Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation.

The DNA-damage checkpoint kinase Chk1 is essential in higher eukaryotes due to its role in maintaining genome stability in proliferating cells. CHK1 gene deletion is embryonically lethal, and Chk1 inhibition in replicating cells causes cell-cycle defects that eventually lead to perturbed replication and replication-fork collapse, thus generating endogenous DNA damage. What is the cause of replication-fork collapse when Chk1 is inactivated, however, remains poorly understood. Here, we show that generation of DNA double-strand breaks at replication forks when Chk1 activity is compromised relies on the DNA endonuclease complex Mus81/Eme1. Importantly, we show that Mus81/Eme1-dependent DNA damage--rather than a global increase in replication-fork stalling--is the cause of incomplete replication in Chk1-deficient cells. Consequently, Mus81/Eme1 depletion alleviates the S-phase progression defects associated with Chk1 deficiency, thereby increasing cell survival. Chk1-mediated protection of replication forks from Mus81/Eme1 even under otherwise unchallenged conditions is therefore vital to prevent uncontrolled fork collapse and ensure proper S-phase progression in human cells

Zeros, chaotic ratios and the computational complexity of approximating the independence polynomial

The independence polynomial originates in statistical physics as the partition function of the hard-core model. The location of the complex zeros of the polynomial is related to phase transitions, and plays an important role in the design of efficient algorithms to approximately compute evaluations of the polynomial.In this paper we directly relate the location of the complex zeros of the independence polynomial to computational hardness of approximating evaluations of the independence polynomial. We do this by moreover relating the location of zeros to chaotic behaviour of a naturally associated family of rational functions; the occupation ratios

A Reilly formula and eigenvalue estimates for differential forms

We derive a Reilly-type formula for differential p-forms on a compact manifold with boundary and apply it to give a sharp lower bound of the spectrum of the Hodge Laplacian acting on differential forms of an embedded hypersurface of a Riemannian manifold. The equality case of our inequality gives rise to a number of rigidity results, when the geometry of the boundary has special properties and the domain is non-negatively curved. Finally we also obtain, as a by-product of our calculations, an upper bound of the first eigenvalue of the Hodge Laplacian when the ambient manifold supports non-trivial parallel forms.Comment: 22 page

Age-related changes of the ocular surface : a hospital setting-based retrospective study

Purpose. To investigate the effects of age on the prevalence of ocular surface diseases (OSD), adherence to treatment, and recovery rates. Patients and Methods. Retrospective analysis of 3000 clinical records from a first-level general ophthalmology clinic. Patients with OSD were prospectively submitted a questionnaire to assess compliance and recovery rates. Results. OSD prevalence was 10.3%. Patients with OSD were significantly older than patients without it: 67.5 \ub1 20.3 versus 57.0 \ub1 22.0 years (P = 0.036). No significant difference in season distribution was shown. Dry eye disease (DED) represented 58% of OSD; its prevalence increased with age until 80 years old and suddenly decreased thereafter. Asymptomatic DED was 37%. Adherence to treatment in OSD was very high (94%); recovery rates were lower in patients aged 21-40 and 61-80 (resp., 65.5% and 77.8%) and this was associated with higher OSDI scores. Tear substitutes represented 50% of all prescribed medications; their use increased with age. Discussion. In a "reallife"low-tech setting, OSD showed a prevalence of 10.3%. DED was the most prevalent disease, and it was asymptomatic in more than 1/3 of cases

Lee-Yang Zeros of the antiferromagnetic Ising Model

We investigate the location of zeros for the partition function of the anti-ferromagnetic Ising Model, focusing on the zeros lying on the unit circle. We give a precise characterization for the class of rooted Cayley trees, showing that the zeros are nowhere dense on the most interesting circular arcs. In contrast, we prove that when considering all graphs with a given degree bound, the zeros are dense in a circular sub-arc, implying that Cayley trees are in this sense not extremal. The proofs rely on describing the rational dynamical systems arising when considering ratios of partition functions on recursively defined trees

Palavra de tradutor: reflexões sobre tradução por tradutores brasileiros / The Translator's Word: Reflections on Translation by Brazilian translators

Este livro reúne reflexões acerca de concepções de tradução e do fazer tradutório a partir do ponto de vista de diferentes tradutores brasileiros. São reflexões não sistematizadas, produzidas em momentos históricos diferentes, que cobrem um arco temporal de mais de duzentos anos, do final do século XVIII até os nossos dias. São paratextos e metatextos escritos por tradutores, homens e mulheres, que emolduram abordagens de gêneros textuais diversos: do texto técnico-científico ao de ficção, passando pela literatura infantojuvenil, pela poesia épica e lírica e pelo drama.This book brings together reflections on translation and its practice from the viewpoints of a variety of Brazilian translators. These are non-systematized reflections which were produced in different historical contexts spanning over two hundred years, from the end of the 18th century until the present day. They come from paratexts and meta-texts written by translators, men and women, which offer approaches to diverse textual genres: from technical/scientific writings to fiction, as well as children’s literature, epic and lyrical poetry, and drama

Superposed sedimentary and tectonic block-in-matrix fabrics in a subducted serpentinite m\ue9lange (High-pressure zermatt saas ophiolite, western alps)

The primary stratigraphic fabric of a chaotic rock unit in the Zermatt Saas ophiolite of the Western Alps was reworked by a polyphase Alpine tectonic deformation. Multiscalar structural criteria demonstrate that this unit was deformed by two ductile subduction-related phases followed by brittle-ductile then brittle deformation. Deformation partitioning operated at various scales, leaving relatively unstrained rock domains preserving internal texture, organization, and composition. During subduction, ductile deformation involved stretching, boudinage, and simultaneous folding of the primary stratigraphic succession. This deformation is particularly well-documented in alternating layers showing contrasting deformation style, such as carbonate-rich rocks and turbiditic serpentinite metasandstones. During collision and exhumation, deformation enhanced the boudinaged horizons and blocks, giving rise to spherical to lozenge-shaped blocks embedded in a carbonate-rich matrix. Structural criteria allow the recognition of two main domains within the chaotic rock unit, one attributable to original broken formations reflecting turbiditic sedimentation, the other ascribable to an original sedimentary m\ue9lange. The envisaged geodynamic setting for the formation of the protoliths is the Jurassic Ligurian-Piedmont ocean basin floored by mostly serpentinized peridotites, intensely tectonized by extensional faults that triggered mass transport processes and turbiditic sedimentation

T Cell Therapy for Nasopharyngeal Carcinoma

Among the novel biologic therapeutics that will increase our ability to cure human cancer in the years to come, T cell therapy is one of the most promising approaches. However, with the possible exception of tumor-infiltrating lymphocytes therapy for melanoma, clinical trials of adoptive T-cell therapy for solid tumors have so far provided only clear proofs-of-principle to build on with further development. Epstein-Barr virus (EBV)-associated malignancies offer a unique model to develop T cell-based immune therapies, targeting viral antigens expressed on tumor cells. In the last two decades, EBV-specific cytotoxic T-lymphocytes (CTL) have been successfully employed for the prophylaxis and treatment of EBV-related lymphoproliferative disorders in immunocompromised hosts. More recently, this therapeutic approach has been applied to the setting of EBV-related solid tumors, such as nasopharyngeal carcinoma. The results are encouraging, although further improvements to the clinical protocols are clearly necessary to increase anti-tumor activity. Promising implementations are underway, including harnessing the therapeutic potential of CTLs specific for subdominant EBV latent cycle epitopes, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells