Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.

A critical appraisal of the intrinsic pancreatic angiotensin-generating system

The pancreas is a relative newcomer to the stable of tissues with an intrinsic angiotensin-generating system. The involvement of this system in pancreatic activity will be dependent on the angiotensin-generating paths present in the pancreas and their precise cellular location. Thus far, renin, angiotensin-converting enzyme (ACE), angiotensin II and AT1 and AT2 receptors have been found. These are components of the "classical" renin-angiotensin system. But there is uncertainty as to their location and site of action. Furthermore, it is not known which, if any, alternative enzymes to renin and ACE are present, which angiotensins in addition to angiotensin II are generated and whether or not there are receptors to angiotensin IV and angiotensin-(1-7). Future research should focus on these aspects in order to provide a mechanistic basis to pancreatic physiological functions and to pathological conditions of clinical relevance.

Yehoshua Gitay: 'What is He Doing?'

This article provides a response to an article by Yehoshua Gitay, ‘Prophetic Criticism—"What are they Doing?": The Case of Isaiah—A Methodological Assessment’ (JSOT 96), in which he assesses the articles in the volume, New Visions of Isaiah. These articles were originally delivered as papers to the Formation of the Book of Isaiah Seminar of the Society of Biblical Literature. Gitay characterizes the entire work of the Seminar as having a redaction-critical focus. I argue that to characterize my article as representing a redaction-critical approach is to misunderstand what others and I were doing as participants in the Isaiah seminar. My article was in fact a critique of redaction criticism and its author-centred approach to textual meaning.

Detectives with pimples: how teen noir is crossing the frontiers of the traditional noir films

In the last ten years, teen noir movies and series — such as Donnie Darko (2001), Brick (2005), or Veronica Mars (2004-2007) — have become increasingly popular among audiences, both in the USA and in Europe, and aroused the curiosity of critics. These teen noir adventures present darker themes and technical features that distinguish them from numerous productions aiming at young adults. Their narrative and aesthetic characteristics reinvent and subvert the tradition of classic noir movies of the forties and fifties, thus generating a sense of novelty. In this article, I focus my attention on Veronica Mars, a famous teen noir series, created by Rob Thomas, to examine: a) the teen noir themes; b) the new profile and role of the private investigator; c) the empowerment of girls/young women; d) razor-sharp dialogues; e) intertextual references to old- school noir movies. In order to do so, resort to the research of specialists in the field of neo noir, such as Mark Conrad, Foster Hirsch, or Roz Kaveney. My main goal is to prove that a new (sub)genre is slowly emerging and revivifying teen cinema.

Contributo da radioterapia na melhoria dos cuidados de saúde no Centro Nacional de Oncologia - Luanda

Mestrado em Radiações Aplicadas às Tecnologias da Saúde - Área de especialização: Terapia com Radiações

The visual image in Epiphanic Short History

The visual image is a fundamental component of epiphany, stressing its immediacy and vividness, corresponding to the enargeia of the traditional ekphrasis and also playing with cultural and social meanings. Morris Beja in his seminal book Epiphany in the Modern Novel, draws our attention to the distinction made by Joyce between the epiphany originated in a common object, in a discourse or gesture and the one arising in “a memorable phase of the mind itself”. This type materializes in the “dream-epiphany” and in the epiphany based in memory. On the other hand, Robert Langbaum in his study of the epiphanic mode, suggests that the category of “visionary epiphany” could account for the modern effect of an internally glowing vision like Blake’s “The Tyger”, which projects the vitality of a real tyger. The short story, whose length renders it a fitting genre for the use of different types of epiphany, has dealt with the impact of the visual image in this technique, to convey different effects and different aesthetic aims. This paper will present some examples of this occurrence in short stories of authors in whose work epiphany is a fundamental concept and literary technique: Walter Pater, Joseph Conrad, K. Mansfield, Clarice Lispector. Pater’s “imaginary portraits” concentrate on “priviledged moments” of the lives of the characters depicting their impressions through pictorial language; Conrad tries to show “moments of awakening” that can be remembered by the eye; Mansfield suggests that epiphany, the “glimpse”, should replace plot as an internal ordering principle of her impressionist short-stories; in C. Lispector the visualization of some situations is so aggressive that it causes nausea and a radical revelation on the protagonist’s.

Do tempo absoluto ao tempo 5D eonico

A questão do tempo é tão antiga como a Filosofia. Ela surge já nos pre-socráticos intimamente associada à relação ontológica fundamental Ser/Devir, é retomada dentro da filosofia platônica principalmente no "Timeu" e posteriormente na "Física" de Aristóteles. Agostinho de Hipona e Tomás de Aquino não deixam também de reflectir sobre o tempo, sendo a contribuição do primeiro tão notável que ainda continua a influenciar o pensamento contemporâneo. O espírito da modernidade, sob a influência de Galileu, Descartes e Newton retoma a questão propondo um tempo abstracto, matemático e mecanicista que passou a designar-se por Tempo Absoluto e dominou o pensamento ocidental por cerca de duzentos anos. Porém, este tempo é um tempo reversível totalmente inadequado às ciências da vida que foram surgindo durante o Sec.XIX. A Teoria da Relatividade recusa o Tempo Absoluto e propõe um Tempo Relativo, mas este ainda é reversível. A Biologia e a Sistêmica contemporâneas, além da Mecânica Estatística, insistem numa Flecha do Tempo sem a qual os fenômenos essenciais da ciência de hoje seriam inexplicáveis. É neste quadro de reflexão que a proposta do super-tempo eónico feita pela ontóloga e fenomenôloga Hedwig Conrad-Martius, de Munique, tem o maior interesse.

The effectiveness of supply chain management on firm's performance: A comparative case study

The purpose of the paper is to investigate the effectiveness of supply chain management (SCM) practices to increase a company’s performance based on a cross-border and cross-sector analysis. The paper follows a comparative case study approach which was achieved by interviewing supply chain management experts of three companies operating in different industries and positions in a supply chain. Practices that were mutually applied by the firms and their contribution to achieve quality, economic, cost, and time advantages were analyzed. The paper revealed practices, which contribute the most to increase specific performance areas.

Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca

OBJETIVO: Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR). MÉTODOS: Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC) e sem falência cardíaca (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contrações isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ºC). RESULTADOS: Os valores da tensão máxima desenvolvida (TD) e da velocidade máxima de encurtamento (Vmáx) foram menores nos SHR-IC e SHR, em relação aos WKY (p<0,05). TD e Vmáx foram semelhantes nos SHR-IC e SHR (p>0,05). A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p<0,05 vs WKY e SHR); esta variável não diferiu entre WKY e SHR (p>0,05). CONCLUSÃO: Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associada ao aumento da rigidez passiva do miocárdio e não à piora da função contrátil do músculo cardíaco.

Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb. 2016.00275

Nova genera plantarum...

pt.1-2 1781-82

Nova genera plantarum...

pt.3, 5 1783-84