowledge about certain fragments (branches) of the surrounding reality into human knowledge (questions) about itself, the practical effectiveness of such knowledge inevitably accumulates in itself the threat of practical helplessness. Aim and the tasks of the research. Based on an in-depth analysis of the category of existence, as well as on modern (...) philosophical reflections on the methodological and cognitive insolvency of the idea of the world, to find out the real meaning of those changes that this idea meaningfully undergoes in the conditions of the modern total technologization of human life. The research methodology. From a methodological point of view, the author prefers a dialectical approach, considering the analyzed phenomena, regardless of the mode of their reality, in their development and internally contradictory essence. H. Plesner’s theory of eccentric positionality serves as a certain base point for the analysis of human nature and, accordingly, the world of human existence. Research results: The problematic existence of the world and the epistemological «failure» of the corresponding category, declared in some modern philosophical reflections, are connected exclusively with its anthropological and worldview function, which is based on the fundamental uncertainty of a man’s place in the world. The «worthlessness» («futility») of worldview thematization is derived from the allencompassing inability of the human figure in the world, from that «emptiness» and «invisibility» (specific own transparency) of the spiritual dimension of human existence, on which, however, this existence is based. Discussion. The human «option» of fulfilling the unity of living being can be characterized as extremely intense. In this variant, the phylogenetic line of development turns into an ontogenetic point of worldliness devoid of predetermined content, a fundamentally new type of integration. The horizons of such integration far exceed primarily because of its understanding. And the subject of such a meaningful life is forced to integrate everything that happens to him every time into a certain system (synthesis) of the world. That subjectivity the world has distinguishes the subject from the thing. Subjectivity and the world mutually belong to each other - they are correlative. A thing exists because it is what it is. The subject (and with it his world) does not exist like that. A subject is how and to what it relates. But the relation «how» and «to what» is not carried out completely anew and isolated every time, but exists in its multiplicity in a certain relationship. Each individual case, each individual action (method of action) acquires its meaning from a wider, structured context – in whole or in part. This context is the «world», the «life world» of the real subject, or the «world» as an anthropological idea. Conclusions. The task of modern humanitarianism is not only to find opportunities for rational use of the fact of the fundamental openness of the human being, but also to cultivate the ability to reconcile a man with himself, to accept himself. This gives us certain reasons to hope for the enduring significance of worldview thematization. Criticism regarding the seemingly paradoxical conclusion that to become a man, one must already be one, could be considered fair, but only if one does not take into account the principled nature of such an aphoristic position, because this is exactly how the human world exists - as the art of tolerance uncertainty. (shrink)

Ṣadr al-Dīn Shīrāzī, Muḥammad ibn Ibrāhīm, -1641--Criticism and interpretation. ; Islamic philosophy.

A collection of essays written in affectionate tribute to Gombrich.

George Herbert Mead's lectures at the University of Chicago are more important to understanding Mead's views on social psychology than some commentators, such as Hans Joas, have emphasized. Mead's 1898-99 lecture series, preserved through the notes of his student H. Heath Bawden, demonstrate his devotion to Hegelianism as a method of thinking and how this influenced his non-reductive approach to functionalist psychology. In addition, Mead's breadth of historical knowledge and his commitments in the natural and social sciences are on display (...) here, culminating in the Darwinian observation that human animals only achieve the degree of control they have over their environment by the achievement of social organization. (shrink)

Contributed articles on Buddhist doctrines and philosophy; festschrift in honor of Narayan Hemandas Samtani, Buddhist scholar.

The energy-spectrum of two point-like particles interacting in a 3-D isotropic Harmonic Oscillator (H.O.) trap is related to the free scattering phase-shifts \(\delta \) of the particles by a formula first published by Busch et al. It is here used to find an expression for the shift of the energy levels, caused by the interaction, rather than the perturbed spectrum itself. In the limit of high energy (large quantum number \(n\) of the H.O.) this shift (in H.O. units) is shown (...) to be given by \(\Delta =-2\frac{\delta }{\pi }\) , also exact in the limit of infinite scattering length ( \(\delta =\pm \frac{\pi }{2}\) ) in which case \(\Delta =\mp 1\) . Numerical investigation shows that this expression otherwise differs from the exact result of Busch et al., by less than \(\frac{1}{2}\,\%\) except for \(n=0\) when it can be as large as \(\approx \) 2.5 %. This result for the energy-shift is well known from another exactly solvable model, namely that of two particles interacting in a spherical infinite square-well trap (or box) of radius \(R\) in the limit \(R\rightarrow \infty \) , and/or in the limit of large energy. It is in solid state physics referred to as Fumi’s theorem. It can be (and has been) used in (infinite) nuclear matter calculations to calculate the two-body effective interaction in situations where in-medium effects can be neglected. It is in this context referred to as the phase-shift approximation a term also used throughout this report. (shrink)

Machine generated contents note: PART I: HEIDEGGER'S FUNDAMENTAL -- ONTOLOGY OF DASEIN -- Section A: Being and Time -- 1 Dasein and the World -- 2 Dasein's Being-in, Care, and Truth -- 3 Dasein and Temporality -- Section B: Heidegger's Rejection of the I-Thou -- 4 Phenomenology and Dasein -- 5 Heidegger's First Critique of the I-Thou -- 6 The I-Thou in Heidegger's Study of Kant -- 7 Metaphysics and Logic -- PART II: BUBER'S I-THOU -- Section A: I and (...) Thou -- 8 First Presentation of the I-Thou -- 9 Living the I-Thou -- Section B: Beyond I and Thou -- 10 The I-Thou and Dialogue -- 11 Buber's Critique of Heidegger -- 12 Conclusion and Some Implications -- Selected Bibliography -- Index. (shrink)

Investigation of a Johannine church/school: Methodological remarks on the course of the case.In an effort to resolve a major facet of the ‘Johannine problem’ scholars assign the distinctiveness of the fourth gospel to its formation allegedly within and for a separate and independent Johannine community (or school). The reconstructions and descriptions of this community are presently assessed by critical scrutiny of the hermeneutical paradigms and exegetical procedures utilized by scholars. So, as is mostly the case within current New Testament science, (...) this debate culminated in controversies on methodology.Opting for real progress and positive results, means that some or other integration/correlation of methods is inevitable. Proper and mutual cognisance must be taken of the vantage points and hermeneutical perceptions with which scholars work. This entails cooperative interaction between all forms of historical exegesis on the one hand, and text immanent exegesis on the other hand. (shrink)

Accent in Hittite: A Study in Plene Spelling, Consonant Gradation, Clitics, and Metrics. By Alwin Kloekhorst. Studien zu den Boğazköy-Texten, vol. 56. Wiesbaden: Harrassowitz Verlag, 2014. Pp. xxv + 716. €98.