AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

SUMMARY: We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. AVAILABILITY: The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

Regenerating cortical connections in a dish: the entorhino-hippocampal organotypic slice co-culture as tool for pharmacological screening of molecules promoting axon regeneration

We present a method for using long-term organotypic slice co-cultures of the entorhino-hippocampal formation to analyze the axon-regenerative properties of a determined compound. The culture method is based on the membrane interphase method, which is easy to perform and is generally reproducible. The degree of axonal regeneration after treatment in lesioned cultures can be seen directly using green fluorescent protein (GFP) transgenic mice or by axon tracing and histological methods. Possible changes in cell morphology after pharmacological treatment can be determined easily by focal in vitro electroporation. The well-preserved cytoarchitectonics in the co-culture facilitate the analysis of identified cells or regenerating axons. The protocol takes up to a month.

The use of 3D planning in facial surgery: Preliminary observations.

Three-dimensional (3D) planning is becoming a more commonly used tool in maxillofacial surgery. At first used only virtually, 3D planning now also enables the creation of useful intraoperative aids such as cutting guides, which decrease the operative difficulty. In our center, we have used 3D planning in various domains of facial surgery and have investigated the advantages of this technique. We have also addressed the difficulties associated with its use. 3D planning increases the accuracy of reconstructive surgery, decreases operating time, whilst maintaining excellent esthetic results. However, its use is restricted to osseous reconstruction at this stage and once planning has been undertaken, it cannot be reversed or altered intraoperatively. Despite the attractive nature of this new tool, its uses and practicalities must be further evaluated. In particular, cost-effectiveness, hospital stay, and patient perceived benefits must be assessed.

Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells.

Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ("thymus crosstalk") are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.

Evaluation of a clinical tool for early etiology identification in status epilepticus.

OBJECTIVES: Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. METHODS: This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. RESULTS: Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4-89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4-96) (κ = 0.81). SIGNIFICANCE: This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment.

Cutting edge: a novel viral TNF receptor superfamily member in virulent strains of human cytomegalovirus.

The UL144 open reading frame found in clinical isolates of human CMV (HCMV) encodes a structural homologue of the herpesvirus entry mediator, a member of the TNFR superfamily. UL144 is a type I transmembrane glycoprotein that is expressed early after infection of fibroblasts; however, it is retained intracellularly. A YXXZ motif in the highly conserved cytoplasmic tail contributes to UL144 subcellular distribution. The finding that no known ligand of the TNF family binds UL144 suggests that its mechanism of action is distinct from other known viral immune evasion genes. Specific Abs to UL144 can be detected in the serum of a subset of HCMV seropositive individuals infected with HIV. This work establishes a novel molecular link between the TNF superfamily and herpesvirus that may contribute to the ability of HCMV to escape immune clearance.

A Transportation Safety Planning Tool for the City of Ames, August 2011

The historically-reactive approach to identifying safety problems and mitigating them involves selecting black spots or hot spots by ranking locations based on crash frequency and severity. The approach focuses mainly on the corridor level without taking the exposure rate (vehicle miles traveled) and socio-demographics information of the study area, which are very important in the transportation planning process, into consideration. A larger study analysis unit at the Transportation Analysis Zone (TAZ) level or the network planning level should be used to address the needs of development of the community in the future and incorporate safety into the long-range transportation planning process. In this study, existing planning tools (such as the PLANSAFE models presented in NCHRP Report 546) were evaluated for forecasting safety in small and medium-sized communities, particularly as related to changes in socio-demographics characteristics, traffic demand, road network, and countermeasures. The research also evaluated the applicability of the Empirical Bayes (EB) method to network-level analysis. In addition, application of the United States Road Assessment Program (usRAP) protocols at the local urban road network level was investigated. This research evaluated the applicability of these three methods for the City of Ames, Iowa. The outcome of this research is a systematic process and framework for considering road safety issues explicitly in the small and medium-sized community transportation planning process and for quantifying the safety impacts of new developments and policy programs. More specifically, quantitative safety may be incorporated into the planning process, through effective visualization and increased awareness of safety issues (usRAP), the identification of high-risk locations with potential for improvement, (usRAP maps and EB), countermeasures for high-risk locations (EB before and after study and PLANSAFE), and socio-economic and demographic induced changes at the planning-level (PLANSAFE).

Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology.

The ability to express tightly controlled amounts of endogenous and recombinant proteins in plant cells is an essential tool for research and biotechnology. Here, the inducibility of the soybean heat-shock Gmhsp17.3B promoter was addressed in the moss Physcomitrella patens, using beta-glucuronidase (GUS) and an F-actin marker (GFP-talin) as reporter proteins. In stably transformed moss lines, Gmhsp17.3B-driven GUS expression was extremely low at 25 degrees C. In contrast, a short non-damaging heat-treatment at 38 degrees C rapidly induced reporter expression over three orders of magnitude, enabling GUS accumulation and the labelling of F-actin cytoskeleton in all cell types and tissues. Induction levels were tightly proportional to the temperature and duration of the heat treatment, allowing fine-tuning of protein expression. Repeated heating/cooling cycles led to the massive GUS accumulation, up to 2.3% of the total soluble proteins. The anti-inflammatory drug acetyl salicylic acid (ASA) and the membrane-fluidiser benzyl alcohol (BA) also induced GUS expression at 25 degrees C, allowing the production of recombinant proteins without heat-treatment. The Gmhsp17.3B promoter thus provides a reliable versatile conditional promoter for the controlled expression of recombinant proteins in the moss P. patens.

MADAP, a flexible clustering tool for the interpretation of one-dimensional genome annotation data.

A recurring task in the analysis of mass genome annotation data from high-throughput technologies is the identification of peaks or clusters in a noisy signal profile. Examples of such applications are the definition of promoters on the basis of transcription start site profiles, the mapping of transcription factor binding sites based on ChIP-chip data and the identification of quantitative trait loci (QTL) from whole genome SNP profiles. Input to such an analysis is a set of genome coordinates associated with counts or intensities. The output consists of a discrete number of peaks with respective volumes, extensions and center positions. We have developed for this purpose a flexible one-dimensional clustering tool, called MADAP, which we make available as a web server and as standalone program. A set of parameters enables the user to customize the procedure to a specific problem. The web server, which returns results in textual and graphical form, is useful for small to medium-scale applications, as well as for evaluation and parameter tuning in view of large-scale applications, requiring a local installation. The program written in C++ can be freely downloaded from ftp://ftp.epd.unil.ch/pub/software/unix/madap. The MADAP web server can be accessed at http://www.isrec.isb-sib.ch/madap/.

2 Iowa Safety Efforts: Analyst Tool & Location Aggregation Project, July 8, 2003

Report produced by the Iowa Department of Transportation about Iowa Safety with Tools and Aggregation.