The degradation of the majority of cellular proteins is mediated by the proteasomes. Ubiquitin‐dependent proteasomal protein degradation is executed by a number of enzymes that interact to modify the substrates prior to their engagement with the 26S proteasomes. Alternatively, certain proteins are inherently unstable and undergo “default” degradation by the 20S proteasomes. Puzzlingly, proteins are by large subjected to both degradation pathways. Proteins with unstructured regions have been found to be substrates of the 20S proteasomes in vitro and, therefore, unstructured (...) regions may serve as signals for protein degradation “by default” in the cell. The literature is loaded with examples where engagement of a protein into larger complexes increases protein stability, possibly by escaping degradation “by default”. Our model suggests that formation of protein complexes masks the unstructured regions, making them inaccessible to the 20S proteasomes. This model not only provides molecular explanations for a recent theoretical “cooperative stability” principle, but also provokes new predictions and explanations in the field of protein regulation and functionality. BioEssays 28: 844–849, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:French Philosophical Thought: Present Trends of French Philosophical Thought *Alexandre Koyré*This is a rather large subject, so you will not be astonished that I shall not treat it in its entirety. French philosophy during the years of war and occupation was pretty active. Though there were some heavy losses: the death of Brunschvicg, posthumous book [...], Héritage de mots, héritage d’idées, 1 a book written when Brunschvicg was in (...) hiding, and a book as “clear and serene as that of Condorcet,” has appeared after the liberation of France; the death of Halbwachs, of Politzer, of Cavaillès, of Lautman shot by the Nazis, of others less well known...; there was the ban on publications by Jewish authors, yet, in spite of this, there has been a surprising number of interesting and even important publications, both during and after the war.It seems that for the elder generation of French philosophers—and that applies not only to philosophers, but to scholars in general—for the generation of men too old to take an active part in the underground move-ment—work, as if nothing happened, has been in the same time a means of escape and a means of resistance. They felt themselves asserting a spiritual tradition that could not be destroyed, and should not be destroyed, and should not be endangered by such contingent “accidents” as Vichy government or even the Gestapo.Thus there have been a new translation of Plato by Robin, books on Plato, on Aristotle, on the medieval (Gilson) and modern philosophy etc., books on philosophy of science, books on sociology, psychology, logic (Méray, Serrus), 2 philosophy of religion, translations of philosophy classics. At the first glance the bibliography of this period (Lavelle, Le Senne, Bachelard, Gilson, etc.) you could have the impression wander in a familiar landscape: yet this would be a completely false impression, because as a matter of fact, this familiar landscape has been completely upturned by the upsurge of existentialism and the revival of Catholic philosophy [End Page 531] (Fessard, 3 De Lubac, Blondel, Nedoncelle, G. Marcel). Under this double impact everything—even the “climate” of philosophy—has changed. Philosophy has become a socially phenomenon.Neither Catholicism nor existentialism are, of course, specifically French intellectual movements. Catholicism is universal ex definitione, and as for existentialism, though French existentialism possesses some specific fea-tures that distinguish it from and even oppose it to the German one, fea-tures that can probably be explained by different national traditions—Descartes, Pascal—it, too, is no more French than it is German. Existen-tialism as such is European by-phenomenon, a definite phase of Western philosophical thought (and European thought, European civilization, at least until the recent—perhaps successful—attempts to destroy it, has been a unity). It originates more than a hundred years ago with Maine de Biran and Kierkegaard, and only has been rediscovered by the twentieth century now. Two thinkers that have been nearly completely neglected by the 19th century—but the 19th century, at least the second part of it, has been a dark age for philosophy—and after the rediscovery or simply the discovery of Kierkegaard in the 20th, it spreads, in Kierkegaard’s wake, from country to country with the usual speed or delay with which ideas travel today. Thus existential philosophy has been, first, developed in Germany in the ‘20s and ‘30s by Heidegger and Jaspers, then—Kierkegaard having been translated into French during the long armistice between the World Wars—in France, some 15 years later. 4 I have heard, by the way, that Kierkegaard has been, or is in the process of being translated into English. So, it is possible that in some 15 or 20 years you will have an existentialism in this country.But to return to France, the rise or upsurge of existentialism has been extraordinarily rapid. It was simultaneous with Husserl’s phenomenolo-gy becoming known in France (Husserl’s last work, Meditations Car-tesiennes, being the text of the lectures he gave in the Sorbonne in 1929, which is now available only in the French translation): from Husserl to... (shrink)

Background: Depression (major depressive disorder) is a common and serious medical illness that negatively affects how you feel, the way you think and how you act. Fortunately, it is also treatable. Depression causes feelings of sadness and/or a loss of interest in activities once enjoyed. It can lead to a variety of emotional and physical problems and can decrease a person’s ability to function at work and at home. Depression affects an estimated one in 15 adults (6.7%) in any given (...) year. And one in six people (16.6%) will experience depression at some time in their life. Depression can strike at any time, but on average, first appears during the late teens to mid-20s. Women are more likely than men to experience depression. Some studies show that one-third of women will experience a major depressive episode in their lifetime. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment and give the appropriate method of treatment through several tips that concern the disease and how to treat it and we will see it through the application on the expert system. Methods: in this paper the design of the proposed Expert System which was produced to help Psychologist in diagnosing depression disease through its symptoms such as: a loss of energy, a change in appetite, sleeping more or less, anxiety, reduced concentration, indecisiveness, restlessness, feelings of worthlessness, guilt or hopelessness and thoughts of self-harm or suicide. The proposed expert system presents an overview about depression disease is given, the cause of diseases is outlined and the treatment of disease whenever possible is given out. SL5 Object Expert System language was used for designing and implementing the proposed expert system. Results: The proposed depression disease diagnosis expert system was evaluated by psychologist students and they were satisfied with its performance. Conclusions: The Proposed expert system is very useful for psychologist, patients with depression and newly graduated psychologist. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Truth in WritingAmandaAn excerpt from my journal during a dark period in my life reads:I am a survivor of sexual mutilation, of coerced gender roles, and of perpetual lies all in the name of normalization. Sometimes I have a hard time even thinking about the true extent of what all happened. It’s like my mind doesn’t have that type of scope, like when I think about the word (...) “eternity.”I wrote this after combing through old medical records, reading comments like “her introitus has healed nicely and looks normal, but my exam suggests that her vagina is shortened,” and “reduction clitoroplasty... removal of testes.” The records go on to say that my “external genitalia is quite satisfactory,” and “on perineal exam, her neovaginal orifice is quite compliant and easily accepts my second and third digits.”My journal continues:I chose this fake hole when I was a teenager because I didn’t know there was another option. I was told from day one to be a female, to be heteronormative, to act like all the other girls, and the only way I could fully accomplish this is by looking the part. A fake hole would be necessary, I thought, to go along with the rest of the lies. Sometimes I think about how the doctors told me to lie about my surgeries and my scars. Sometimes I wonder what my parents would have told the world if I had died during one of surgeries. Maybe they would have said “we were just trying to make her fuckable.”My strength is growing from the stories and experiences I write and share. My journal started about four years ago, when I was in my early 20s, near the beginning of medical school. My initial purpose in writing the journal was to help sort through my feelings and experiences related to a newly discovered sexuality and a changing gender identity. Medical school was thousands of miles away from my previous life, my family, and my friends. Away from my old social network, I was free to self–discover on my own terms. In the first journal entry, I lay out reasons why I decided to get in contact with a therapist, something I had not done previously. Some of the reasons were fairly standard reasons one seeks out a therapist, such as moving away from home. But the fundamental reasons I sought out a therapist, and why I chose to journal, had to do with exploring feelings after my first sexual encounter with a woman, and then [End Page 98] accepting my intersexuality. My relationship with that therapist did not last, but the journaling did.In the beginning of the journal, I write:I am from a small, religious, white, non–diverse, family oriented suburb of Milwaukee. I was raised to be the picture–perfect daughter in a household that did not talk about feelings, sex, cultural or religious differences, etc. My brother and I also never talked about personal issues (and still don’t), which is quite remarkable since we are twins, and have grown up doing most everything together, from sharing birthday parties, to being locker buddies... [When my mother told me about having Androgen Insensitivity Syndrome (AIS)] knowing this little fact about my body kept me wanting to become as perfectly female in all ways possible.Growing up without being able to talk about having AIS was stifling to say the least. Closing communication implied great shame, and with the shame came even greater repression. My skate-boarding, baseball card collecting, and model car building interests disappeared after learning about my AIS, which I believe was when I was 12 years old, but I cannot remember exactly. Granted, it’s tough to say whether my interests just changed as I grew older, but I do remember having a fear of portraying any masculine tendencies that other girls in my town weren’t displaying (for example, playing soccer was okay, but I had to shave my legs). I also had crafted some pretty good covers for my AIS, including stories about when I first had my (fake) period, or how I acted fearful about a... (shrink)

During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly‐(ADP‐ribose) polymerase‐1 (PARP‐1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP‐1 itself is induced by DNA damage and is supposed to (...) play a role in DNA repair, these new results suggest a joint role of PARP‐1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP‐1 could provide a co‐ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress. BioEssays 24:1060–1065, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

In this paper we intend, on one hand, to look over the current significance of “indigenismo” in Latin American intellectual field, and on the other, we try to analyze the polemics towards this matter occurred in the 20s. In this way, we will be able to examine the frame in which Mariátegui ´s ..

The article analyzes the project of scientific justification of language Reforms, realized by the Soviet regime in 20s and 30s, elaborated by Russian and Soviet linguist Evgenij Polivanov (1891-1938). Polivanov claims that a Soviet linguist should not limit his interests to the “general linguistics" and become an active “language builder" and “language politician". The reforms should be carefully planned by the experts in language sciences who master as well the methodology of dialectical materialism. In the polemics against Nikolai Marr's Japhetidology (...) Polivanov argued that linguistics is a strict science and its deductions are not contradictory to Marxism, as the latter is primarily a materialist philosophy. His minimal program consisted in explaining his views on the evolution of language in the Marxist terms. The evolution of language is explained by the influence of internal and external factors. The socio-economical factors are not influencing the language in a direct manner, but their analysis allows to change the channel of language evolution. According to Polivanov, the introduction of Marxism into linguistics will make possible to explain the relationship between intralinguistic and extralinguistic factors and will transform the sciences of language into “social engineering of the future". (shrink)

For the New Objectivity art, both literature and paintings, urban reality played a significant role. The aesthetics of the New Objectivity, movement that bloomed in the 20s and 30s, was defined through urban issues. This tendency can be observed primarily in the so-called Zeitroman that became a topic of interest for German literary studies earlier. In contrast to the prose, the New Objectivity poetry was rarely an object of studies. In the article, selected urban verses are analysed and connected with (...) the New Objectivity paintings on a modernist background. (shrink)

The purpose of the study is to reveal the influence of articles about the spontaneous renewal of icons and church domes on the formation of the concept of a miracle among the population of Ukraine on the basis of publications in the Ukrainian press of the early 20s of the XX century. The scientific novelty of the study lies in the fact that for the first time a layer of poorly accessible newspaper publications was analyzed, on the basis of which (...) it was established what information background was formed around rumors about miracles that occurred in 1920-1925, and how it could influence the emergence of the corresponding narratives. As a result, it was revealed that stories about miracles in Ukraine during this period were characteristic of both rural and urban environments, and affected almost all layers of society, including the emergence of a stratum of the population that ironically laughed at miracles. It is shown that miracles very quickly entered into everyday reality, and they ceased to see supernatural features. Concrete examples demonstrate that miracles in this period increasingly began to be left to the mercy of science and technology. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Reading After Actium: Vergil's Georgics, Octavian, and RomeSergio CasaliChristopher Nappa. Reading After Actium: Vergil's Georgics, Octavian, and Rome. Ann Arbor: University of Michigan Press, 2005. xii + 293 pp. Cloth, $75.Nappa's reading of the Georgics is a linear one: in his own words, his book is "a literary commentary that moves sequentially through the text from beginning to end" (3). After the introduction, the book is divided into (...) four chapters, each one devoted to a single book of the poem. This is how Nappa presents his work: "It is my contention that the Georgics can be profitably understood as a post-Actium 'reading,' or rather a set of them, of the situation in which Octavian found himself in the early 20s b.c.e., after the battle of Actium and before the assumption of the title Augustus. Perhaps more importantly, the Georgics represents an attempt to engage in a constructive dialogue with Octavian on the potential courses available to him and on the potential interpretations of his character, achievements, and motives, which would have been a central concern to the Roman and Italian elite"; Nappa wants to read the Georgics "as a didactic work addressed to Octavian, one that invites him (and any other reader) to react to specific problems, puzzles, and challenges" (1–3).From these proemial declarations I was expecting a linear reading of the poem constantly focused on Octavian as the model reader of the text, a consistent attempt to imagine his reactions as the "disciple" of Vergil. In fact, Nappa does not do that, at least not in a fully consistent way. Octavian as the ideal disciple and the poem as a series of "lessons" to the princeps are only a part of Nappa's actual reading of Vergil's text. I must confess that this discovery has been a bit disappointing, especially since the first chapter does in fact rather brilliantly begin with a lesson to Augustus; but this is due to the fact that the poem, of course, opens with an invocation to the princeps. Unfortunately, after that Octavian will not always be the center of attention, as I was hoping. But this does not mean that Nappa does not have interesting things to say about Vergil's poem.The introduction (1–22) clarifies Nappa's avowedly reader-oriented approach to Vergil's text: he proposes to confront the poem's difficulties and contradictions as, in a sense, the real meaning of the text: "the lessons of the [End Page 611] Georgics do not consist of the transmission of information but of the experience of confronting the often chimerical world presented by the poet.... the Georgics emphasizes the fact that in our quest for a meaning various audiences will construct (or discover) different, and even mutually exclusive meanings" (3). After a defense of intentionality as a heuristic tool for reading the Georgics, Nappa discusses the complex status of Octavian in the poem. First of all, he is the poem's addressee, "the most important audience Vergil has ever had," to whom to poet address even harsh lessons ("Octavian must understand the nature of the world he is trying to govern and the way the world sees him," 6); but he is also one of the topics of discussion, and at the same time one of the gods who are asked to favor the poet's undertaking. For Nappa, "the poem does not express a view of the princeps or his achievements so much as it invites the audience, Octavian as well as us, to consider the theme from multiple points of view" (8). Vergil's famous "mistakes" also "serve a didactic purpose: by inviting his readers to consider agricultural advice that is either obviously erroneous or presented in a highly selective and nonsequential way, the teaching poet compels them to search for deeper meaning, a term I use with some reluctance. The meaning each reader finds will, of course, depend on that reader" (11). In the last section of the introduction, Nappa locates the position of his reading within recent scholarship on the Georgics: his aporetic stance recalls above all Christine Perkell, The Poet's Truth (Berkeley... (shrink)

: The Kehre in Heidegger’s thought has been greatly discussed and debated. The introduction of the notion of metontology in 1927 has fruitfully informed this debate since it entails a concern for the ontic domain on the part of Heidegger that is not present in earlier works. The fact that this notion disappears right after being introduced, however, challenges its contribution to this debate. In this paper, I show that the disappearance of metontology does not imply the disappearance of Heidegger’s (...) concern for the ontic, but the opposite. I will begin by presenting Freeman’s view of a tension between the ontic and the ontological in Heidegger’s thought in the mid-to-late 20s that results in the introduction of metontology in 1927. Later on, I will show that McNeill’s explanation of the disappearance of metontology as a consequence of Heidegger’s mid-30s view that the a priori projection of being is a withdrawal of being, allows saying that this disappearance does not entail Heidegger’s sudden lack of concern for the ontic. By considering Heidegger’s analysis of ‘the mathematical’ in Die Frage nach dem Ding, I will finally argue that metontology disappears from Heidegger’s thought because its dependency upon ontology prevents it to account for his increasing concern for the ontic properly. Resumo: A Kehre no pensamento de Heidegger foi amplamente discutida e debatida. A introdução da noção de metontologia, em 1927, informou proveitosamente esse debate, uma vez que implica uma preocupação com o domínio ôntico, por parte de Heidegger, que não está presente em trabalhos anteriores. O fato de essa noção desaparecer logo após ser introduzida, porém, desafia sua contribuição para esse debate. Neste artigo, mostra-se que o desaparecimento da metontologia não significa o desaparecimento da preocupação de Heidegger com o ôntico, mas o contrário. Começa-se apresentando a visão de Freeman de uma tensão entre o ôntico e o ontológico, no pensamento de Heidegger, em meados da década de 1920, que resulta na introdução da metontologia, em 1927. Mais tarde, evidencia-se que a explicação de McNeill para o desaparecimento da metontologia, como consequência da visão de Heidegger, de meados dos anos 30, de que a projeção a priori do ser é uma retirada do ser, permite dizer que esse desaparecimento não acarreta uma repentina falta de preocupação de Heidegger com o ôntico. Ao considerar a análise de Heidegger de “o matemático”, em Die Frage nach dem Ding, finalmente, argumenta-se que a metontologia desaparece do pensamento de Heidegger, porque sua dependência da ontologia a impede de explicar sua crescente preocupação com o ôntico, de maneira adequada. (shrink)

Background There is continued need for enhanced medical ethics education across the United States. In an effort to guide medical ethics education reform, we report the first interprofessional survey of a cohort of graduate medical, nursing and allied health professional students that examined perceived student need for more formalized medical ethics education and assessed preferences for teaching methods in a graduate level medical ethics curriculum. Methods In January 2018, following the successful implementation of a peer-led, grassroots medical ethics curriculum, student (...) leaders under faculty guidance conducted a cross-sectional survey with 562 of 1357 responses received among students enrolled in the School of Medicine, College of Nursing, Doctor of Physical Therapy and BS/ MD Professional Scholars programs at The Medical College of Georgia at Augusta University. An in person or web-based questionnaire was designed to measure perceived need for a more in-depth medical ethics curriculum. Results The majority of respondents were female, white and mid-20s in age. Almost half of respondents reported no prior medical ethics exposure or training in their previous educational experience, while 60% of students across all degree programs reported an interest in more medical ethics education and 92% noted that an understanding of medical ethics was important to their future career. Over a quarter of students were interested in pursuing graduate-level training in medical ethics, with case-based discussions, small group peer settings and ethics guest lectures being the most desired teaching methods. Conclusions The future physician, nursing and physical therapist workforce in our medical community demonstrated an unmet need and strong interest for more formal medical ethics education within their current coursework. Grassroots student-driven curricular development and leadership in medical ethics can positively impact medical education. Subsequent integration of interprofessional training in medical ethics may serve as a vital curricular approach to improving the training of ethically competent healthcare professionals and overcoming the current hierarchical clinical silos. (shrink)

This paper contemplates Organicism and its relation with molecular and evolutionary biology. We explore whether twentieth-first century biology is returning to positions held at the beginning of the twentieth century and then abandoned. The guiding line is a history of theoretical biology in which we distinguish three periods: 1. The 20s-30s, and the Theoretical Biology Club (Needham, Woodger, and Waddington, among others); 2. An intermediate period in the 60s-70s, in which, in spite of the eclosion of the molecular and evolutionary (...) biologies, there is some recovery of organicist positions, and 3. The present post-genomic situation, which is demanding a systemic approach. (shrink)

ABSTRACT. This paper contemplates Organicism and its relation with molecular and evolutionary biology. We explore whether twentieth-first century biology is returning to positions held at the beginning of the twentieth century and then abandoned. The guiding line is a history of theoretical biology in which we distinguish three periods: 1. The 20s-30s, and the Theoretical Biology Club (Needham, Woodger, and Waddington, among others); 2. An intermediate period in the 60s-70s, in which, in spite of the eclosion of the molecular and (...) evolutionary biologies, there is some recovery of organicist positions, and 3. The present post-genomic situation, which is demanding a systemic approach. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Beginning in the 20s of the last century, historical research into Eiximenis's life and writings has thrown into relief his contribution to the language and political ideas of the kingdoms and towns of the Catalan-Aragonese Crown. Of fundamental importance has been the work of medievalists from North America, and in particular that of Canadian scholars during the last decades of the twentieth century.More recently, a number of studies have (...) underlined the decisive contribution of Eiximenis – a representative of a European textual tradition among friars of the Minor Observance that extended from Oxford to Florence – to the establishment of a system of ethical values for the economic sphere and for trading practices that continued to be developed by members of the Franciscan Order throughout the high middle ages and early modern period.As a follow-up to these studies, I believe that a program of textual analysis and systematic investigation of Eximenis's work could provide further information about the range and significance of his political thinking, based as it was on applying, in typically Franciscan fashion, experimental observation to gain an understanding of the nature both of the societas and of the market, the latter being thought of as a defining expression of civic institutions in Western Europe. This same experimental approach can be found in Franciscan thinking from the catalan-aragonese realm not only in the work of Arnau de Vilanova and Ramon Llull, but also in that of Pere Tomas and Anselm Turmeda, two figures fundamental to the preparation and political engagement of the Friar of Girona.1. The concept of contractIn Eiximenian texts, the communitarian dimension is defined as one that is of necessity based on contract. It is expounded in the long opening section of the Dotzè del Crestià, where Eiximenis outlines the political value of the civitas, as well as setting out the elements that constitute civic life.Borrowing from Aristotle's discussion in the First Book of the Politics , the Franciscan friar strongly affirms that one of the principal reasons behind the civitas is the "necessitat de contractes," the need for contracts. Going far beyond the highly qualified analysis of money and coinage set out by the Greek philosopher, Eiximenis here maintains that the aims of the community is the profit that the citizenry realises by means of different forms of exchange, through buying and selling, through contracts, and through trading. Moreover, that the binding nature of trading-contracts is a matter of concern not of the city in the narrow sense, but of each and every kind of human social organization.Even before contract-law, or, better said, conventional or foral procedure, Eiximenis views the idea of the contract as an essential part of the ethical and organizational principles of living as a community, the essence of the civitas. And it is of great significance that when he is discussing the value and function of money, Eiximenis chooses to call the sorts of exchange that to-day we term economic or financial les civils conmutacions, or exchanges between citizens.These lexical hints allow us to capture the strength of meaning and value, the ethical perspective by which the Gerundense defines the inextricable union of the market and civic society. But it is not only an analytical perspective, significant as that is, that unites market and civic ethics; we are presented with a value judgment of contract and economic exchange as elements that determine the very idea of civilitas.The "bona civilitas," an expression that can be roughly translated as "good civic culture," is in fact founded on a concept of economic ethics that has as its distinguishing feature the logic of profitable exchange, of the distribution of that profit, of contractualization, and of the circulation of goods and money. It is characterised by redefining the anti-value of avaritia as a real.. (shrink)

The proteasome family of proteases comprises oligomeric assemblies of very different symmetry. In different sizes, it features ring‐like oligomers with dihedral symmetry that allow the stacking of further rings of regulatory subunits as observed in the modular proteasome system, but also less symmetric helical assemblies. Comprehensive sequence and structural analyses of proteasome homologs reveal a parsimonious scenario of how symmetry may have emerged from a monomeric ancestral precursor and how it may have evolved throughout the proteasome family. The four characterized (...) representatives—ancestral β subunit (Anbu), HslV, betaproteobacterial proteasome homolog (BPH), and the 20S proteasome—are outlasting cornerstones in the family's evolutionary history, each marking a transition in symmetry. This article contextualizes the evolutionary and functional key aspects of these symmetry transitions, explaining how they facilitated the diversification and concurrent evolution of independent proteolytic systems side by side, each with its customized network of auxiliary interactors. -/- . (shrink)