Local vs. global pragmatics

In 'Local pragmatics in a Gricean framework', Mandy Simons argues that, contrary to the received view, it is possible to accommodate local pragmatic effects utilising just the mechanisms for pragmatic reasoning provided by Grice. Although I agree with this overarching claim, this paper argues that we need to be careful in our understanding of 'what is said', and the nature of communicated content in general, when deciding between local and global accounts of pragmatic effects.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Immobilized Kidney 28-kDa Endostatin- Related (KES28kDa) Fragment Promotes Endothelial Cell Survival

Background/Objective: Renal ischemia-hypoxia is a leading cause of acute kidney injury (AKI). Ischemia causes extracellular matrix breakdown of the tubular basement membrane. Endostatin (ES) is the C-terminal fragment of collagen XVIII generated by proteolytic cleavage. Recent studies have demonstrated that ES expression is upregulated in ischemic kidneys. The present study aimed to characterize ES from ischemic kidneys. Methods: Ischemic renal failure was induced via 45 min of occlusion of the left renal artery and vein. After the ischemic period, blood was collected. Kidneys were harvested and used for immunohistochemical testing and protein extraction. Three-step purification was used. Soluble and immobilized purified ES were tested in cell viability and adhesion assays. Results: The soluble KES28kDa inhibited endothelial cell proliferation: 25 versus 12.5 mu g (p < 0.05); 12.5 versus 3.15 mu g (p < 0.05). Immobilization of KES28kDa supports endothelial cell survival over the control p = 0.021). Human umbilical vein endothelial cells plated on immobilized KES28kDa showed an increase in membrane ruffles and stress fibers. Conclusion: These data demonstrate the local synthesis of a 28-kDa ES-related fragment following AKI and suggest its role in endothelium survival. Copyright (C) 2010 S. Karger AG, Basel

Total absolute horospherical curvature of submanifolds in hyperbolic space

We study the horospherical geometry of submanifolds in hyperbolic space. The main result is a formula for the total absolute horospherical curvature of M, which implies, for the horospherical geometry, the analogues of classical inequalities of the Euclidean Geometry. We prove the horospherical Chern-Lashof inequality for surfaces in 3-space and the horospherical Fenchel and Fary-Milnor`s theorems.

TAUT REPRESENTATIONS OF COMPACT SIMPLE LIE GROUPS

The concept of taut submanifold of Euclidean space is due to Carter and West, and can be traced back to the work of Chern and Lashof on immersions with minimal total absolute curvature and the subsequent reformulation of that work by Kuiper in terms of critical point theory. In this paper, we classify the reducible representations of compact simple Lie groups, all of whose orbits are tautly embedded in Euclidean space, with respect to Z(2)-coefficients.

A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system

The aim of this study was to evaluate the anti-tumor activity of Amblyomin-X, a serine protease Kunitz-type inhibitor. Amblyomin-X induced tumor mass regression and decreased number of metastatic events in a B16F10 murine melanoma model. Alterations on expression of several genes related to cell cycle were observed when two tumor cell lines were treated with Amblyomin-X. PSMB2, which encodes a proteasome subunit, was differentially expressed, in agreement to inhibition of proteasomal activity in both cell lines. In conclusion, our results indicate that Amblyomin-X selectively acts on tumor cells by inducing apoptotic cell death, possibly by targeting the ubiquitin-proteasome system. (C) 2010 Elsevier Ltd. All rights reserved.

A conversão de D. José Brandão de Castro : a ação social de mediadores religiosos na Diocese de Propriá

This dissertation looked for to study the charisma of the religious mediator us " Movements of Christianity of Liberation " in the Diocese Sergipana of Propriá, during the decade from sixty to eighty. Centering our debate in the understanding of the social action, we have as main subject to understand the " poor " influence in the adoption of actions on the part of the mediators, in that public's favor, mainly in Fazenda Betume conflicts (1974) and of Santana dos Frades (1979). The hypotheses, we became pregnant that the mediators as D. José Brandão de Castro and the nun Maria Joana Hermínia exercised an important influence in the construction of the identity of the movements as CEBs, MEB and CPT in the area. Such influence was motivated by a conversion of the mediator D. Brandão, constituted starting from a relationship maintained between him and the members of the movements and proportionate for the critics and demands done by the popular ones. They resulted in actions in favor of the rural ones, what characterized the Church of Propriá as allied of the involved in the conflicts and no mere middleman. Before the collected material, we made use of the Analysis of Content using the poor " term " as analysis category, complemented by interviews done to members of the mentioned movements. Esta dissertação buscou estudar o carisma do mediador religioso nos “Movimentos de Cristianismo de Libertação” na Diocese Sergipana de Propriá, durante a década de sessenta a oitenta. Centrando nosso debate na compreensão da ação social, temos como questão principal entender a influência dos “pobres” na adoção de ações por parte do mediador, em favor desse público, principalmente nos conflitos da Fazenda Betume (1974) e de Santana dos Frades (1979). Como hipóteses, concebemos que os mediadores como D. José Brandão de Castro e a freira Maria Joana Hermínia exerceram uma importante influência na construção da identidade dos movimentos como as CEBs, o MEB e a CPT na região. Tal influência foi motivada por uma conversão do mediador D. Brandão, constituída a partir de uma relação mantida entre ele e os membros dos movimentos e proporcionada pelas críticas e demandas feita pelos populares. Elas resultaram em ações em favor dos campesinos, o que caracterizou a Igreja de Propriá como aliada dos envolvidos nos conflitos e não mera intermediária. Ante o material coletado, fizemos uso da Análise de Conteúdo utilizando o termo “pobre” como categoria de análise, complementada por entrevistas feitas à membros dos movimentos citados.

The last five amino acid residues at the C-terminus of PRK1 /KKN is essential for full lipid responsiveness

PRK1/PKN is a member of the protein kinase C (PKC) superfamily of serine/threonine protein kinases. Despite its important role as a RhoA effector, limited information is available regarding how this kinase is regulated. We show here that the last seven amino acid residues at the C-terminus is dispensable for the catalytic activity of PRK1 but is critical for the in vivo stability of this kinase. Surprisingly, the intact hydrophobic motif in PRK1 is dispensable for 3-phosphoinositide-dependent kinase-1 (PDK-1) binding and phosphorylation of the activation loop, as the PRK1-&Delta;940 mutant lacking the last two residues of the hydrophobic motif and the last 5 residues at the C-terminus interacts with PDK-1 in vivo and has a similar specific activity as the wild-type protein. We also found that the last four amino acid residues at the C-terminus of PRK1 is critical for the full lipid responsiveness as the PRK1-&Delta;942 deletion mutant is no longer activated by arachidonic acid. Our data suggest that the very C-terminus in PRK1 is critically involved in the control of the catalytic activity and activation by lipids. Since this very C-terminal segment is the least conserved among members of the PKC superfamily, it would be a promising target for isozyme-specific pharmaceutical interventions.