The dynamics of eukaryotic DNA polymerases has been difficult to establish because of the difficulty of tracking them along the chromosomes during DNA replication. Recent work has addressed this problem in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of replicative polymerases to render them prone to incorporating ribonucleotides at high rates. Their use as tracers of the passage of each polymerase has provided a picture of unprecedented resolution of the organization of replicons and replication origins in the (...) two yeasts and has uncovered important differences between them. Additional studies have found an overlapping distribution of DNA polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA. This sequence instability is caused by the premature release of polymerase δ and the retention of non proof‐read DNA tracts replicated by polymerase α. The possible implementation of these new experimental approaches in multicellular organisms opens the door to the analysis of replication dynamics under a broad range of genetic backgrounds and physiological or pathological conditions. (shrink)

Numerous reports have noted decreasing numbers of antibiotic approvals. To determine the context for this decline, we examined all new molecule entities (NMEs) and new biologic licenses (NBLs) approved by the FDA from 1980–2009, and compared approval rates of the 61 approved antibiotics to trends in other drug classes. We also tracked withdrawals of approved drugs and found more withdrawals for antibiotics than other drug classes. After adjusting for drugs subsequently withdrawn, the record for antibiotic innovation is less dire than (...) previously reported. We also report problems with the quality of the approved antibiotics studied. Future policies providing incentives for new antibiotic development should not be based on simple numerical targets and key provisions should ensure appropriate quality as well as quantity of antibiotic drug innovation. (shrink)

Antibiotic use triggers evolutionary and ecological responses from bacteria, leading to antibiotic resistance and harmful patient outcomes. Two complementary strategies support long-term antibiotic effectiveness: conservation of existing therapies and production of novel antibiotics. Conservation encompasses infection control, antibiotic stewardship, and other public health interventions to prevent infection, which reduce antibiotic demand. Production of new antibiotics allows physicians to replace existing drugs rendered less effective by resistance.In recent years, physicians and policymakers have raised concerns about the pipeline for new antibiotics, pointing (...) to a decline in the number of antibiotics approved since the 1980s. This trend has been attributed to high research and development costs, low reimbursement for antibiotics, and regulatory standards for review and approval. Professional societies and researchers around the world have called for renewed emphasis on antimicrobial stewardship, while also supporting antibiotic research and development through grants, changes to intellectual property laws to extend market exclusivity periods, and modification of premarket testing regulations to reduce antibiotic development time and expenses. (shrink)

Resumen En este artículo expongo los aspectos principales del debate suscitado por la aparición del libro de Adolfo Sánchez Vázquez Ciencia y revolución: el marxismo de Althusser. Presentaré primero la crítica del filósofo hispanomexicano a la obra de Louis Althusser y después explicaré la contracrítica del también filósofo Enrique González Rojo que aparece en su libro Epistemología y socialismo. Por último, ofrezco una interpretación de ambos momentos que las concibe como partes de un capítulo significativo de la historia (...) de la filosofía en México.In this article I present the main points of a debate raised by the book Science and Revolution: The Marxism of Althusser by Adolfo Sánchez Vázquez. I begin by addressing the criticism of the Spanish-Mexican philosopher towards the work of Louis Althusser and then I explain the counter-criticism to this approach set forth by -the also philosopher- Enrique González Rojo in his book Epistemology and Socialism. Finally, I offer an interpretation in which both moments in the debate are conceived as a significant chapter in the history of philosophy in Mexico. (shrink)

Software vulnerabilities are the root cause for a multitude of security problems in computer systems. Owing to their efficiency and tight control over low-level system resources, the C and C++ programming languages are extensively used for a myriad of purposes, from implementing operating system kernels to user-space applications. However, insufficient or improper memory management frequently leads to invalid memory accesses, eventually resulting in memory corruption vulnerabilities. These vulnerabilities are used as a foothold for elaborated attacks that bypass existing defense methods. (...) In this paper, we summarise the main memory safety violation types (i.e. memory errors), and analyse how they are exploited by attackers and the main mitigation methods proposed in the research community. We further systematise the most relevant techniques with regards to memory corruption identification in current programs. (shrink)

The ancient Stoics proposed one of the most sophisticated and influential ethical frameworks in the history of philosophy. Its impact on theory and practice lasted for centuries during the Hellenistic and Roman periods. Today, their arguments and theories still inform many contemporary ethical debates. Moreover, some of the framework’s main tenets have been used as a theoretical foundation for cognitive–behavioural therapy (CBT), a widely used psychosocial intervention for improving mental health. Much of its lasting impact is the result of the (...) special attention Stoic ethics pays to moral psychology, action theory and education. Stoics consider one of the main components of the development of virtue to be a careful and systematic training of our desires and aversions. -/- This chapter will offer a clear, succinct and up-to-date discussion of four main topics: (1) the Stoic theory of desire; (2) the complex taxonomies of desire offered by the ancient Stoics; (3) the arguments, educational strategies, and practices the Stoics recommend to discipline our soul and extirpate our irrational desires and finally (4) a brief discussion of the possibility of adapting the Stoic philosophy for the education of desires in the present day. (shrink)

Esta obra se abre con una introducción histórica, no heleno ni eurocéntrica, en la que se reinterpretan los sistemas éticos en la historia mundial, hasta situar la problemática en la Modernidad dentro del sistema-mundo como proceso de globalización que simultáneamente excluye a la mayoría de la humanidad. En la primera parte se aborda una crítica a las morales formales (Kant, Rawls, Apel, Habermas) desde un principio material o de contenido con pretensión de universalidad; el deber de producir, reproducir y desarrollar (...) la vida humana en comunidad. El principio de factibilidad ética, por su parte, permite que el cumplimiento del acto, institución o sistema de eticidad pueda tener la pretensión de bondad. En la segunda parte, desde la imposibilidad de que dicho acto, institución o sistema de eticidad «buenos» pueda tener pretensión de perfección acabada, se descubren los que «sufren» en su corporalidad vulnerable la imposibilidad de vivir, el hecho de ser excluidos. Se trata de las víctimas, al decir de Marx, Horkheimer, Benjamin, Nietzsche, Freud o Lévinas. Desde las víctimas comienza propiamente el discurso de la Ética de la Liberación, en su nivel negativo material (deben poder vivir), en el principio discursivo crítico (deben poder participar en la argumentación), todo lo cual culmina en el principio crítico negativo de la factibilidad: el principio-liberación que inspira las transformaciones con pretensión de justicia. (shrink)

The book presents insights from a mixed methodology study that examines recent mobility patterns exhibited by the middle classes. Its major contributions are two-fold: theoretically, it advances the conceptualisation of middle class migration; empirically, it analyses the migratory motivations of a relatively new Latin-American group in Australia. The accelerated insertion of the Mexican society into globalisation processes is strongly linked not only to the growing participation in migration phenomena but also to people's outflow to new destinations. Although studies of Mexican (...) emigration are vast, research on Mexican skilled migration is scarce, and research that focuses on mobility to non-USA destinations is even scarcer. Mexicans are a relatively new addition to Australia's multicultural society, and little is known about this group's profile and why they choose to migrate to Australia. Employing a mixed methodology approach, the book provides a comprehensive portrait of migration in a new group. (shrink)

The aim of this paper is to explore the peculiar case of infectious logics, a group of systems obtained generalizing the semantic behavior characteristic of the -fragment of the logics of nonsense, such as the ones due to Bochvar and Halldén, among others. Here, we extend these logics with classical negations, and we furthermore show that some of these extended systems can be properly regarded as logics of formal inconsistency and logics of formal undeterminedness.

El presente artículo intenta ofrecer un marco documental para la discusión sobre la estructura cosmológica de Ferecides de Siros. Partiendo de la polémica entre quienes le adjudican un cosmograma quinario y aquellos que lo interpretan septenario, proponemos un recorrido por las antiguas doctrinas cosmológicas quinarias, tanto griegas como orientales, a fin de explorar su recurrencia y variedad. Se constata que la disputa religiosa entre los apologetas del cinco y los del siete existía ya en la antigüedad, pudiendo haber afectado a (...) la lectura que los doxógrafos hicieron entonces de la obra de Ferecides. Se expone la teoría de Nick Allen sobre la existencia de una «ideología pentádica» indoeuropea y se critica su sesgo idealista (pitagórico en la línea de Dumézil). Finalmente, se suscribe la hipótesis del origen «protogeométrico» de muchos de estos mapas ontológicos quinarios y se recapitulan las posibles referencias que manejaba el maestro de Pitágoras cuando ideó su teogonía. (shrink)

In The Theological Metaphors of Marx, Enrique Dussel provides a groundbreaking combination of Marxology, theology, and ethical theory. Dussel shows that Marx unveils the theology of capitalism in his critique of commodity fetishization. Capitalism constitutes an idolatry of the commodity that undergirds the capitalist expropriation of labor. Dussel examines Marx's early writings on religion and fetishism and proceeds through what Dussel refers to as the four major drafts of Capital, ultimately situating Marx's philosophical, economic, ethical, and historical insights in (...) relation to the theological problems of his time. Dussel notes a shift in Marx's underlying theological schema from a political critique of the state to an economic critique of the commodity fetish as the Devil, or anti-God, of modernity. Marx's thought, impact, and influence cannot be fully understood without Dussel's historic reinterpretation of the theological origins and implications of Marx's critiques of political economy and politics. (shrink)

Background: The prevalence of anxiety and depression in young students is associated with biosocial factors and scholastic stress. However, few studies have evaluated emotional-affective symptoms that are related to the immune system and antioxidant parameters in young individuals without diagnoses of affective disorders.Aim: This study aims to assess the relationship between emotional-affective symptoms and glutathione concentrations and CD4 and CD8 lymphocyte counts in college students.Methods: College students completed standardized psychometric instruments, including the Perceived Stress Scale, Hamilton Anxiety Scale, Beck Depression (...) Inventory, Familiar Social and Friends Support Scale, and Rosenberg Scale. Blood samples were biochemically analyzed. Analyses of variance were conducted between four groups according to symptom severity.Results: A considerable prevalence of stress, anxiety, and depression symptoms was observed and negatively correlated with self-esteem and socio-familiar support. Perceived stress was sexually dimorphic. Although biochemical parameters were within reference ranges, glutathione, CD4, and CD8 tended to be lower in participants with anxiety and depression symptoms, which may be of predictive value.Conclusion: The relationship between antioxidant/immune parameters and socio-affective scores is latent in undiagnosed college students who might develop affective disorders. The findings suggest that during the initial development of affective disorders, stress management strategies should be implemented to help college students cope with the academic load and monitor negative changes in their physiological state. (shrink)

Esta obra aborda el tema de la libertad, como el problema número uno de nuestro tiempo, junto al desarrollo.

Al hilo de los testimonios y las entrevistas, las biografías y el análisis de la obra de figuras cardinales como Isaiah Berlin, Jorge Luis Borges, Leszek Kolakowski, Hugh Thomas, Paul Kennedy o John Elliott, Travesía liberal ofrece las claves para comprender los vaivenes de la historia, desde la España imperial hasta el 11-S, y arrojar nueva luz en el inquietante comienzo del siglo xx. Sólo un historiador como Enrique Krauze podía vertebrar episodios tan alejados en el tiempo y en (...) la geografía como el movimiento neozapatista y el Holocausto, la Revolución de Terciopelo y el humanismo indigenista o el conflicto árabe-israelí... El rigor y la brillantez analítica que caracterizan las obras de Krauze confluyen en este volumen, en el que poco a poco se perfila no sólo la travesía de la humanidad a lo largo de los siglos, sino también la andadura intelectual del autor. (shrink)

This article examines the role of the Spanish Atomic Forum as the representative of the nuclear sector in the public arena during the golden years of the nuclear power industry from the 1960s to 1970s. It focuses on the public image concerns of the Spanish nuclear lobby and the subsequent information campaigns launched during the late 1970s to counteract demonstrations by the growing and heterogeneous anti-nuclear movement. The role of advocacy of nuclear energy by the Atomic Forum was similar to (...) that in other countries, but the situation in Spain had some distinguishing features. Anti-nuclear protest in Spain peaked in 1978 paralleling the debates of a new National Energy Plan in Congress, whose first draft had envisaged a massive nuclearization of the country. We show how the approval of the Plan in July 1979, with a significant reduction in the nuclear energy component, was influenced by the anti-nuclear protest movements in Spain. Despite the efforts of the Spanish Atomic Forum to counter its message, the anti-nuclear movement was strengthened by reactions to the Three Mile Island accident in March 1979. (shrink)

Advocates of interactionism in the ethical criticism of art argue that ethical value impacts aesthetic value. The debate is concerned with “the intrinsic question”: the question of whether ethical flaws/merits in artworks’ manifested attitudes affect their aesthetic value (Gaut 2007: 9). This paper argues that the assumption that artworks have intrinsic ethical value is problematic at least in regards to a significant subset of works: fictional artworks. I argue that, insofar as their ethical value emerges only from attitudes attributable to (...) actual agents, fictional artworks only have extrinsic ethical value. I show that what is at stake for interactionism is whether ethical judgements concerning artists’ attitudes in a context, rather than manifested attitudes, are ever aesthetically relevant. I conclude that, without buying into extreme actual intentionalism, a still controversial theory of interpretation that ties artworks’ meaning to actual artists, interactionism fails to show that ethical flaws/merits are aesthetic flaws/merits. (shrink)

Attempts to lay a foundation for the sciences based on modern mathematics are questioned. In particular, it is not clear that computer science should be based on set-theoretic mathematics. Set-theoretic mathematics has difficulties with its own foundations, making it reasonable to explore alternative foundations for the sciences. The role of computation within an alternative framework may prove to be of great potential in establishing a direction for the new field of computer science.Whitehead''s theory of reality is re-examined as a foundation (...) for the sciences. His theory does not simply attempt to add formal rigor to the sciences, but instead relies on the methods of the biological and social sciences to construct his world-view. Whitehead''s theory is a rich source of notions that are intended to explain every element of experience. It is a product of Whitehead''s earlier attempt to provide a mathematical foundation for the physical sciences and is still consistent with modern physics. (shrink)

Latin America is one of the most unequal continents in the world. This inequality translates into marked limitations in the possibilities of having a decent life for a high percentage of the population. Within the groups that are affected, women are undoubtedly even more so, because, in addition to shared economic and social inequalities with other vulnerable groups, they face discrimination based on gender. In Latin America, political protest has been undertaken by women who wish to denounce and abate the (...) injustices of which they are victims. These struggles have been analyzed by different thinkers. For the most part, feminist theories deal with the struggle of women against the oppressive behavior of patriarchy from the State or society. Others highlight the ability of women to contribute to social changes from socially accepted roles such as mothers, daughters, wives. These approaches ignore the difficulties experienced by female activists within the political mobilization. In this essay then we seek to document, analyze, and theorize about the patriarchal practices suffered by women activists - qua women- within the social organizations in Ciudad Juárez, as well as the forms of resistance they have opposed. (shrink)