Transcriptional silencing may not necessarily depend on the continuous residence of a sequence‐specific repressor at a control element and may act via a “hit and run” mechanism. Due to limitations in assays that detect transcription factor (TF) binding, such as chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq), this phenomenon may be challenging to detect and therefore its prevalence may be underappreciated. To explore this possibility, erythroid gene promoters that are regulated directly by GATA1 in an inducible system are analyzed. It (...) is found that many regulated genes are bound immediately after induction of GATA1 but the residency of GATA1 decreases over time, particularly at repressed genes. Furthermore, it is shown that the repressive mark H3K27me3 is seldom associated with bound repressors, whereas, in contrast, the active (H3K4me3) histone mark is overwhelmingly associated with TF binding. It is hypothesized that during cellular differentiation and development, certain genes are silenced by repressive TFs that subsequently vacate the region. Catching such repressor TFs in the act of silencing via assays such as ChIP‐seq is thus a temporally challenging prospect. The use of inducible systems, epitope tags, and alternative techniques may provide opportunities for detecting elusive “hit and run” transcriptional silencing. Also see the video abstract here https://youtu.be/vgrsoP_HF3g. (shrink)

For paediatric medicine to advance, research must be conducted specifically with children. Concern about poor recruitment has led to debate about payments to child research participants. Although concerns about undue influence by such ‘compensation’ have been expressed, it is useful to determine whether children can relate the time and inconvenience associated with participation to the value of payment offered. This study explores children's ability to determine fair remuneration for research participation, and reviews payments to children participating in research. Forty children (...) were interviewed before outpatient visits at two London Hospitals: Great Ormond Street Children's Hospital and the Whittington Hospital District General Hospital. Children were asked to value their involvement in two hypothetical research scenarios – the first an ‘additional blood sample’, the second also involving daily oral oil capsules taken for a fortnight before further venesection. Background knowledge about familiarity with money, and experience with hospitalisation was assessed. The mean valuation of involvement in the second scenario (£13.18) was higher than in the first (£2.84) (p<0.001). This higher valuation persisted when children were categorised into groups ‘aged 12+’ and ‘below 12’. Those undergoing a blood test on the day placed a higher valuation on participation in the second scenario (£10.43, £21.67, p=0.044). These children aged 8–16 demonstrated the capacity to discern a fair valuation for participation in medical research. The monetary sums are influenced by the time and inconvenience involved in the research, and by the extent of recent experience with hospital procedures. The authors review current ethical thinking regarding payments to child research participants and suggest that a fair wage model might be an ethically acceptable way to increase participation of children in research. (shrink)

Small-scale research projects involving human subjects have been identified as being effective in developing critical appraisal skills in undergraduate students. In deciding whether to grant ethical approval to such projects, university research ethics committees must weigh the benefits of the research against the risk of harm or discomfort to the participants. As the learning objectives associated with student research can be met without the need for human subjects, the benefit associated with training new healthcare professionals cannot, in itself, justify such (...) risks. The outputs of research must be shared with the wider scientific community if it is to influence future practice. Our survey of 19 UK universities indicates that undergraduate dissertations associated with the disciplines of medicine, dentistry and pharmacy are not routinely retained in their library catalogues, thus closing a major avenue to the dissemination of their findings. If such research is unlikely to be published in a peer-reviewed journal, presented at a conference, or otherwise made available to other researchers, then the risks of harm, discomfort or inconvenience to participants are unlikely to be offset by societal benefits. Ethics committees should be satisfied that undergraduate research will be funnelled into further research that is likely to inform clinical practice before granting ethical approval. (shrink)

Ancient schematic systems originating in the Jewish and Chinese traditions that demonstrate dynamic integration of human consciousness with the material world offer fresh insights into the process through which technoetic art forms are created at the intersections of art, science, technology, and culture. Kabbalah is Judaism's esoteric tradition that reveals the deep structure of biblical consciousness through a symbolic language, conceptual schema, and graphic model for exploring the creative process. The Tree of Life schema is a network of 22 pathways (...) linking 10 nodes (sephirot) that represent stages in the creative process. The first three sephirot represent the artist's undifferentiated intention to create and the cognitive dyad in which a flash of insight begins to crystallize into a viable idea. Two affective dyads, largess/restraint and success/gracefulness, are balanced by the sephirah (singular for sephirot) of Beauty, the aesthetic heart of the entire process. The ninth sephirah funnels the integrated flow of intention, thought, and emotion into the world of physical action that is the tenth sephirah. The Kabbalistic schema is used to trace the process of creating Inside/Outside: P'nim/Panim, a technoetic moist- media artwork in which a biofeedback imaging system forms a feedback loop between changing mind/body processes and corresponding changes in digital self-portraits. (shrink)

In recent years, many philosophers of modern physics came to the conclusion that the problem of how objectivity is constituted (rather than merely given) can no longer be avoided, and therefore that a transcendental approach in the spirit of Kant is now philosophically relevant. The usual excuse for skipping this task is that the historical form given by Kant to transcendental epistemology has been challenged by Relativity and Quantum Physics. However, the true challenge is not to force modern physics into (...) a rigidly construed static version of Kant's philosophy, but to provide Kant's method with flexibility and generality. In this book, the top specialists of the field pin down the methodological core of transcendental epistemology that must be used in order to throw light on the foundations of modern physics. First, the basic tools Kant used for his transcendental reading of Newtonian Mechanics are examined, and then early transcendental approaches of Relativistic and Quantum Physics are revisited. Transcendental procedures are also applied to contemporary physics, and this renewed transcendental interpretation is finally compared with structural realism and constructive empiricism. The book will be of interest to scientists, historians and philosophers who are involved in the foundational problems of modern physics. (shrink)

P. Kyle Stanford - The Manifest Connection: Causation, Meaning, and David Hume - Journal of the History of Philosophy 40:3 Journal of the History of Philosophy 40.3 339-360 The Manifest Connection: Causation, Meaning, and David Hume P. Kyle Stanford 1. Introduction exciting recent hume scholarship has challenged the traditional view that Hume's theory of meaning leads him to deny the very intelligibility or coherence of supposing that there are objective causal powers or intrinsic necessary connections between causally related entities. Influential (...) recent interpretations have variously held that Hume himself accepted the existence of such powers and connections, that he was genuinely agnostic about them, or that he denied their existence while nonetheless holding it to be a perfectly coherent possibility, indeed one that we routinely think actual. In this paper I will argue against all three of these lines of interpretation and in favor of what I consider a neglected alternative: that Hume rejects the existence of objective necessary connections or causal powers as literally incoherent or meaningless, but on subtle and sophisticated semantic grounds, rather than simplistic ones. I find support for this semantic reading and against the alternatives not only in passages whose significance to the debate is widely appreciated, but also in Hume's discussions "Of Liberty and Necessity" and "Of the Immateriality of the Soul." The.. (shrink)

Equipoise is advocated as a means of achieving high scientific and ethical standards in randomised trials. As used in the context of research the word describes a state of uncertainty characterised by the belief that in a trial no arm is known to offer greater harm or benefit than any other arm. Clinicians who lack personal equipoise are advised to accept clinical or communal equipoise, based on current unresolved disagreement among the medical profession. Equipoise is mainly discussed in the literature (...) as an issue for senior doctors and research directors. Limitations of professional equipoise are reviewed, and data on the neglected topic of patients' equipoise are reported using the example of breast cancer trials. In theory, a patient who gives informed and voluntary consent to enter a randomised trial has achieved the equilibrium of equipoise. In practice, equipoise among patients ranges from personal to proxy acceptance. (shrink)

I contrast our own evidence for the hypothesis of organic fossil origins with that available in previous centuries, suggesting that the most powerful contemporary evidence consists in a form of projective support whose distinctive features are not well captured by familiar hypothetico-deductive, abductive, or even more recent and more technically sophisticated accounts of scientific confirmation. I suggest that such accounts either misrepresent or ignore something important about the heterogeneous ways in which scientific hypotheses can be supported by evidence, and I (...) go on to suggest that the search for any single such account may be misguided in any case. (shrink)

We locate winning strategies for various ${\mathrm{\Sigma }}_{3}^{0}$ -games in the L-hierarchy in order to prove the following: Theorem 1. KP+Σ₂-Comprehension $\vdash \exists \alpha L_{\alpha}\ models"\Sigma _{2}-{\bf KP}+\Sigma _{3}^{0}-\text{Determinacy}."$ Alternatively: ${\mathrm{\Pi }}_{3}^{1}\text{\hspace{0.17em}}-{\mathrm{C}\mathrm{A}}_{0}\phantom{\rule{0ex}{0ex}}$ "there is a β-model of ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}\text{\hspace{0.17em}}\text{\hspace{0.17em}}+\text{\hspace{0.17 em}}{\mathrm{\Sigma }}_{3}^{0}$ -Determinacy." The implication is not reversible. (The antecedent here may be replaced with ${\mathrm{\Pi }}_{3}^{1}\text{\hspace{0.17em}}\text{\hspace{0.17em}}\left({\mathrm{\Pi }}_{3}^{1}\right)-{\mathrm{C}\mathrm{A}}_{0}:\text{\hspace{0.17em}}{\mathrm{\Pi }}_{3}^{1}$ instances of Comprehension with only ${\mathrm{\Pi }}_{3}^{1}$ -lightface definable parameters—or even weaker theories.) Theorem 2. KP +Δ₂-Comprehension +Σ₂-Replacement + ${\mathrm{\Sigma }}_{3}^{0}\phantom{\rule{0ex}{0ex}}$ -Determinacy. (Here AQI (...) is the assertion that every arithmetical quasi-inductive definition converges.) Alternatively: $\Delta _{3}^{1}{\rm CA}_{0}+{\rm AQI}\nvdash \Sigma _{3}^{0}$ -Determinacy. Hence the theories: ${\mathrm{\Pi }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0},\text{\hspace{0.17em}}{\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}+\text{\hspace{0.17em}}{\mathrm{\Sigma }}_{3}^{0}-\mathrm{D}\mathrm{e}\mathrm{t}\phantom{\rule{0ex}{0ex}}$ -Det, ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}+\mathrm{A}\mathrm{Q}\mathrm{I}$ , and ${\mathrm{\Delta }}_{3}^{1}-{\mathrm{C}\mathrm{A}}_{0}\phantom{\rule{0ex}{0ex}}$ are in strictly descending order of strength. (shrink)

The author clarifies the existential philosophy that is implicit in Kurt Goldstein's philosophy of organism (Goldstein, 1963; 1995). Situated in response to the growing trend that psychological phenomena are reducible to the nervous system, the author argues for the reverse: that the significance of nervous system activity can only be understood by viewing it as background to foreground performances. Like the organization of perception into meaningful figure-- ground Gestalts, the existential modes of embodiment, sociality, temporality, spatiality, and attunement are organized (...) together to accomplish foreground performances. It is only within this context that the activity of the nervous system may be understood as significant or insignificant. Speech is given as an example. The article concludes with a commentary on how the trend of reducing psychological phenomena to neurological phenomena has impaired our understanding of brain disorders and psychological disorders. (shrink)

In the axiomatic development of the logic of nonrelativistic quantum mechanics it is not difficult to set down certain plausible axioms which ensure that the quantum logic of propositions has the structure of an orthomodular poset. This can be done in a number of ways, for example, as in Gunson [2], Mackey [4], Piron [5], Varadarajan [7] and Zierler [8], and we summarise one of these ways in §2 below.

The aim of this study is to analyse the effect of religiosity on psychological well-being via meta-analytical method. In addition, the presence of moderator variables that may cause the influence quantity which was calculated as a result of meta-analytical process, is analysed. For these aims, studies that are suitable for the criterion of choice were identified. Within this context, without applying a criterion for date, the influence quantity of 10 thesis studies were calculated, which analyse the correlation between religiosity and (...) psychological well-being, and which include the number of samples used in meta-analysis and the number of pearson correlation coefficient (r) valu. Regarding the theses included in this study, 3 (30%) of them doctoral theses and 7(70%) of them are master’s theses. The number of people in samples is 5.914, 3.848 (65,06%) of which are from doctoral, and 2.066 (34,94%) of which are from master’s theses. For the analysis of the data, CMA (Comprehensive Meta-Analysis 2.0) statistical package program was used. The publication bias of the researches covered in this study was analysed via “Funnel Plot Graphic”, “Classic fail-safe N”, “Begg and Mazumdar rank correlations” and “Egger’s regression test” statistics methods. As a result of these statistical analyses, no evidence of publication bias has been found. Heterogeneity test was conducted to identify which model is to be used in measuring the influence quantity of the researches included in the study. The Q(sd=9) statistical value for its heterogeneity was measured as 114,90 (p0,05). According to this, it was concluded that the sample groups in the studies covered in the meta-analysis did not have a moderator role in the relationship between religiosity and psychological well-being. In addition, the average influence quantity for scientific publication types in Fisher’s z is respectively.193 for PhD, and.118 for master’s degree. The average influence quantity for these subsample groups was not considered to be statistically significant (QB=0,384; p>0,05), either. In other words, the type of publication does not play a moderator role in the relationship between religiosity and psychological well-being. (shrink)

It is the purpose of this note to comment on some important problems which have been already vividly discussed by several authors. Besides the well known former discussions of Schrödinger and J. v. Neumann I should like to mention here especially H. Margenau's article, “Critical Points in Modern Physical Theory,” which strongly influenced my present discussion.

This paper deals with three topics: types of rights, the development of the terminology of rights, and the question of the primacy of welfare rights. Because these topics are interrelated, my exposition does not observe rigid boundaries among them. There is no pretence at all that any of these subjects is fully covered here; nor is it proposed, except for one writer, to touch upon the contemporary literature on rights, as noteworthy as some of that literature is. In order to (...) gain entrance into the field, on which the writing has grown to massive proportions, I shall begin with an interesting historical phenomenon, some of whose philosophical import I want to explore. I should say at the outset, however, that the general motivation of this paper is the problem of the significance of the language of “rights.” Does it really make a difference, for instance, to speak of the “rights of man” rather than the “common duties of humanity”? Does the term “rights” add anything of special significance or is its only significance rhetorical and ideological? Can we dispense with the language of rights and still say everything we need to say about our moral relations? I confess to a moderate skepticism about the necessity of the language of rights in the last analysis. At any rate, this paper is intended as a contribution, however small, to this problem. The historical phenomenon with which I am going to begin will enable us to bring into focus the issue of the meaning of “rights.”. (shrink)

Children's competence to refuse or consent to medical treatment or surgery tends to be discussed in terms of the child's ability or maturity. This paper argues that the social context also powerfully influences the child's capacity to consent. Inner attributes and external influences are discussed using an analogy of the genes and the stars.

This article explores the influence of Stoicism and religion on Adam Smith. While other commentators have argued either that the main influence on Smith was Stoicism or that it was religion, the two influences have not been explicitly linked. In this article I attempt to make such a link, arguing that Smith can be seen as belonging to the strand of Christian Stoicism chiefly associated with his teacher, Francis Hutcheson. Finally, some comments are made about the implications of this interpretation (...) for current understanding of the work of Adam Smith. (shrink)

Several cases which have been considered by the courts in recent years have highlighted the legal dilemmas facing doctors whose decisions result in the ending of a patient's life. This paper considers the case of Dr Cox, who was convicted of attempting to murder one of his patients, and explores the roles of motive, diminished responsibility and consent in cases of "mercy killing". The Cox decision is compared to that of Tony Bland and Janet Johnstone, in which the patients were (...) in a persistent vegetative state. In all three cases, the doctors believed that their patients' quality of life was so poor that their continued existence was of no benefit to them, and decided that their lives should not be unduly prolonged, yet the doctor who was prosecuted was the one whose dying patient had requested that her death be hastened. The paper examines the law's seemingly contradictory approaches to such cases. (shrink)

Ce travail pose la question des critères de la „progression biologique“ , d'après les documents fossiles, dans le monde des organismes, c'est-à-dire de ce perfectionnement qui ne s'arrête pas à l'intérieur du cadre d'un phylum donné, comme le „perfectionnement de l'adaptation“, mais qui conduit, au-de-là de phylums de rang différent, à des types supérieurs, par exemple, des Poissons pas les Amphibies et les Reptiles jusqu'aux Mammifères ou aux Oiseaux. Deux groupes de critères y sont recensés en détail, leur contenu est (...) exposé, et on les examine pour voir s'ils caractérisent sans ambiguïté la „progression biologique“. Le premier groupe comprend les critères de „différenciation croissante“ et „d'intégration harmonique”. Ils sont fondés sur la différenciation morphophysiologique ou plus exactement sur la „totalité” des organismes, c'est-à-dire leur multiplicité dans l'unité. Le second groupe de critères, à savoir „indépendance croissante du milieu” et „autonomie individuelle croissante”, part des relations de l'organisme au milieu et aux autres formes vivantes et souligne la „subsistence” des individus, c'est-à-dire leur plus ou moins grande indépendence ou leur stabilité interne. Comme „totalité” et „subsistence” sont les éléments décisifs d'une définition biologique de l'individu, on peut dire que la „progression biologique“ d'un organisme est d'autant plus élevée que sa totalité et subsistence et par là son être individuel sont plus accusés.Tous les critères mentionnés ne sont pas uniformes. Les motifs de leur imprécision sont divers. Tout d'abord, il n'y a pas encore de définition unique et complète de l'individu biologique, de sorte qu'on ne peut circonscrire d'une manière univoque ce qui confère à un organisme une individualité plus forte ou moins forte. Ensuite les lignées au-delà desquelles s'accomplissent des perfectionnements, et dont l'une reste intérieur au phylum , tandis que l'autre le transcende , sont entrelacées si intimement et d'une façon si particulière qu'elles ne se laissent pas séparer franchement et décrire rigoureusement selon leurs signes distinctifs. Tout représentant d'un phylum, peu importe son palier, est en effet nécessairement inséré dans un milieu et en quelque façon spécialisé. Il n'existe pas des types à caractères phylétiques purs, qui ne montrent dans aucune direction un „perfectionnement de l'adaptation”, mais seulement des marques caractéristiques de la „progression biologique”. Enfin nous ne connaissons pas les restes fossiles que le développement ou la formation des grands phylums du règne animal, à savoir du rameau des Vertébrés et des divers groupes des Invertébrés, mais non pas le plus intéressant et le plus important, leur „progression biologique” jusqu'au degré d'organisation qu'ils présentent déjà à l'époque du Silurien ou plutôt du Cambrien. C'est cela seulement qui permettrait une vue plus profonde sur la nature de la „progression biologique”.Die Arbeit stellt die Frage nach den Kriterien des fossil belegten Biologischen Aufstiegs” der Organismenwelt, d.h. derjenigen Vervollkommnung, die sich nicht innerhalb des Rahmens eines gegebenen Bauplans hält, wie die „Anpassungsvervollkommnung”, sondern über verschiedenrangige Baupläne hinweg zu höheren Typen führt, z.B. von den Fischen über die Amphibien und Reptilien zu den Säugern bzw. Vögeln. Ausführlich werden zwei Gruppen von Kriterien besprochen, ihr Inhalt dargelegt und ihre Eindeutigkeit zur Charakterisierung des „Biologischen Aufstiegs” untersucht. Die erste Gruppe umfasst die Kriterien der „zunehmenden Differenzierung” und „harmonischeren Integration”. Diese legen die morphologisch-physiologische Differenzierung oder genauer die „Ganzheit” der Organismen zugrunde, d.h. ihre Vielheit in der Einheit. Die zweite Kriteriengruppe, nämlich „zunehmende Umweltunabhängigkeit” und „zunehmende individuelle Autonomie”, geht von den Beziehungen des Organismus zur Umwelt und zu andern Lebensformen aus und betont die „Subsistenz” der Individuen, d.h. ihr grösseres oder geringeres Losgelöstsein oder ihre Selbständigkeit. Da nun „Ganzheit” und „Subsistenz” die entscheidenden Elemente einer biologischen Definition des Individuums sind, lässt sich sagen, dass der „Biologische Aufstieg” eines Organismus um so höher ist, je stärker seine Ganzheit und Subsistenz und damit sein Individuumsein ist.Eindeutigkeit kommt allen genannten Kriterien nicht zu. Die Gründe für ihre Unschärfe sind verschiedener Art. Zunächst gibt es noch keine eindeutige und vollständige Definition des biologischen Individuums, so dass sich nicht eindeutig umreissen lässt, was einem Organismus eine stärkere oder weniger starke Individualität verleiht. Dann sind die Linien, über die sich Vervollkommnungen vollziehen und von denen die eine innerhalb des Bauplans bleibt , die andere aber über ihn hinausführt so innig und in so eigenartiger Weise miteinander verflochten, dass sie sich nicht sauber scheiden und in ihren charakteristischen Merkmalen genau beschreiben lassen. Jeder Vertreter eines Bauplans, ganz gleich von welcher Ranghöhe, ist nämlich notwendig in eine Umwelt eingepasst und irgendwie spezialisiert. Es gibt keine Typen mit reinen Bauplanmerkmalen, die nach keiner Richtung hin eine „Anpassungsvervollkommnung”, sondern nur Merkmale des „Biologischen Aufstiegs” aufweisen. Schliesslich kennen wir fossil nur die Entfaltung oder Ausgestaltung der Grossbaupläne des Tierreichs, nämlich des Wirbeltierstammes und der verschiedenen Gruppen der Wirbellosen, nicht aber das Interessanteste und Wichtigste, nämlich ihren „Biologischen Aufstieg” zu der organisatorischen Höhe, mit der sie sich im Silur bzw. im Kabrium bereits vorstellen. Das erst würde einen tieferen Einblick in das Wesen des „Biologischen Aufstiegs” vermitteln.This article deals with the question of the criteria for the “biological ascent” of the organic world, resting on fossil evidence. That is, of that improvement which is not only restricted to the framework of a given “general structure” as is the “improvement of adaptation”, but which also leads beyond general structures of differentiated levels to a higher type,e.g. from the fishes through the amphibians and reptiles to the mammals or birds. Two groups of criteria are discussed at length, their content exposed and their univocity for the characterisation of this “biological ascent” is examined. The first group includes the criteria of “increasing differentiation” and “more harmonious integration”. The basis for these is the morphological-physiological differentiation, or more exactly, the “totality” of the organisms,i.e., their variety-in-unity. The second group of criteria, “increasing independence of environment” and “increasing individual autonomy”, is derived from the relationships of the organism to its environment and to other living forms, and stresses the “subsistence” of individuals,i.e., their greater or lesser degree of independence or self-sufficiency. Now since “totality” and “subsistence” are the decisive elements in a biological definition of the individual, it may be said that the “biological ascent” of an organism is higher, the more perfect its totality and subsistence and therefore its individuality is.The criteria mentioned are not univocal. The reasons for this lack of clarity are varied. First of all, there is no univocal and complete definition of the biological individual, so that it cannot be exactly stated just what gives an organism a more or less perfect individuality. Then the lines, along which improvements are made, and according to which the one remains within the general structure and the other goes beyond the general structure , are so intimately and singularly bound together, that they cannot be cleanly distinguished, and their characteristic notes exactly described. For each representative of a general structure, regardless of its level, is necessarily fitted into an environment and somehow or other specialised. There are no types with only notes of the general structure which show in no direction an “improvment of adaption”, but only the signs of “biological ascent”. Finally, we only have fossil evidence for the development or deployment of the “great general structures” of the animal world, namely that of the vertebrates and of the different groups of invertebrates, not for the most interesting and most important, that is, their “biological ascent” to the level of organisation with which they are found in the Silurian or Cambrian periods. Only that would give us a deeper insight into the essence of “biological ascent”. (shrink)

Reprint. Originally published: Rajini's punchtantra: value statements on business and life management. Chennai: New Horizon Media, 2010.