Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. (...) S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. (shrink)

The eleventh-century Indian Buddhist master Ratnākaraśānti presents a unique Yogācāra interpretation of tantric _maṇḍala_ visualisation in the _*Guhyasamājamaṇḍalavidhiṭīkā_. In this text, he employs the neither-one-nor-many argument to assert that the qualities of the mind represented by the deities in the _maṇḍala_ are neither the same nor different from the mind itself. He also provides five scenarios of meditation to explain the necessity of practising both the perfection method (_pāramitānaya_) and the mantra method (_mantranaya_) together in Mahāyāna. Ratnākaraśānti’s explanation exerts a (...) significant influence on the works of later Buddhist masters in India and Tibet, with parts of it being reused in the _*Śrīherukopadeśanāmasvādhiṣṭhānakrama_ by Śūnyasamādhivajra (c. the eleventh century), the eighteenth chapter of the _Āmnāyamañjarī_ by Abhayākaragupta (from the late eleventh to the twelfth century) and the tantric compendium _sNgags rim chen mo_ by the Tibetan master Tsong kha pa Blo bzang grags pa (1357–1419). This paper explores how Ratnākaraśānti’s explanation has been reused and modified in these subsequent works. While Śūnyasamādhivajra faithfully reproduced Ratnākaraśānti’s Yogācāra explanation, Abhayākaragupta modified it to align with his Madhyamaka view. Abhayākaragupta in turn influenced Tsong kha pa, who accepted Abhayākaragupta’s Madhyamaka modification in his works. This paper also engages with current scholarly discussions on textual reuse and the underlying reasons behind it. While Śūnyasamādhivajra and Abhayākaragupta assimilated Ratnākaraśānti’s explanation without acknowledgement, Tsong kha pa quoted the text by name and acknowledged Abhayākaragupta’s reuse of Ratnākaraśānti’s explanation. This paper concludes by discussing the factors that determine whether the reused text is acknowledged or not, and the possible reasons behind textual reuse. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Inspiration and Institution in John of Rupescissa's Liber Ostensor XI1Graziana S. CiolaIntroductionThe present study proposes a philosophical analysis of John of Rupescissa's Liber Ostensor [=LO], Treatise XI. John of Rupescissa (OFM, 1310 ca. – 1366)2 is a particularly interesting, eclectic and somewhat extraordinary [End Page 7] author writing around the second third of the 14th century in the wake of the Spiritual Franciscan movement in the South of France.3 (...) In LO XI, Rupescissa theorizes and systematically articulates a complex relationship between inspired knowledge and the normative portrait of what he believes the Franciscan Order should ideally be; he does so against the background of his eschatological concerns. Per Rupescissa's style of exposition and argumentation, these different elements — i.e., inspired epistemology, eschatology, and ecclesiology — are tightly intertwined on a theoretical and foundational level that goes beyond that of mere rhetorics.These themes are both recurrent and pivotal throughout Rupescissa's extremely prolific intellectual output, which counts numerous theological, ecclesiological, eschatological and alchemical treatises.4 LO, composed in [End Page 8] 1356 during Rupescissa's own "Avignon Captivity," is in many ways a sum of Rupescissa's prophetical and eschatological thought within the framing of the author's self-apologetic aims and of his ecclesiological views, in particular concerning the future of the Franciscan Order.5 [End Page 9]Treatise XI is undoubtedly the most theoretical book in LO; with its 489 paragraphs, it is also the longest. While this extremely dense text broaches on a great variety of topics, it is first and foremost about and for Spiritual Franciscans. Overall, LO XI is both a great portrayal of the Franciscan order as it is and as it should be, as well as a handbook addressed to the elect among the Spirituals, in order to help them face the eschaton and the tribulations to come. Per Rupescissa's eschatological views, such trials would affect the Franciscan Order the hardest and for the longest — hence the need for a detailed guide. At its core, then, LO XI is a deeply ecclesiological treatise and as such it is complementary to the larger systematization established in the Sexdequiloquium.6 It is in this framework that LO XI offers a complex theory of prophecy and illuminative knowledge as they should be embodied in the practices of a true Franciscan.7Given its highly abstract nature and cardinal function within one the most complex works of Rupescissa's maturity, LO XI, combining relevant insights on Rupescissa's ecclesiological, epistemological and prophetical positions, constitutes the ideal case study in order to assess Rupescissa's most refined and articulated account on inspired knowledge, particularly insofar as true and actual prophecy is concerned. This inspired knowledge, according to Rupescissa, is an indispensable tool for the elect to be able to victoriously face the imminent end of times. In the account presented in LO XI, such knowledge is possible exclusively through a form of institutional embedding: divine inspiration, culminating in true prophecy, is in service of the Franciscan Order's soteriological role within the Church as a whole, and can only be achieved by those who are faithful to the spirit of Francis's Rule.8 [End Page 10]Here, I analyze Rupescissa's theory of evangelical poverty and its role as a necessary condition for inspired knowledge, following the internal articulation of LO XI.Overall, in Rupescissa's view, Franciscan poverty and inspiration are two inseparable sides of the same coin. On the one hand, inspired knowledge is only achievable through a rigorous practice and thorough understanding of Franciscan poverty. On the other hand, the true institutional role of the Franciscan Order and its soteriological aims can be fulfilled exclusively by the true Spiritual Franciscans, whose moral, spiritual and epistemic perfection is divinely inspired. For Rupescissa, not only is poverty the source of all virtues both for the Franciscan Order and for the rest of the Church, but it also constitutes the ideal moral and social model, tout court. But most importantly, evangelical poverty has a genuinely epistemic role; this role is essential for Rupescissa's illuminative epistemology and for his account of prophetical exegesis — or exegetical prophecy. In turn, the... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:A Commonwealth of Hope: Augustine’s Political Thought by Michael LAMBMichael J. S. BrunoLAMB, Michael. A Commonwealth of Hope: Augustine’s Political Thought. Princeton, N.J.: Princeton University Press, 2022. xiii + 431 pp. Cloth, $39.95In his comprehensive study of Augustinian hope, Michael Lamb seeks to provide a corrective to the common characterization, especially promoted in the last century, of Augustine as politically and socially pessimistic. Lamb asserts that Augustine’s work (...) leads us, rather, to a “realistic hope,” as he argues for a more “hopeful, this-worldly” reading of the Doctor of Grace. After tracing the path of contemporary Augustinian interpretation, Lamb begins an interdisciplinary study of Augustine’s understanding of hope, which he argues allows us to understand how Augustine “advocated and modeled engagement in public life,” as “bishop, theologian, and citizen.”In part 1, “The Virtue of Hope,” Lamb systematically discusses Augustine’s understanding of virtue, and the relationship within his theology of the theological virtues. In chapter 1, Lamb utilizes the Enchiridion to explore Augustine’s understanding of the objects and grounds of hope, as “the orientation of will” toward objects that “engage our desire and spark an affective movement for union with what we love.” In chapter 2, Lamb explores hope’s integral connection to love and integrally captures key concepts in Augustine’s thought, particularly the consequences of the Fall in human pride, the presence of the libido dominandi, and the often-discussed debate of uti-frui, noting that Augustine is fundamentally concerned with love being rightly ordered. In chapter 3, he responds to the criticism of Augustine’s hope as “otherworldly,” explaining how Augustine does not dismiss temporal goods but, rather, “chastens disordered desires for them.” Lamb also makes clear that Augustine “challenges the either/or dualism” that locates [End Page 154] eternal goods in a purely transcendent realm. In chapter 4, Lamb analyzes the grounds of faith and its objects, outlining Augustine’s treatment of faith’s relation to both authority and neighbor, who for Augustine must be included as an object of faith. In chapter 5, relying on Augustine’s Confessions, Lamb underscores the condemnation of Pelagianism while demonstrating that similar to love, we might hope in neighbors as “a way to hope in the invisible God.” He also examines the epistemological challenges presented by the vices of presumption and despair, noting how for Augustine “a deficient or disordered faith leads to disordered hope.”Part 2 of Lamb’s work turns to Augustine’s rhetoric and how Augustine’s pedagogical concerns undergird both his sermons and other works, especially the often-cited City of God. In chapter 6, Lamb notes the need within political interpretations of Augustine for a greater grasp of “his rhetorical and pedagogical purposes,” especially his moral teaching offered to a wide and diverse audience both in his preaching and letters. In chapter 7, Lamb turns to City of God, noting its aim as both instruction and encouragement, and confronts the limits of the binary view of optimism and pessimism as “anachronistic and conceptually confining.” Lamb, on the contrary, posits a “more capacious triad of presumption, hope, and despair” as capturing the true “posture” of Augustine’s City of God, especially book 22.In part 3, Lamb focuses on the place of political goods as objects of hope within Augustine’s thought. Chapter 8 focuses on the political implications of Augustine’s eschatology and ecclesiology and, through engagement with numerous interpreters, examines Augustine’s saeculum as “a passing age in which members of both cities—earthly and heavenly—share proximate goods and build a common life together.” In chapter 9, Augustine’s epistolary is examined in order to demonstrate that, while “fulfilling his duties and embodying active citizenship, [Augustine] did not make an idol of politics or see it as the ultimate source of salvation.” In chapter 10, Lamb proposes an alternative account to the “antipolitical, otherworldly exclusivist” Augustine, namely, an Augustine who both is slow to judge the virtue and vice of others and acknowledges “some form of genuine, if incomplete, virtue in those without faith.” In this chapter, Lamb’s nuances of Augustine’s understanding of “true virtue” are well grounded... (shrink)

Surgeons are commonly evaluated with respect to outcomes and adherence to rules and regulations, rather than a true holistic examination of the character of the surgeon in question. We sought to examine the character failings of surgeons who faced fitness to practice enquiries under the Medical Practitioner Tribunal Service in the UK. In particular, we examined the absence of virtue as perceived through the lens of Aristotelian ethics using thematic analysis of tribunal hearing transcripts from 2016 to 2020. We identified (...) three overarching themes that are explored in depth: ‘the god complex’, ‘reputation over integrity’ and ‘wounded pride’. We hope to use this as the foundation for a re-examination of the place of phronesis in postgraduate surgical education, which we argue should be perceived as an exercise in character development and reformation rather than the simplistic teaching of skills to standardised outcomes. (shrink)

In this essay, the author analyses Berkeley’s conformity and inference argument against Locke’s theory of percep tion. Both arguments are not as decisive as traditionally has been perceived and fail to engage in Locke’s actual position. The main reason for this is that Berkeley does not see that Locke’s position is compatible with the non-inferential nature of perceptual knowledge.

On educational thoughts of Rabindranath Tagore, 1861-1941, Bengali litterateur and Mahatma Gandhi, 1869-1948, Indian statesman and nationalist.

On the philosophy of death in Hindu traditions; study based on Mr̥tyupurāṇa of Svāmī Mr̥tyujayānanda.

Abstractp53 is a multifunctional protein which plays a role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability and responding to genetic insults. Mutation of the p53 gene confers the single greatest known selective advantage favoring cancer formation. Point mutations result not only in the loss of tumor suppressor functions, but also in the gain of tumor promotion functions. These dual circumstances may be unique to p53 and, in part, could explain (...) the relatively powerful force behind this selection pressure. General mechanisms of gain of function by mutated p53 may include alteration in transcriptional modulation and newly acquired targets for transcriptional regulation and protein binding. Despite the direct significance of p53 mutations, loss of the remaining wild‐type allele is usually required for the formation of tumors in the natural setting. Novel applications of the basic scientific knowledge of p53 could lead to an improvement in cancer treatment, hopefully in the not so distant future. (shrink)

Turkey’s interests in the Arab world have significantly changed, three times, over the last century. Changes in political power in the geography of Anatolia involved a shift in political interests in some sense; sometimes the issue of Arab geography and states was dropped from the list of priorities but then brought back to that list again. Although at the time of the Ottoman Empire, the state of the Muslim world was considered a priority, during the republic it was removed from (...) the agenda. However, in the 21st century, it has again become an integral part of Turkey’s foreign policy. (shrink)

The tumor suppressor protein p53 is intimately involved in the cellular response to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45, was recently found to bind to PCNA, a component of DNA replication/repair complexes, thereby implicating Gadd45 in DNA metabolism(1). Using biochemical assays, a role for Gadd45 in excision repair in vitro has been demonstrated(1). Antisense experiments have also indicated an in vivo role for the GADD45 (...) gene in UV‐irradiation survival. These discoveries establish a link between p53 and DNA repair through Gadd45. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Cognition and Practice: Li Zehou's Philosophical Aesthetics by Rafal BankaJana S. Rošker (bio)Cognition and Practice: Li Zehou's Philosophical Aesthetics. By Rafal Banka. Albany, New York: SUNY, 2022. Pp. vii+ 230. Hardcover $95,00, isbn 978-1-4384-8923-4. In his book Cognition and Practice: Li Zehou's Philosophical Aesthetics, Rafal Banka delves into the cognitive philosophy of Li Zehou, one of the most significant and influential Chinese philosophers of our time. Banka not (...) only provides a deeper understanding of Li's work, but he also places his studies on beauty and aesthetic experience in close proximity to current international research in philosophical aesthetics that places great importance on the embodiment and embeddedness of the subject. By delving into Banka's analysis of the cognitive dimensions of Li Zehou's aesthetics, readers can gain a deeper understanding of how this philosopher approaches the intersection of aesthetics and cognition. Through Banka's interpretation, Li's specific view on the intricate relationship between sensory perception and mental processes is highlighted, offering readers the potential for a more nuanced conception of his philosophical perspective. Banka's contribution to our understanding of Li's theories of cognition is deeply intertwined with the methodological framework and theoretical approach used in his work. The former is based upon an analytical perspective that enables him to identify key themes and concepts in Li's cognition theory, as well as to critically evaluate the strengths and weaknesses of his approach. By employing this framework, Banka provides a comprehensive and nuanced analysis of Li's cognitive dimensions that is grounded in rigorous examination. In addition to the methodological framework, the comprehensive theoretical approach that Banka applies in his study is also integral to understanding Li Zehou's contribution to the theory of perception on an international level. The book is divided into three distinct parts, each of which explores a different aspect of Li's philosophy. In the first part, Banka examines Li's main sources of inspiration, specifically the philosophers and philosophies that have significantly influenced and contributed to his own work. This section primarily focuses on classical Confucianism, Marxist historical materialism, and Li's unique reinterpretations of Immanuel Kant's philosophies, particularly those presented in his second and third critiques. [End Page 1]In the first three chapters that constitute this first part, Banka offers a clear and comprehensive analysis of how Li Zehou has viewed Kant's apriorism through the lens of Confucianism and integrated it with Marxist materialist foundations, revealing the coherence with his theory of anthropological ontology. By highlighting the interconnectedness of these diverse influences, Banka illuminates the unique synthesis of ideas that form the foundation of Li's philosophy. Through his detailed analysis, Banka shows how Li Zehou managed to create a synthesis between the dynamic elements of historical materialism on the one hand, and Kant's transcendentalism on the other. In Li's system, the concepts of the empirical and the transcendental are interacting in a dynamic, correlative and mutually complementary way. They are both parts of a processual philosophy in which movement is always followed by a standstill. In such a worldview, they always appear as essentially interrelated and interdependent realms of life. Banka provides a comprehensive explanation of the theoretical foundations that underpin the interactive and complementary nature of these two systems. This has culminated in the development of Li's groundbreaking new theory on the transformation of the empirical into the transcendental. In the second part of the book, the author delves into Li's own philosophical system, specifically focusing on his concepts of "subjectality" and beauty. These concepts are not axiologically theorized but instead arise from subjective interactions between human beings and the external world. Through a detailed and logically consistent analysis, the author demonstrates how Li's aesthetics is compatible with contemporary experience-oriented theories that are redefining the discipline on an international level. In chapters 4 and 5, the much-discussed concept of subjectality is viewed from a highly productive perspective, starting from the very center of the notion itself, where a subject actively interacts with the external reality, which in turn shapes its inwardness. The author convincingly demonstrates... (shrink)

John, Qumran, and the Dead Sea Scrolls: Sixty Years of Discovery and Debate. Edited by Mary l. Coloe and Tom Thatcher. Early Judaism and Its Literature, vol. 32. Atlanta: Society of Biblical Literature, 2011. Pp. xiii + 228. $28.95.

Our study presents an overview of the issues that were brought forward by participants of a moral case deliberation (MCD) project in two elderly care organizations. The overview was inductively derived from all case descriptions (N = 202) provided by participants of seven mixed MCD groups, consisting of care providers from various professional backgrounds, from nursing assistant to physician. The MCD groups were part of a larger MCD project within two care institutions (residential homes and nursing homes). Care providers are (...) confronted with a wide variety of largely everyday ethical issues. We distinguished three main categories: ‘resident’s behavior’, ‘divergent perspectives on good care’ and ‘organizational context’. The overview can be used for agendasetting when institutions wish to stimulate reflection and deliberation. It is important that an agenda is constructed from the bottom-up and open to a variety of issues. In addition, organizing reflection and deliberation requires effort to identify moral questions in practice whilst at the same time maintaining the connection with the organizational context and existing communication structures. Once care providers are used to dealing with divergent perspectives, inviting different perspectives (e.g. family members) to take part in the deliberation, might help to identify and address ethical ‘blind spots’. (shrink)