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)

Early versions of satellite and radiosonde datasets suggested that the tropical surface had warmed more than the troposphere, while climate models consistently showed tropospheric amplification of surface warming in response to human-caused increases in greenhouse gases. We revisit such comparisons here using new observational estimates of surface and tropospheric temperature changes. We find that there is no longer a serious discrepancy between modeled and observed trends in the tropics. Our results contradict a recent claim that all simulated temperature trends in (...) the tropical troposphere are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”.This emerging reconciliation of models and observations has two primary explanations. First, because of changes in the treatment of buoy and satellite information, new surface temperature datasets yield slightly reduced tropical warming relative to earlier versions. Second, recently developed satellite and radiosonde datasets now show larger warming of the tropical lower troposphere. In the case of a new satellite dataset from remote sensing systems, enhancedRSS warming is due to an improved procedure of adjusting for inter-satellite biases. When the RSS-derived tropospheric temperature trend is compared with four different observed estimates of surface temperature change, the surface warming is invariably amplified in the tropical troposphere, consistent with model results. Even if we use data from a second satellite dataset with smaller tropospheric warming than in remote sensing systems RSS, observed tropical lapse rates are not significantly different from those in all model simulations.Our results contradict a recent claim that all simulated temperature trends in the tropical troposphere and in tropical lapse rates are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”. (shrink)

In the October 1937 number of Philosophy of Science Lindsay has made certain criticisms of the adequacy of the “operational method” of analyzing and giving meaning to the concepts of physics, documenting his criticisms chiefly from my own writings. In these criticisms he has made statements as to the method which I would by no means accept. This is not characteristic of his paper only, for I have seldom indeed seen a printed discussion of the method which I would accept (...) as being an adequate or sometimes even fair representation of what I understand by it. It will perhaps pay therefore if I attempt to state what I conceive it to be all about, particularly since I have never attempted such a comprehensive statement and since my own ideas on the subject have been developing since I first wrote in the Logic of Modern Physics. For one reason I have hesitated to do this, for fear of seeming to subscribe to the not uncommon idea that we are dealing with some elaborate and profound new theory of the nature of knowledge or of meaning. I believe that I myself have never talked of “operationalism” or “operationism”, but I have a distaste for these grandiloquent words which imply something more philosophic and esoteric than the simple thing that I see. What we are here concerned with is an observation and description of methods which at least some physicists had already, perhaps unconsciously, adopted and found successful—the practise of the methods already existed. What I have attempted is to analyze these successful methods, not to set up a philosophical system and a theory of the properties that any method must have if it hopes to be successful. Since I was concerned with a technique already extant, my principal method of getting others to see what the technique involved has been to exhibit examples of the technique in action, rather than to attempt any exhaustive characterization of the technique itself. (shrink)

Geared toward readers already acquainted with special relativity, this book transcends the view of theory as a working tool to answer natural questions: What is ...

The difficulties of undertaking good quality effectiveness research in palliative medicine are well documented. Much of the ethical literature in this area focuses on the vulnerability of the palliative care population. It is clear that a wider ethical approach will need to be used to justify research in the terminally ill. Some themes of ethical thought are underutilised in considering the ethics of palliative care research. Three arguments to justify the need for effectiveness research in palliative care should be highlighted: (...) there is evidence of an untapped altruism amongst the population of palliative care patients who would be keen to be involved in such research; traditional Aristotelean and Thomistic virtue ethics would point to the need to gain knowledge in and of itself, but especially in palliative medicine for the benefit of patients: virtue also accrues in the acquisition of a stock of research experience which in turn makes further research feasible; most compellingly, justice would dictate that palliative treatments are effective, that futile or useless treatments are avoided and that patients are not party to “n of 1” trials by default. The current state of the evidence base of effectiveness in palliative care leads us to the uncomfortable position where patients are in precisely the position of being unwitting participants in “n of 1” clinical trials by default, without their explicit consent. (shrink)

Introduction, by G. Holton.--Three eighteenth-century social philosophers: scientific influences on their thought, by H. Guerlac.--Science and the human comedy: Voltaire, by H. Brown.--The seventeenth-century legacy: our mirror of being, by G. de Santillana.--Contemporary science and the contemporary world view, by P. Frank.--The growth of science and the structure of culture, by R. Oppenheimer.--The Freudian conception of man and the continuity of nature, by J. S. Bruner.--Quo vadis, by P. W. Bridgman.--Prospects for a new synthesis: science and the humanities as complementary (...) activities, by C. Morris.--A humanist looks at science, by H. M. Jones. (shrink)

We live in a world of rapidly advancing, revolutionary technologies that are not just reshaping our world and wars, but also creating a host of ethical questions that must be dealt with. But in trying to answer them, we must also explore why exactly is it so hard to have effective discussions about ethics, technology, and war in the first place? This article delves into the all-too-rarely discussed underlying issues that challenge the field of ethics when it comes to talking (...) about war, weapons, and moral conduct. These issues include the difficulty of communicating across fields; the complexity of real world dilemmas versus the seminar room and laboratory; the magnified role that money and funding sources play in shaping not just who gets to talk, but what they research; cross-cultural differences; the growing role of geographic and temporal distance issues; suspicion of the actual value of law and ethics in a harsh realm like war; and a growing suspicion of science itself. If we hope better to address our growing ethical concerns, we must face up to these underlying issues as well. (shrink)

History of Science is a many-sided subject, permitting approach from the point of view of various human interests, and presenting a wide variety of problems, many of them paradoxical and perhaps not capable of satisfactory solution. In the following it will probably seem to the reader a number of times that I am talking at cross purposes. Anything that I can say is of necessity limited by my background as a physicist.

Consciousness has long been a subject of interest in philosophy and religion but only relatively recently has it become subject to scientific investigation. Now, more than ever before, we are beginning to understand this mental state. Developmental psychologists understand when we first develop a sense of self; neuropsychologists see which parts of the brain activate when we think about ourselves and which parts of the brain control that awareness. Cognitive scientists have mapped the circuitry that allows machines to have some (...) form of self awareness, and neuroscientists investigate similar. (shrink)

Pekakak adalah salah satu tokoh yang memiliki pengetahuan mendalam dan perencanaan yang cermat. Saat fajar menyingsing, ia terlihat bertengger di atas pohon. Dengan kemampuan sempurna untuk mengontrol kecepatan penerbangan miliknya, seperti kapan harus memperlambat atau mempercepat, dia dapat dengan mudah menghitung cara optimal untuk menangkap ikan.