Reología de mezclas de cemento con filler dolomítico

This experimental program has studied the behavior of fresh paste made up from cements mixed with dolomite filler. Through prior experiments the starting point is obtained for the designs 22 and 23 factorials. With these designs the governing equations are established that influence the specific surface of the filler, the filler percentage and the ratio water/(cement + filler), used as objective functions: test probe penetration, flow on table and shear stress in viscometer. Also the type of rheological conduct is determined and the influence over initial and final setting is observed.Este programa experimental estudia el comportamiento de las pastas frescas fabricadas a partir de cementos mezclados con filler dolomítico. En los experimentos previos se obtiene el punto central para los diseños 22 y 23 factoriales. Con estos diseños se establecen las ecuaciones que rigen la influencia de la superficie específica del filler, el porcentaje de filler y la relación agua/(cemento + filler), utilizando como funciones objetivos la penetración de sonda, la mesa de sacudidas y la tensión de corte en el viscosímetro. También se determina el tipo de conducta reológica y la influencia sobre el principio y fin de fraguado

Root Suberin Forms an Extracellular Barrier That Affects Water Relations and Mineral Nutrition in Arabidopsis

Though central to our understanding of how roots perform their vital function of scavenging water and solutes from the soil, no direct genetic evidence currently exists to support the foundational model that suberin acts to form a chemical barrier limiting the extracellular, or apoplastic, transport of water and solutes in plant roots. Using the newly characterized enhanced suberin1 (esb1) mutant, we established a connection in Arabidopsis thaliana between suberin in the root and both water movement through the plant and solute accumulation in the shoot. Esb1 mutants, characterized by increased root suberin, were found to have reduced day time transpiration rates and increased water-use efficiency during their vegetative growth period. Furthermore, these changes in suberin and water transport were associated with decreases in the accumulation of Ca, Mn, and Zn and increases in the accumulation of Na, S, K, As, Se, and Mo in the shoot. Here, we present direct genetic evidence establishing that suberin in the roots plays a critical role in controlling both water and mineral ion uptake and transport to the leaves. The changes observed in the elemental accumulation in leaves are also interpreted as evidence that a significant component of the radial root transport of Ca, Mn, and Zn occurs in the apoplast

Medico-legal reasoning in disability assessment: A focus group and validation study

<p>Abstract</p> <p>Background</p> <p>Decisions on disability pensions are based, among others, on medical reports. The way these medical assessments are performed is largely unclear. The aim of the study was to determine which grounds are used by social insurance physicians (SIPs) in these assessments and to determine if the identification of these grounds can help improve the quality of assessments in social insurance practice. The article describes a focus group study and a questionnaire study with SIPs in four different countries.</p> <p>Method</p> <p>Using focus group discussions of SIPs discussing the same case in Belgium, the Netherlands, Norway and Slovenia (N = 29) we determined the arguments and underlying grounds as used by the SIP's. We used a questionnaire study among other SIPs (N = 60) in the same countries to establish a first validation of these grounds.</p> <p>Results</p> <p>Grounds in the focus groups were comparable between the countries studied. The grounds were also recognized by SIPs who had not participated in the focus groups. SIPs agreed most on grounds with regard to the claimant's health condition, and about the claimant's duty to explore rehabilitation and work resumption, but less on accepting permanent incapacity when all options for treatment were exhausted.</p> <p>Conclusion</p> <p>Grounds that SIPs use refer to a limited group of key elements of disability evaluation. SIPs interpret disability in social insurance according to the handicapped role and strive at making their evaluation fair trials. ICF is relevant with regard to the health condition and to the process of evaluation. Identification of grounds is a valuable instrument for controlling the quality of disability evaluation. The grounds also appear to be internationally comparable which may enhance scientific study in this area.</p

Of Mice and Measures : A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic.

A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies

Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne

Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients

Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

BACKGROUND: Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. METHODS: Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. RESULTS: Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. CONCLUSIONS: These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

Rudra Interrupts Receptor Signaling Complexes to Negatively Regulate the IMD Pathway

Insects rely primarily on innate immune responses to fight pathogens. In Drosophila, antimicrobial peptides are key contributors to host defense. Antimicrobial peptide gene expression is regulated by the IMD and Toll pathways. Bacterial peptidoglycans trigger these pathways, through recognition by peptidoglycan recognition proteins (PGRPs). DAP-type peptidoglycan triggers the IMD pathway via PGRP-LC and PGRP-LE, while lysine-type peptidoglycan is an agonist for the Toll pathway through PGRP-SA and PGRP-SD. Recent work has shown that the intensity and duration of the immune responses initiating with these receptors is tightly regulated at multiple levels, by a series of negative regulators. Through two-hybrid screening with PGRP-LC, we identified Rudra, a new regulator of the IMD pathway, and demonstrate that it is a critical feedback inhibitor of peptidoglycan receptor signaling. Following stimulation of the IMD pathway, rudra expression was rapidly induced. In cells, RNAi targeting of rudra caused a marked up-regulation of antimicrobial peptide gene expression. rudra mutant flies also hyper-activated antimicrobial peptide genes and were more resistant to infection with the insect pathogen Erwinia carotovora carotovora. Molecularly, Rudra was found to bind and interfere with both PGRP-LC and PGRP-LE, disrupting their signaling complex. These results show that Rudra is a critical component in a negative feedback loop, whereby immune-induced gene expression rapidly produces a potent inhibitor that binds and inhibits pattern recognition receptors