Recent evidence indicates that transcriptional bursts are intrinsically amplified by messenger RNA cytoplasmic processing to generate large stochastic fluctuations in protein levels. These fluctuations can be exploited by cells to enable probabilistic bet‐hedging decisions. But large fluctuations in gene expression can also destabilize cell‐fate commitment. Thus, it is unclear if cells temporally switch from high to low noise, and what mechanisms enable this switch. Here, the discovery of a post‐transcriptional mechanism that attenuates noise in HIV is reviewed. Early in its (...) life cycle, HIV amplifies transcriptional fluctuations to probabilistically select alternate fates, whereas at late times, HIV utilizes a post‐transcriptional feedback mechanism to commit to a specific fate. Reanalyzing various reported post‐transcriptional negative feedback architectures reveals that they attenuate noise more efficiently than classic transcriptional autorepression, leading to the derivation of an assay to detect post‐transcriptional motifs. It is hypothesized that coupling transcriptional and post‐transcriptional autoregulation enables efficient temporal noise control to benefit developmental bet‐hedging decisions. (shrink)

Co‐expression of two or more genes at the single‐cell level is usually associated with functional co‐regulation. While mRNA co‐expression—measured as the correlation in mRNA levels—can be influenced by both transcriptional and post‐transcriptional events, transcriptional regulation is typically considered dominant. We review and connect the literature describing transcriptional and post‐transcriptional regulation of co‐expression. To enhance our understanding, we integrate four datasets spanning single‐cell gene expression data, single‐cell promoter activity data and individual transcript half‐lives. Confirming expectations, we find that positive co‐expression necessitates (...) promoter coordination and similar mRNA half‐lives. Surprisingly, negative co‐expression is favored by differences in mRNA half‐lives, contrary to initial predictions from stochastic simulations. Notably, this association manifests specifically within clusters of genes. We further observe a striking compensation between promoter coordination and mRNA half‐lives, which additional stochastic simulations suggest might give rise to the observed co‐expression patterns. These findings raise intriguing questions about the functional advantages conferred by this compensation between distal kinetic steps. (shrink)

Background One of the objectives of medicine is to relieve patients' suffering. As a consequence, it is important to understand patients' perspectives of suffering and their ability to cope. However, there is poor insight into what determines their suffering and their ability to bear it. Purpose To explore the constituent elements of suffering of patients who explicitly request euthanasia or physician-assisted suicide (EAS) and to better understand unbearable suffering from the patients' perspective. Patients and methods A qualitative study using in-depth (...) face-to-face interviews was conducted with 31 patients who had requested EAS. The grounded theory approach was used to analyse the data. Results Medical, psycho-emotional, socio-environmental and existential themes contributed to suffering. Especially fatigue, pain, decline, negative feelings, loss of self, fear of future suffering, dependency, loss of autonomy, being worn out, being a burden, loneliness, loss of all that makes life worth living, hopelessness, pointlessness and being tired of living were constituent elements of unbearable suffering. Only patients with a psychiatric (co)diagnosis suffered unbearably all the time. Conclusions Unbearable suffering is the outcome of an intensive process that originates in the symptoms of illness and/or ageing. According to patients, hopelessness is an essential element of unbearable suffering. Medical and social elements may cause suffering, but especially when accompanied by psycho-emotional and existential problems suffering will become ‘unbearable’. Personality characteristics and biographical aspects greatly influence the burden of suffering. Unbearable suffering can only be understood in the continuum of the patients' perspectives of the past, the present and expectations of the future. (shrink)

Non-fiction graphic novels about illness and death created by patients and their loved ones have much to teach all readers. However, the bond of empathy made possible in the comic form may have special lessons for healthcare providers who read these texts and are open to the insights they provide.

In aging humans, aerobic exercise interventions have been found to be associated with more positive or less negative changes in frontal and temporal brain areas, such as the anterior cingulate cortex (ACC) and hippocampus, relative to no-exercise control conditions. However, individual measures such as gray-matter (GM) probability may afford less reliable and valid conclusions about maintenance or losses in structural brain integrity than a latent construct based on multiple indicators. Here, we established a latent factor of GM structural integrity based (...) on GM probability assessed by voxel-based morphometry, magnetization transfer saturation, and mean diffusivity. Based on this latent factor, we investigated changes in structural brain integrity during a six-month exercise intervention in brain regions previously reported in studies using volumetric approaches. Seventy-five healthy, previously sedentary older adults aged 63–76 years completed an at-home intervention study in either an exercise group (EG;n= 40) or in an active control group (ACG;n= 35). Measures of peak oxygen uptake (VO2peak) taken before and after the intervention revealed a time-by-group interaction, with positive average change in the EG and no reliable mean change in the ACG. Significant group differences in structural brain integrity changes were observed in the right and left ACC, right posterior cingulate cortex (PCC), and left juxtapositional lobule cortex (JLC). In all instances, average changes in the EG did not differ reliably from zero, whereas average changes in the ACG were negative, pointing to maintenance of structural brain integrity in the EG, and to losses in the ACG. Significant individual differences in change were observed for right ACC and left JLC. Following up on these differences, we found that exercising participants with greater fitness gains also showed more positive changes in structural integrity. We discuss the benefits and limitations of a latent-factor approach to changes in structural brain integrity, and conclude that aerobic fitness interventions are likely to contribute to brain maintenance in old age. (shrink)

There is no doubt that custard apple diseases are among the important reasons that destroy the Custard Apple plant and its agricultural crops. This leads to obvious damage to these plants and they become inedible. Discovering these diseases is a good step to provide the appropriate and correct treatment. Determining the treatment with high accuracy depends on the method used to correctly diagnose the disease, expert systems can greatly help in avoiding damage to these plants. The expert system correctly diagnoses (...) Custard Apple disease to make it easier for farmers to find the right treatment based on the appropriate diagnosis. Objectives: A specialized syllable language system was established for the diagnosis of Custard Apple plant disease. (shrink)

The notion of a Sasaki projectionon an orthomodular lattice is generalized to a mapping Φ: E × E → E, where E is an effect algebra. If E is lattice ordered and Φ is symmetric, then E is called a Φ-symmetric effect algebra.This paper launches a study of such effect algebras. In particular, it is shown that every interval effect algebra with a lattice-ordered ambient group is Φ-symmetric, and its group is the one constructed by Ravindran in his proof that (...) every effect algebra that has the Riesz decomposition property is an interval algebra. It is shown that the doubling construction introduced in the paper is connected to the conditional event algebrasof Goodman, Nguyen, and Walker. (shrink)

Background: Hospital nurses are frequently the first care givers to receive a patient’s request for euthanasia or physician-assisted suicide (PAS). In France, there is no consensus over which medical practices should be considered euthanasia, and this lack of consensus blurred the debate about euthanasia and PAS legalisation. This study aimed to investigate French hospital nurses’ opinions towards both legalisations, including personal conceptions of euthanasia and working conditions and organisation. Methods: A phone survey conducted among a random national sample of 1502 (...) French hospital nurses. We studied factors associated with opinions towards euthanasia and PAS, including contextual factors related to hospital units with random-effects logistic models. Results: Overall, 48% of nurses supported legalisation of euthanasia and 29%, of PAS. Religiosity, training in pallative care/pain management and feeling competent in end-of-life care were negatively correlated with support for legalisation of both euthanasia and PAS, while nurses working at night were more prone to support legalisation of both. The support for legalisation of euthanasia and PAS was also weaker in pain treatment/palliative care and intensive care units, and it was stronger in units not benefiting from interventions of charity/religious workers and in units with more nurses. Conclusions: Many French hospital nurses uphold the legalisation of euthanasia and PAS, but these nurses may be the least likely to perform what proponents of legalisation call “good” euthanasia. Improving professional knowledge of palliative care could improve the management of end-of-life situations and help to clarify the debate over euthanasia. (shrink)

The article examines the genre specificity of Friedrich Hebbel’s dramaturgy. The attention is drawn to the operation of various genre elements in his works. The basic principles of creation of philosophical and mythological tragedy by Friedrich Hebbel are analyzed. The gnoseological conception of cognition of the world which relies on the ontological structure, transferring the center of gravity of the drama to the idea development, extension of space and time at the expense of inserting mythological plot and symbolism as the (...) signs of the genre. The philosophical and mythological tragedy of Friedrich Hebbel makes sense of ontological categories, elaborates ideas of social philosophy and philosophy of history. (shrink)

Using the mathematical notion of an entity to represent states in quantum and classical mechanics, we show that, in a strict sense, proper superpositions are possible in classical mechanics.

Hegel raises many real problems on the basis of the phenomenology of spirit: logico-ontological, gnoseological, and philosophico-historical problems. But in all spheres, levels, and forms of consciousness, Hegel investigates particularly the formation of the socially developed and historically oriented universal subject of thought, will, and action in the context of the forms of the manifest spirit, forms that in reality assume the status of being. It is precisely this investigation that constitutes the real problematic of Hegel's Phenomenology of Spirit.

This Is A New Release Of The Original 1920 Edition.

Judgment aggregation theory, which concerns the translation of individual judgments on logical propositions into consistent group judgments, has shown that group consistency generally cannot be guaranteed if each proposition is treated independently from the others. Developing the right method of abandoning independence is thus a high-priority goal. However, little work has been done in this area outside of a few simple approaches. To fill the gap, we compare four methods based on distance metrics between judgment sets. The methods generalize the (...) premise-based and sequential priority approaches to judgment aggregation, as well as distance-based preference aggregation. They each guarantee group consistency and implement a range of distinct functions with different properties, broadening the available tools for social choice. A central result is that only one of these methods (not previously considered in the literature) satisfies three attractive properties for all reasonable metrics. (shrink)

Are values and social priorities universal, or do they vary across geography, culture, and time? This question is very relevant to Asia’s emerging economies that are increasingly looking at Western models for answers to their own outmoded health care systems that are in dire need of reform. But is it safe for them to do so without sufficient regard to their own social, political, and philosophical moorings? This article argues that historical and cultural legacies influence prevailing social values with regard (...) to health care financing and resource allocation, and that the Confucian dimension provides a helpful entry point for a deeper understanding of ongoing health care reforms in East Asia – as exemplified by the unique case of Singapore. (shrink)

Merab Konstantinovich [Mamardashvili] met with me immediately, as soon as I requested it, although he forewarned me that he could only dimly remember much of that distant past in which I was most interested. But evidently that past still perturbed him as well, since he agreed to speak with me even though he had not yet completely recovered from his illness, and hence his voice was feeble, at times subsiding to a whisper; he would pronounce his words indistinctly, constantly sticking (...) one onto another; on top of that, for technical reasons the dictaphone was situated a bit away from him. It was therefore very difficult to transcribe the text, and I raised many questions with the idea of asking Merab Konstantinovich about them at our next meeting and clearing up some things. But alas, there was no next meeting … Hence I am permitting myself now to publish only some of the most clearly enunciated fragments of my conversation with him, one of the four "forefathers" of the Moscow Methodological Circle, whose name for us, today's participants (and hence neophytes) in the methodological movement, is enveloped by legends handed down by word of mouth. I kept my questions to a minimum. Mamardashvili's reminiscences, arguments, and reflections will seem contentious to many. But no matter, one can dispute points of substance even with those who have passed on. (shrink)

This 1990 collection explores one recurrent theme connecting philosophy and politics: the relation between the nature of man and the structure of society. It does so by concentrating on the topical issue of the market economy as an attempt to resolve the clash between individual autonomy and collective action. Beginning with a historical and personal recollection by Enoch Powell and a response by Robert Skidelsky, the volume then provides a forum for political theorists and philosophers to take issue on the (...) fundamental topics of markets and morals; liberal man; and equality and libertarianism. It succeeds equally as a stimulating textbook and a book for the general reader who wishes to understand the philosophical issues arising in a market economy. (shrink)

In Prior’s [4], Appendix A §4 and §5, and Chapter IV, and more explicitly in Bull’s [2], we find sequences of tense-logical systems which place increasingly more restrictive conditions on the temporal relation “… is before …”. We give here a simple, diagrammatic account of the way in which the successive postulates for temporal order place these conditions on the temporal relation: we do not provide any essentially new semantics for these systems, nor do we prove any rigorous metatheorems. We (...) do, however, quite often assume the completeness results of Lemmon, Bull and others without explicit mention. (shrink)