We developed an ex silico evolutionary‐based systematic synteny approach to define and name the duplicated genes in vertebrates. The first convention for the naming of genes relied on historical precedent, the order in the human genome, and mutant phenotypes in model systems. However, total‐genome duplication that resulted in teleost genomes required the naming of duplicated orthologous genes (ohnologs) in a specific manner. Unfortunately, as we review here, such naming has no defined criteria, and some ohnologs and their orthologs have suffered (...) from incorrect nomenclature, thus creating confusion in comparative genetics and disease modeling. We sought to overcome this barrier by establishing an ex silico evolutionary‐based systematic approach to naming ohnologs in teleosts. We developed software and compared gene synteny in zebrafish using the spotted gar genome as a reference, representing the unduplicated ancestral state. Using new criteria, we identified several hundred potentially misnamed ohnologs and validated the principle manually. Also see the video abstract here: https://youtu.be/UKNLa_TvSgY. (shrink)

Informed consent is one of the most important ethical and legal principles in the United States, including Texas, and reflects a profound respect for individuals and their ability to make decisions in their own best interest. It is also a critical underpinning of medical practice, although how it is actually carried out has not been well studied. A survey was conducted in the private practices and a hospital in the Texas Medical Center in Houston, Texas to ascertain how physicians, patients (...) and patient's family members perceive and demonstrate the elements of informed consent. In-depth interviews of twelve physicians, three patients and three family members were carried out. For physicians, consent was an explicit and implicit aspect of virtually all medical practice. Physicians would seek patient input concerning medical decisions whenever possible and might also discuss care choices with families. However, they often made decisions based upon what they perceived as the patient's best interests. Patients expected the physician to involve them in the decision process, but whether they turned to family members, or even others to assist them, varied considerably. Although Texas physicians respect the competent patient as the primary decision maker, they may bypass a formal surrogate decision maker to gain input from others, including their own view of what is in the patient's best interest. (shrink)

Houston, Texas, is a major U.S. city with, like many, a growing aging population. The purpose of this study and ultimate book chapter is to explore the views and perceptions of long-term care (LTC) residents, family members and health care providers. Individuals primarily in independent living and group residential settings were interviewed and studied. Questions emphasized the concepts of personal autonomy, dignity, quality and location of care and decision making. Although a small sample of participants were involved, consistency was noted. (...) Keeping the elderly in caring and loving home situations (theirs or family) was most preferred. Personal choice and independence were emphasized by residents, but family members needed to act as advocates. We also noted that the legal system emphasizes family control over individual decision making as competency declines with aging. Optimal personal decision making in the residents' best interest also became more difficult with loss of individual mental capacity. (shrink)

The aim of this paper has been to draw attention to the non-cognitive aspects of Vygotsky's theoretical heritage. We hope that we have succeeded in presenting here his principal ideas on motivation and volition in the present-day problem context. It should be noted that the problem of human freedom and self-determination was of great importance for Vygotsky, though the explicit discussion of this problem is not common in his writings. Approaching this problem both as a philosopher and as a psychologist, (...) Vygotsky inevitably had first to get some idea of the general psychological regularities which could serve as a concrete-psychological basis for the constructive paradigm in the explanation of the phenomena of human freedom and “non-freedom.” It is highly probable that he planned to discuss this problem at length in his last uncompleted book,Doctrine of Affects. However, even the existing texts provide a weighty and insightful basis not only for scientific research but also for creating applied methods of enhancement of human will-power, or, more exactly, the talent to will. Some of the possibilities, revealed by the Vygotskian approach, are presented in the last section. Many other of Vygotsky's brilliant ideas still await an unbiased reading in the contemporary, rather than merely historical, context. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (shrink)

Sildenafil citrate (Viagra) and other newly released pharmaceuticals that assist erectile dysfunction may be one of the most important categories of drugs released in the past decade. Sildenafil is distinctive because it creates a new therapeutic relationship not only between patient and physician, but also with sexual partner(s). Physicians must first evaluate the patient comprehensively, addressing not only erectile function and sexual performance, but overall physical and mental health. Since the drug does impact others, an expanded model for informed consent (...) needs to be considered. Three models to consider include the public health one, ethically justified limits on confidentiality, and a biopsychosocial one. The biopsychosocial model may be preferred because it expands the patient-physician dyad to directly include others. Physicians also need to distinguish between professional, role-related obligations and personal conscience when treating patients whose sexual beliefs and practices differ from their own. Other ethical issues include inappropriate prescribing over the Internet, dealing with unrealistic patient expectations, and fairness in paying for treatment for sexual conditions in both men and women. With these proposed guidelines, physicians can continue to provide steady, reliable guidance for patients while working with yet another scientific advance in medicine. (shrink)

Host‐pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti‐pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is “deemed” capable (...) of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins‐antitoxins, suggestive of immunity‐PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR‐Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD. (shrink)

A simple quantum relativistic model of ν µ − ντ neutrino oscillations in the OPERA experiment is presented. This model suggests that the two components in the neutrino beam are separated in space. After being created in a meson decay, the µ-neutrino moves 18 meters ahead of the beam’s center of energy, while the τ -neutrino is behind. Both neutrinos have subluminal speeds, however the advanced start of the ν µ explains why it arrives in the detector 60 ns earlier (...) than expected. Our model does violate the special-relativistic ban on superluminal signals. However, usual arguments about violation of causality are not applicable here. The invalidity of standard special-relativistic arguments is related to the interaction-dependence of the boost operator, which implies that boost-transformed space-time coordinates of events with interacting particles do not obey linear and universal Lorentz formulas. (shrink)

In quantum relativistic Hamiltonian dynamics, the time evolution of interacting particles is described by the Hamiltonian with an interaction-dependent term (potential energy). Boost operators are responsible for (Lorentz) transformations of observables between different moving inertial frames of reference. Relativistic invariance requires that interaction-dependent terms (potential boosts) are present also in the boost operators and therefore Lorentz transformations depend on the interaction acting in the system. This fact is ignored in special relativity, which postulates the universality of Lorentz transformations and their (...) independence of interactions. Taking into account potential boosts in Lorentz transformations allows us to resolve the “no-interaction” paradox formulated by Currie, Jordan, and Sudarshan [Rev. Mod. Phys. 35, 350 (1963)] and to predict a number of potentially observable effects contradicting special relativity. In particular, we demonstrate that the longitudinal electric field (Coulomb potential) of a moving charge propagates instantaneously. We show that this effect as well as superluminal spreading of localized particle states is in full agreement with causality in all inertial frames of reference. Formulas relating time and position of events in interacting systems reduce to the usual Lorentz transformations only in the classical limit (ħ→0) and for weak interactions. Therefore, the concept of Minkowski space-time is just an approximation which should be avoided in rigorous theoretical constructions. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (shrink)

A recent analysis of genome‐wide expression patterns and regulatory motif content of paralogous yeast genes1 strongly suggests that mutational robustness (backup) between paralogous genes is achieved via transcriptional reprogramming of one paralog to compensate for the loss or silencing of the other. BioEssays 27:865–868, 2005. Published 2005 Wiley Periodicals, Inc.

Rarely do Introduction to Philosophy textbooks connect, in any thoroughgoing way, the study of philosophy with examples from literature. While contemporary analytic thinkers often tie literary works to philosophical themes and some serious philosophers have written works of literature, these two ways of linking literature to philosophy face significant pedagogical disadvantages. Another tack is to choose a literary work written by a novelist that has implications for philosophical subjects. This paper describes just such a strategy, namely by supplementing traditional materials (...) for an Introduction to Philosophy course with Daniel Trumbo’s “Johnny Got His Gun.”. (shrink)

This paper explores the connection between supererogation and the integrity of ethical agents. It argues two theses: there is a generally unrecognized but crucial social dimension to the moral integrity of individuals which challenges individual ideals and encourages supererogation; the social dimension of integrity, however, must have limits that preserve the individuals's integrity. The concept of integrity is explored through recent works by Christine Korsgaard, Charles Taylor, and Susan Babbitt. A life of integrity is in part a life whereby one (...) 'lives up to' one's own deeply held values. Yet, as one seeks to transcend the realm of the morally customary or the dutiful, one must check one's progress not only against one's own ideals but against the ideals and behavior of the ethical community. To answer affirmatively to one's own ideals is to hear the call of integrity both from within oneself and from without. However, by being free to hear, the freedom to close one's ears inevitably will arise. Only actions displaying such freedom can be actions of moral integrity. Since supererogatory actions are always left to an agent's discretion-that is, are fully optional-they show in paradigmatic fashion the integrity of moral agents. While an ethic of integrity and supererogation provides challenges to members of an ethical community by encouraging them continually to reevaluate their actions and character in reference to postulated ideals, it also leads us to be quite wary of judging individual's moral motives from the outside. A passage by Jonathan Kozol is cited that suggests our society routinely demands supererogatory action from its poorest members. This is illegitimate since they live in conditions that alienate rather than integrate them both with themselves and with the rest of the community. (shrink)

Exploration of immune systems in prokaryotes, such as restriction‐modification or CRISPR‐Cas, shows that both innate and adaptive systems possess programmed cell death (PCD) potential. The key outstanding question is how the immune systems sense and “predict” infection outcomes to “decide” whether to fight the pathogen or induce PCD. There is a striking parallel between this life‐or‐death decision faced by the cell and the decision by temperate viruses to protect or kill their hosts, epitomized by the lysis‐lysogeny switch of bacteriophage Lambda. (...) Immune systems and temperate phages sense the same molecular inputs, primarily, DNA damage, that determine whether the cell lives or dies. Because temperate (pro)phages are themselves components of prokaryotic genomes, their shared “interests” with the hosts result in coregulation of the lysis‐lysogeny switch and immune systems that jointly provide the cell with the decision machinery to probe and predict infection outcomes, answering the life‐or‐death question. (shrink)

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron‐rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution (...) are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification. (shrink)

Eukaryotic gene expression is extensively controlled at the level of mRNA stability and the mechanisms underlying this regulation are markedly different from their archaeal and bacterial counterparts. We propose that two such mechanisms, nonsense‐mediated decay (NMD) and motif‐specific transcript destabilization by CCCH‐type zinc finger RNA‐binding proteins, originated as a part of cellular defense against RNA pathogens. These branches of the mRNA turnover pathway might have been used by primeval eukaryotes alongside RNA interference to distinguish their own messages from those of (...) RNA viruses and retrotransposable elements. We further hypothesize that the subsequent advent of “professional” innate and adaptive immunity systems allowed NMD and the motif‐triggered mechanisms to be efficiently repurposed for regulation of endogenous cellular transcripts. This scenario explains the rapid emergence of archetypical mRNA destabilization pathways in eukaryotes and argues that other aspects of post‐transcriptional gene regulation in this lineage might have been derived through a similar exaptation route. -/- . (shrink)

Rarely do Introduction to Philosophy textbooks connect, in any thoroughgoing way, the study of philosophy with examples from literature. While contemporary analytic thinkers often tie literary works to philosophical themes and some serious philosophers have written works of literature, these two ways of linking literature to philosophy face significant pedagogical disadvantages. Another tack is to choose a literary work written by a novelist that has implications for philosophical subjects. This paper describes just such a strategy, namely by supplementing traditional materials (...) for an Introduction to Philosophy course with Daniel Trumbo’s “Johnny Got His Gun.”. (shrink)

Scale-free network models describe many natural and social phenomena. In particular, networks of interacting components of a living cell were shown to possess scale-free properties. A recent study(1) compares the system-level properties of metabolic and information networks in 43 archaeal, bacterial and eukaryal species and claims that the scale-free organization of these networks is more conserved during evolution than their content. BioEssays 24:105–109, 2002. Published 2002 Wiley Periodicals, Inc.

Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla, sometimes grouped together as the PVC superphylum of eubacteria. Some PVC species possess interesting attributes, in particular, internal membranes that superficially resemble eukaryotic endomembranes. Some biologists now claim that PVC bacteria are nucleus‐bearing prokaryotes and are considered evolutionary intermediates in the transition from prokaryote to eukaryote. PVC prokaryotes do not possess a nucleus and are not intermediates in the prokaryote‐to‐eukaryote transition. Here we summarise the evidence that shows why all of the PVC traits (...) that are currently cited as evidence for aspiring eukaryoticity are either analogous (the result of convergent evolution), not homologous, to eukaryotic traits; or else they are the result of horizontal gene transfers. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Narrative SymposiumPersonal Narratives Experiences of Psychiatric HospitalizationV. Barnard, J. Carson, Eugene Doe, Robin Driben, Anonymous One, Anonymous Two, Charles Kelley, Michael Kerins, D. Millman, Anonymous Three, Viesia Novosielski, Ben Zion, and Anonymous Four• Dreaming: A Recovery Story• The Intervention of the Demon• Bent but Not Broken• Tortured Souls Do Not Rest• Homesick• A Professional Patient No More• My Spiritual Journey• Personal Account of Psychiatric Hospitalization• Psychiatric Hospitalization Story• (...) As Ice Is to Water• The Power Of Human-To-Human Contact• Dignity• HospitalizationCopyright © 2011 The Johns Hopkins University Press... (shrink)

This crucial volume contains a newly-edited cache of over thirty essays on a diverse range of topics from the renowned philosopher, Adam Ferguson, a leading figure of the Scottish Enlightenment. Following on from The Correspondence of Adam Ferguson, this collection aims to set the essays more fully in the history of western philosophy, to which they made an important contribution. They give an exhaustive picture of the thinking of the author and expound ideas which build on and extend the originality (...) of his earlier work. The need for systematic writing in his earlier, published work inevitably marginalized the topics of interest that Ferguson would resume in the leisure of his retirement, when he was free to rethink and clarify earlier problems. Long-unpulished, his later essays represent a re-appraisal of the philosophical, historical and anthropoligical themes that he had examined before. In this authoritative edition, Ferguson's views on disparate philosophical, anthropological and historical topics can at last be viewed in one impressive volume. His texts are transcribed as faithfully as possible and are accompanied by extensive introductions from the general editor and both contributing editors. (shrink)

The morbidity of tick‐borne encephalitis (TBE) varies yearly by as much as 10‐fold among the people of Western Siberia. This long‐term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub‐adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non‐viremic horizontal transmission, we emphasize the recently (...) understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus‐host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks. (shrink)

The aim of the paper is to examine various aspects of holism, especially with regard to scientific knowledge and scientific realism. It is concerned with that tradition of holism, which has been largely influenced by W. V. O. Quine, but in some respects also by T. S. Kuhn. It offers a survey of different versions of holism , evaluating at the same time various aspects of the holistic approach. Attention is paid also to anti-holistic critique ant its contribution to understanding (...) the nature and development of scientific knowledge. (shrink)

Content: Sprache, Recht und Rechtsverbindlichkeit: R. Fukawa: An Analysis of the aeRules of Recognition Statement' u W. Krawietz: What does it mean to follow an aeInstitutionalised Legal Rule'? u N. MacCormick: Citizens' Legal Reasoning and its Importance for Jurisprudence u Y. Morigiwa: Hart's Theories of Language and Law u R.Tuomela: Supervenience, Collective Action, and Kelsen's Organ Theory uRecht und politische Kultur: G. Haney: Recht als Form von Kultur u A. Kojder: Dysfunctionalities of Legal Cultur u A. Lopatka: Law and Religion (...) in Poland u M. Samu: Culture and Law: Legal Culture uWerteordnung als ideologische Basis des Rechtsstaats: R. Dreier: Konstitutionalismus und Legalismus u O. Maenpaa: Unilaterality and Consensualism in the Application of Law u K.-F. Lenz: Zivilprozea und Spiel u M. Pavcnik: Ideologie der Rechtsanwendung versus argumentierte Rechtsentscheidung u J. Uusitalo: Legal Dogmatics, Epistemology, Radical Hermeneutics u Entwicklung der Rechtsordnung und soziale Gerechtigkeit: V. Luizzi: Legal Validity and Justice u H. Rottleuthner: Recht und Technik in entwicklungstheor. Perspektive u S. Panou: Uber die aeGerechtigkeit' des Rechts u A. Squella: Legal Positivism and Democracy in the 20. Century u D. Wyduckel: Konsens und gesellschaftlich-technischer Fortschritt u Soziale Mechanismen der Rechtsanwendung und Rechtsfindung: H. Aoi: Richterliche Rechtsfindung als Pattern-Matching-Prozea uu.a. (Franz Steiner 1991). (shrink)

Gegenstand der Nikomachischen Ethik (ca. 335-323 v. Chr.) ist das >tätige Leben.

1) vgl.,,50phistes" 248c4 - 253c3 und 254b7-257aI2. 2) Heidegger, Brief über den "Humanismus"; s. in "Platons Lehre von der Wahrheit", Bern 1947,5.53. 3) 5. Diels "Fragmente der Vorsokratiker"6, Berlin 1951; Parmenides B l. 4) Reinhardt "Parmenides und die Geschichte der griechischen Philosophie", Bonn 1916, 5.32 ff.; zu dem Verhältnis der beiden "Teile" des Gedichts ist u.a. zu vergleichen: Fränkel "Parmenidesstudien" (Götting. Nachr. 1930, 5.153 ff.), Abschnitt IV und V; Calogero, 5tudi sull' Eleatismo, Rom 1932; Riezler "Par­ menides", Frankfurt 1934 (dazu (...) die Rezension von Gadamer in "Gnomon" XII 1936,5.77 ff.); Jaeger "Die Theologie der frühen griechischen Denker", 5tutt­ gart 1953,5.123 f.. 5) B 8,1 '"!J.6~o~ i3't;,~ t-'"ü'&?~ o~?,Io AeL7tE'Tct,L w~, e,O'''n~.. ~., 6) B 8,2... "t"lXu··nJI Il zm. (shrink)

'Implicit understanding' is much wider than what we can attend to at one time, and it is in some respects more precise. Examples are examined. What is implicit functions in certain characteristic ways. Some of these are defined. They explain how new concepts come to us in a bodily process that goes beyond previous logic but takes implicit account of it, without new logical steps. All concepts can be considered 'explications' of implicit body- environment interaction. 'Explication' provides an overall model (...) within which the objectivity of logical concepts can be explained and preserved. Section III concerns new kinds of operational research. Section IV shows how a theory of logically connected terms can always be formulated from something known implicitly. Section V shows how the explication model affects the theory of language. (shrink)