The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Um estudo sobre a teoria de campos no espaço-tempo não comutativo

Os aspectos quânticos de teorias de campo formuladas no espaço-tempo não comutativo têm sido amplamente estudados ao longo dos anos. Um dos principais aspectos é o que na literatura ficou conhecido como mixing IR/UV. Trata-se de uma mistura das divergências, que foi vista pela primeira vez no trabalho de Minwalla et al [28], onde num estudo do campo escalar não comutativo com interação quártica vemos já a 1 loop que o tadpole tem uma divergência UV associada a sua parte planar e, junto com ela, temos uma divergência IR associada com um gráfico não planar. Essa mistura torna a teoria não renormalizável. Dado tal problema, houve então uma busca por mecanismos que separassem essas divergências a fim de termos teorias renormalizáveis. Um mecanismo proposto foi a adição de um termo não local na ação U*(1) para que esta seja estável.Neste trabalho, estudamos através da renormalização algébrica a estabilidade deste modelo. Para tal, precisamos localizar o operador não local através de campos auxiliares e seus respectivos ghosts (metodo de Zwanziger) na intenção de retirar os graus de liberdade indesejados que surgem. Usamos o approachda quebra soft de BRST para analisar o termo que quebra BRST, que consiste em reescrevermos tal termo com o auxílio de fontes externas que num determinado limite físico voltam ao termo original.Como resultado, vimos que a teoria com a adição deste termo na ação só é renormalizável se tivermos que introduzir novos termos, sendo alguns deles quárticos. Porém, estes termos mudam a forma do propagador, que não desacopla as divergências. Um outro aspecto que podemos salientar é que, dependendo da escolha de alguns parâmetros, o propagador dá indícios de termos um fótonconfinante, seguindo o critério de Wilson e o critério da perda da positividade do propagador.

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

A novel brain partition highlights the modular skeleton shared by structure and function

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.

Ode marítima: leitura de Álvaro de Campos

A presente dissertação é fruto da pesquisa de mestrado realizada sobre o poema Ode marítima, de Álvaro de Campos, heterônimo do poeta português Fernando Pessoa. O poema foi estudado à luz de considerações teóricas que pudessem sustentar o teor artístico do citado poema, para além de um posicionamento estritamente analítico. Em outras palavras, as contribuições teóricas de Walter Benjamin, Philippe Lacoue-Labarthe, Theodor W. Adorno, entre outros, visa propocionar um discurso de pesquisa que seja poético, respeitando a manifestação literária em questão o poema. Nesse sentido, Ode marítima apresentou, ao longo da pesquisa, diferentes temas. Tais temas foram estudados, com o embasamento teórico referido, separadamente. São eles: Imaginação, Cais Absoluto, Sonho, Força e Infância. Para cada tema, um capítulo foi elaborado. Todos os temas pesquisados confluem para a apreensão da poética de Álvaro de Campos uma vez que Ode marítima é um poema singular e fundamental da obra poética do citado heterônimo. Desse modo, a pesquisa realizada não se limita à abordagem do citado poema, mas alcança demais poemas de Álvaro de Campos, de modo que se torna possível conjeturar acerca da poesia deste heterônimo. Partindo, portanto, de um poema, a pesquisa pretende poder dimensionar a obra de Álvaro de Campos, pontuando suas particularidades trazidas pela Ode marítima, mas tendo ciência de que trata-se de uma proposta entre tantas outras válidas e enriquecedoras.

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids.

Feeding habits of European hake (Merluccius merluccius) in the central Mediterranean Sea

European hake (Merluccius merluccius) is an important predator of deeper shelf-upper slope Mediterranean communities. It is a nectobenthic species distributed over a wide depth range (20−1000 m) throughout the Mediterranean Sea and the north east Atlantic region (Fisher et al., 1987). Notwithstanding the ecological and economic importance (Oliver and Massutí, 1995) of hake in the Mediterranean, many aspects of its biology (e.g., recruitment and reproduction), due to multiple spawning (Sarano, 1986) and the current state of exploitation, are poorly understood (Arneri and Morales-Nin, 2000).

Kent estuary survey 18th August 1981

This is the Kent estuary survey 18th July 1981 produced by the North West Water Authority in 1981. The report focuses on a tidal cycle survey carried out on the Kent estuary on the 18th August, 1981. The chemical water quality at Arnside Pier and at New Barns was, on the whole, acceptable. However, samples taken downstream of the outfall at low water for total coliforms and E. coli were all above the EEC mandatory level whilst those for faecal streptococci were all above the guideline value. This document shows chemical and bacteriological data analysed at Kent estuary such chloride, dissolved oxygen, BOD, ammonia, nitrate, phosphate, total coliforms, E. coli and Faecal streptococci.

BRST: da quebra suave à quebra espontânea da simetria

Nesta tese falamos essencialmente sobre a simetria BRST no modelo de Gribov-Zwanziger. Estudamos a quebra suave, a quebra linear e a quebra espontânea, todas da simetria BRST. Na formulação padrão do modelo, quebrada suavemente, construímos o modelo de réplica usado para estimar os valores das massas das glueballs. Utilizando campos auxiliares construímos um modelo quebrado linearmente, e utilizando basicamente o mesmo procedimento, uma formulação mais recente onde a simetria é quebrada espontâneamente.

Global nonlinear dynamics of thin aerofoil wakes

In the present investigation of thin aerofoil wakes we compare the global nonlinear dynamics, obtained by direct numerical simulations, to the associated local instability features, derived from linear stability analyses. A given configuration depends on two control parameters: the Reynolds number Re and the adverse pressure gradient m (with m < 0) prevailing at the aerofoil trailing edge. Global instability is found to occur for large enough Re and |m|; the naturally selected frequency is determined by the local absolute frequency prevailing at the trailing edge. © 2010 Springer Science+Business Media B.V.

Dynamic models of piled foundations

The vibration behavior of piled foundations is an important consideration in fields such as earthquake engineering, construction, machine-foundation design, offshore structures, nuclear energy, and road and rail development. This paper presents a review of the past 40 years' literature on modeling the frequency-dependent behavior of pile foundations. Beginning with the earliest model of a single pile, adapted from those for embedded footings, it charts the development of the four pile-modeling techniques: the "dynamic Winkler-foundation" approach that uses springs to represent the effect of the soil; elasticcontinuum-type formulations involving the analytical solutions for displacements due to a subsurface disk, cylinder, or other element; boundary element methods; and dynamic finite-element formulations with special nonreflecting boundaries. The modeling of pile groups involves accounting for pile-soil-pile interactions, and four such methods exist: interaction factors; complete pile models; the equivalent pier method; and periodic structure theory. Approaches for validating pile models are also explored. Copyright © 2013 by ASME.

Global modes with multiple saddle points

Significant progress has been made towards understanding the global stability of slowly-developing shear flows. The WKBJ theory developed by Patrick Huerre and his co-authors has proved absolutely central, with the result that both the linear and the nonlinear stability of a wide range of flows can now be understood in terms of their local absolute/convective instability properties. In many situations, the local absolute frequency possesses a single dominant saddle point in complex X-space (where X is the slow streamwise coordinate of the base flow), which then acts as a single wavemaker driving the entire global linear dynamics. In this paper we consider the more complicated case in which multiple saddles may act as the wavemaker for different values of some control parameter. We derive a frequency selection criterion in the general case, which is then validated against numerical results for the linearized third-order Ginzburg-Landau equation (which possesses two saddle points). We believe that this theory may be relevant to a number of flows, including the boundary layer on a rotating disk and the eccentric Taylor-Couette-Poiseuille flow. © 2014 Elsevier Masson SAS. All rights reserved.

Climate change, sea level rise and integrated coastal zone management: An IPCC approach

Expansion of economic activities, urbanisation, increased resource use and population growth are continuously increasing the vulnerability of the coastal zone. This vulnerability is now further raised by the threat of climate change and accelerated sea level rise. The potentially severe impacts force policy-makers to also consider long-term planning for climate change and sea level rise. For reasons of efficiency and effectiveness this long-term planning should be integrated with existing short-term plans, thus creating an Integrated Coastal Zone Management programme. As a starting point for coastal zone management, the assessment of a country's or region's vulnerability to accelerated sea level rise is of utmost importance. The Intergovernmental Panel on Climate Change has developed a common methodology for this purpose. Studies carried out according to this Common Methodology have been compared and combined, from which general conclusions on local, regional and global vulnerability have been drawn, the latter in the form of a Global Vulnerability Assessment. In order to address the challenge of coping with climate change and accelerated sea level rise, it is essential to foresee the possible impacts, and to take precautionary action. Because of the long lead times needed for creating the required technical and institutional infrastructures, such action should be taken in the short term. Furthermore, it should be part of a broader coastal zone management and planning context. This will require a holistic view, shared by the different institutional levels that exist, along which different needs and interests should be balanced.

长江口水文、泥沙过程与圆桩冲刷的数值模拟

本文主要利用ECOMSED模式对长江口及邻近海域的水文、泥沙过程进行三维数值模拟，并结合实测资料分析其水动力、泥沙输运、底床冲淤等特征；然后利用欧拉二相流模型模拟小尺度条件下长江口底床上圆桩周围的水流和泥沙冲刷、输运规律。 通过资料分析和ECOMSED数值模拟结果比较，我们得出：长江口口门内为非正规半日潮流区，潮流运动形式多为往复流，落潮流占优。落潮流速大于涨潮流速，流速垂向分布从表层到底层递减。悬沙浓度与流速关系密切，一般来说，流速越大，悬沙浓度越高；一个潮周期过程中会出现两次、三次或四次泥沙再悬浮，分别是涨急、落急、涨转落、落转涨时刻；盐水楔结构对粘性与非粘性悬沙浓度的分布起决定性作用，转流时泥沙再悬浮主要是由于这时会出现盐水楔，并形成垂向环流，使床面大量未被固结的泥沙再悬浮，形成峰值。悬浮泥沙垂向分布可分为垂线型，斜线型，抛物线型和L型。流场和底床冲淤变化与水深关系密切：深水区，流速较大，底床冲淤变化也较大。其中，受径流影响区表现为淤积，受潮流影响区表现为冲刷；浅水区基本表现为淤积。 从模式运行结果和实测资料比较可以看出，该模型可以较好的模拟长江口水流、悬浮泥沙分布与变化；能够再现在径流入海口处，盐水楔结构及其诱生的垂向环流从形成到发展，又到消失的完整过程；也能够展示底床的冲淤变化。对于我们模拟长江口背景流场，了解该区域内水动力变化、悬浮泥沙输运、底床冲淤等有重要意义。 在欧拉二相流模型对长江口底床上圆桩周围的水流和局部冲刷数值模拟过程中，我们不仅考虑水流和泥沙之间的作用，还引入泥沙颗粒之间的相互影响。模拟结果较合理的展示了圆桩周围的流场类型和底床冲刷变化：在圆桩前方，流速减小并形成垂向涡旋，从而产生局部冲刷；在圆桩两侧，水流加速，挟带上游泥沙向下输送，并在内侧堆积；而在圆桩后面，存在流速分离区。在该分离区内流速很小，并且当流速较大时，会产生回流，形成两个对称的漩涡。流速越大，圆桩前由垂向涡旋引起的局部冲刷就越明显；而当底床泥沙粒径变小时，泥沙临界起动流速变小，底床也更容易被冲刷。悬浮泥沙浓度分布受流场的影响，并且当粒径小而流速大时，能悬浮到更高的深度。