Exploration of the cell-cycle genes found within the RIKEN FANTOM2 data set

The cell cycle is one of the most fundamental processes within a cell. Phase-dependent expression and cell-cycle checkpoints require a high level of control. A large number of genes with varying functions and modes of action are responsible for this biology. In a targeted exploration of the FANTOM2-Variable Protein Set, a number of mouse homologs to known cell-cycle regulators as well as novel members of cell-cycle families were identified. Focusing on two prototype cell-cycle families, the cyclins and the NIMA-related kinases (NEKs), we believe we have identified all of the mouse members of these families, 24 cyclins and 10 NEKs, and mapped them to ENSEMBL transcripts. To attempt to globally identify all potential cell cycle-related genes within mouse, the MGI (Mouse Genome Database) assignments for the RIKEN Representative Set (RPS) and the results from two homology-based queries were merged. We identified 1415 genes with possible cell-cycle roles, and 1758 potential paralogs. We comment on the genes identified in this screen and evaluate the merits of each approach.

OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

Background: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization. Objective: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization. Methods: Data driven approach: (1) Two databases were considered The 'elaboration' database with which the formal OARSI sets of responder criteria were elaborated and The 'revisit' database. (2) Six different scenarios were evaluated: The two formal OARSI sets of criteria Four proposed scenarios of simplified sets of criteria Data from clinical randomized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different databases ('elaboration' versus 'revisit') and those of the four proposed simplified scenarios within the 'revisit' database. The placebo effect, active effect, treatment effect, and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios. Experts' opinion approach: Results were discussed among the participants of the OMERACT VI meeting, who voted to select the definite OMERACT-OARSI set of criteria (one of the six evaluated scenarios). Results: Data driven approach: Fourteen trials totaling 1886 CA patients and fifteen studies involving 8164 CA patients were evaluated in the 'elaboration' and the 'revisit' databases respectively. The variability of the performances observed in the 'revisit' database when using the different simplified scenarios was similar to that observed between the two databases ('elaboration' versus 'revisit') when using the formal scenarios. The treatment effect and the required sample arm size were similar for each set of criteria. Experts' opinion approach: According to the experts, these two previous performances were the most important of an optimal set of responder criteria. They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response, with similar cut-offs whatever the drug, the route of administration or the CA localization. Conclusion: This data driven and experts' opinion approach is the basis for proposing an optimal simplified set of responder criteria for CA clinical trials. Other studies, using other sets of CA patients, are required in order to further validate this proposed OMERACT - OARSI set of criteria. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Single- vs. multiple-set resistance training: Recent developments in the controversy

Galvao, D.A., and D.R. Taaffe. Single- vs. multiple-set resistance training: recent developments in the controversy. J. Strength Cond. Res. 18(3):660-667. 2004.-The number of sets in a resistance training program remains a major point of discussion and controversy. Studies prior to 1998 demonstrated inconsistent findings between single-set and multiple-set programs; however, recent evidence suggests that multiple sets promote additional benefits following short- and long-term training. The rationale supporting multiple sets is that the number of sets is part of the exercise volume equation, and the volume of exercise is crucial in producing the stimulus necessary to elicit specific physiological adaptations. The purpose of this paper is to present an overview of recent resistance training studies comparing single and multiple sets. However, it should be noted that studies to date have been conducted in young and middle-aged adults, and it remains to be determined if the additional benefits accrued with multiple-set training also occurs for older adults, especially the frail elderly.

The effectiveness of hylan G-F 20 in patients with knee osteoarthritis: an application of two sets of response criteria developed by the OARSI and one set developed by OMERACT-OARSI

Objective: Secondary analyses of a previously conducted 1-year randomized controlled trial were performed to assess the application of responder criteria in patients with knee osteoarthritis (OA) using different sets of responder criteria developed by the Osteoarthritis Research Society International (OARSI) (Propositions A and B) for intra-articular drugs and Outcome Measures in Arthritis Clinical Trials (OMERACT)-OARSI (Proposition D). Methods: Two hundred fifty-five patients with knee OA were randomized to appropriate care with hylan G-F 20 (AC + H) or appropriate care without hylan G-F 20 (AC). A patient was defined as a responder at month 12 based on change in Western Ontario and McMaster Universities Osteoarthritis Index pain and function (0-100 normalized scale) and patient global assessment of OA in the study knee (at least one-category improvement in very poor, poor, fair, good and very good). All propositions incorporate both minimum relative and absolute changes. Results: Results demonstrated that statistically significant differences in responders between treatment groups, in favor of hylan G-F 20, were detected for Proposition A (AC + H = 53.5%, AC = 25.2%), Proposition B (AC + H = 56.7%, AC = 32.3%) and Proposition D (AC + H = 66.9%, AC = 42.5%). The highest effectiveness in both treatment groups was observed with Proposition D, whereas Proposition A resulted in the lowest effectiveness in both treatment groups. The treatment group differences always exceeded the required 20% minimum clinically important difference between groups established a priori, and were 28.3%, 24.4% and 24.4% for Propositions A, B and D, respectively. Conclusion: This analysis provides evidence for the capacity of OARSI and OMERACT-OARSI responder criteria to detect clinically important statistically detectable differences between treatment groups. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action

We previously reported that bacterial products such as LPS and CpG DNA down-modulated cell surface levels of the Colony Stimulating Factor (CSF)-1 receptor (CSF-1R) on primary murine macrophages in an all-or-nothing manner. Here we show that the ability of bacterial products to down-modulate the CSF-IR rendered bone marrow-derived macrophages (BMM) unresponsive to CSF-1 as assessed by Akt and ERK 1/2 phosphorylation. Using toll-like receptor (th-)9 as a model CSF-1-repressed gene, we show that LPS induced tlr9 expression in BMM only when CSF-1 was present, suggesting that LPS relieves CSF-1-mediated inhibition to induce gene expression. Using cDNA microarrays, we identified a cluster of similarly CSF-1 repressed genes in BMM. By real time PCR we confirmed that the expression of a selection of these genes, including integral membrane protein 2B (itm2b), receptor activity-modifying protein 2 (ramp2) and macrophage-specific gene 1 (mpg-1), were repressed by CSF-1 and were induced by LPS only in the presence of CSF-1. This pattern of gene regulation was also apparent in thioglycollate-elicited peritoneal macrophages (TEPM). LPS also counteracted CSF-1 action to induce mRNA expression of a number of transcription factors including interferon consensus sequence binding protein 1 (Icsbp1), suggesting that this mechanism leads to transcriptional reprogramming in macrophages. Since the majority of in vitro studies on macrophage biology do not include CSF-1, these genes represent a set of previously uncharacterised LPS-inducible genes. This study identifies a new mechanism of macrophage activation, in which LPS (and other toll-like receptor agonists) regulate gene expression by switching off the CSF-1R signal. This finding also provides a biological relevance to the well-documented ability of macrophage activators to down-modulate surface expression of the CSF-1R. (C) 2005 Elsevier GmbH. All rights reserved.

Using continuous measurement to protect a universal set of quantum gates within a perturbed decoherence-free subspace

We consider a universal set of quantum gates encoded within a perturbed decoherence-free subspace of four physical qubits. Using second-order perturbation theory and a measuring device modelled by an infinite set of harmonic oscillators, simply coupled to the system, we show that continuous observation of the coupling agent induces inhibition of the decoherence due to spurious perturbations. We thus advance the idea of protecting or even creating a decoherence-free subspace for processing quantum information.

Incorporating level set methods in Geographical Information Systems (GIS) for land-surface process modelling

Land-surface processes include a broad class of models that operate at a landscape scale. Current modelling approaches tend to be specialised towards one type of process, yet it is the interaction of processes that is increasing seen as important to obtain a more integrated approach to land management. This paper presents a technique and a tool that may be applied generically to landscape processes. The technique tracks moving interfaces across landscapes for processes such as water flow, biochemical diffusion, and plant dispersal. Its theoretical development applies a Lagrangian approach to motion over a Eulerian grid space by tracking quantities across a landscape as an evolving front. An algorithm for this technique, called level set method, is implemented in a geographical information system (GIS). It fits with a field data model in GIS and is implemented as operators in map algebra. The paper describes an implementation of the level set methods in a map algebra programming language, called MapScript, and gives example program scripts for applications in ecology and hydrology.

Edizione critica del volgarizzamento fiorentino dell'Estoire d'Eracles (Biblioteca Medicea Laurenziana, ms. Plut. LXI.45)

Edizione critica del volgarizzamento fiorentino trecentesco dell'"Estoire d'Eracles", contenuto nel ms. Plut. LXI.45 della Biblioteca Medicea Laurenziana, ancora inedito. Si tratta della traduzione in antico francese dell'opera di Guglielmo di Tiro "Historia rerum in partibus transamarinis gestarum", corredata di continuazioni svincolate all'opera latina e in stretto legame con la "Chronique d'Ernoul et de Bernard le Trésorier", che proseguono la narrazione degli eventi in Terrasanta. Il testo fiorentino riporta i fatti d'Oltremare dalla Prima Crociata a circa il 1231. La sua edizione è preceduta da una introduzione letterario-filologica, dalla descrizione del manoscritto e dall'analisi linguistica; seguono un glossario, l'indice dei nomi e dei luoghi.