Dynamic Data Visualization with Weave and Brain Choropleths

This article introduces the neuroimaging community to the dynamic visualization workbench, Weave (https://www.oicweave.org/), and a set of enhancements to allow the visualization of brain maps. The enhancements comprise a set of brain choropleths and the ability to display these as stacked slices, accessible with a slider. For the first time, this allows the neuroimaging community to take advantage of the advanced tools already available for exploring geographic data. Our brain choropleths are modeled after widely used geographic maps but this mashup of brain choropleths with extant visualization software fills an important neuroinformatic niche. To date, most neuroinformatic tools have provided online databases and atlases of the brain, but not good ways to display the related data (e.g., behavioral, genetic, medical, etc). The extension of the choropleth to brain maps allows us to leverage general-purpose visualization tools for concurrent exploration of brain images and related data. Related data can be represented as a variety of tables, charts and graphs that are dynamically linked to each other and to the brain choropleths. We demonstrate that the simplified region-based analyses that underlay choropleths can provide insights into neuroimaging data comparable to those achieved by using more conventional methods. In addition, the interactive interface facilitates additional insights by allowing the user to filter, compare, and drill down into the visual representations of the data. This enhanced data visualization capability is useful during the initial phases of data analysis and the resulting visualizations provide a compelling way to publish data as an online supplement to journal articles.     

Extended Preclinical Safety,Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate

We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from <10% to >30%) and mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.     

A Monte–Carlo step-by-step simulation code of the non-homogeneous chemistry of the radiolysis of water and aqueous solutions. Part I: theoretical framework and implementation

The importance of the radiolysis of water in irradiation of biological systems has motivated considerable theoretical and experimental work in the radiation chemistry of water and aqueous solutions. In particular, Monte–Carlo simulations of radiation track structure and non-homogeneous chemistry have greatly contributed to the understanding of experimental results in radiation chemistry of heavy ions. Actually, most simulations of the non-homogeneous chemistry are done using the Independent Reaction Time (IRT) method, a very fast technique. The main limitation of the IRT method is that the positions of the radiolytic species are not calculated as a function of time, which is needed to simulate the irradiation of more complex systems. Step-by-step (SBS) methods, which are able to provide such information, have been used only sparsely because these are time consuming in terms of calculation. Recent improvements in computer performance now allow the regular use of the SBS method in radiation chemistry. In the present paper, the first of a series of two, the SBS method is reviewed in detail. To these ends, simulation of diffusion of particles and chemical reactions in aqueous solutions is reviewed, and implementation of the program is discussed. Simulation of model systems is then performed to validate the adequacy of stepwise diffusion and reaction schemes. In the second paper, radiochemical yields of simulated radiation tracks calculated by the SBS program in different conditions of LET, pH, and temperature are compared with results from the IRT program and experimental data.     

Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism

Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.     

Comparative analysis of different TaqMan real-time RT-PCR assays for the detection of swine Hepatitis E virus and integration of Feline calicivirus as internal control

Aims:  The aim of this study was to compare the performance of four TaqMan RT-PCR assays with a commonly used nested RT-PCR and to include the Feline calicivirus (FCV) as an internal control.
Methods and Results:  RNA extracted from 87 swine faecal samples and 103 swine blood samples was subjected to different detection systems. Faecal samples naturally contaminated with Hepatitis E virus (HEV) and negative samples were artificially inoculated with 3·2 × 10³ PFU of FCV. Detection results obtained on faecal and plasma samples were 35·6% and 4·9% with the nested RT-PCR assay, 8·0% and 0%, 0% and 0%, 13·8% and 0% and 36·8% and 3·9% with TaqMan systems A, B, C and D respectively. The Ct means obtained with the multiplex TaqMan assay were 30·11 and 30·43 for the detection of FCV with HEV contaminated samples and negative samples.
Conclusions:  The TaqMan system D was more suitable for the detection of swine HEV strains than the three others and FCV was integrated successfully as an internal control.
Significance and Impact of the Study:  FCV was demonstrated as an efficient control to monitor the RNA extraction process and HEV amplification procedure in a multiplex HEV/FCV TaqMan assay. This control would be helpful in limiting false negative results.     

Synthesis and degradation of endothelin-1

The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout of both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each sub-isoform for ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (1-31) and ET-1 (1-32), respectively. Other enzymes, such as the neutral endopeptidase 24-11, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (1-31). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor peptide reported to date.     

Removal of indicator bacteria, human enteric viruses, Giardia cysts, and Cryptosporidium oocysts at a large wastewater primary treatment facility

Pathogens and fecal indicator bacteria occurrence and removal were studied for a period of 6 months at the Montreal Urban Community wastewater treatment facility. With a capacity of about 7.6 million cubic metres per day (two billion U.S. gallons per day), it is the largest primary physico-chemical treatment plant in America. The plant discharges a nondisinfected effluent containing about 20 mg/L of suspended matter and 0.5 mg/L of total phosphorus on the basis of average annual concentrations. BDO5 (annual mean) is 75 mg/L before treatment and 32 mg/L after treatment. Samples were collected for a period of 6 months, and they demonstrated that the plant was not efficient at removing indicator bacteria and the pathogens tested. Fecal coliforms were the most numerous of the indicator bacteria and their removal averaged 25%. Fecal streptococci removal was 29%, while Escherichia coli removal was 12%. In untreated sewage, fecal coliforms, E. coli, and human enteric viruses were more numerous in summer and early autumn. Fecal streptococci counts remained relatively similar throughout the period. Clostridium perfringens removal averaged 51%. Giardia cysts levels were not markedly different throughout the study period, and 76% of the cysts were removed by treatment. Cryptosporidium oocyst counts were erratic, probably due to the methods, and removal was 27%. Human enteric viruses were detected in all samples of raw and treated wastewater with no removal observed (0%). Overall, the plant did not perform well for the removal of fecal indicator bacteria, human enteric viruses, or parasite cysts. Supplementary treatment and disinfection were recommended to protect public health. Various alternatives are being evaluated.     

Experimental validation of a statistical model for evaluating the past or future magnetic field exposures of a population living near power lines

This study was designed to provide an experimental validation for a statistical model predicting past or future exposures to magnetic fields (MF) from power lines. The model estimates exposure, combining the distribution of ambient MF in the absence of power lines with the distribution of past or future MF produced by power lines. In the study, validation is carried out by comparing exposures predicted by the model with the actual measurements obtained from a large-scale epidemiological study. The comparison was made for a group of 220 women living near a 735 kV power line. Knowing that the individual arithmetic means of MF exposures follow a log-normal distribution, the Pearson correlation between the log-transformed measured means and the calculated ones was determined and found to be 0.77. Predicted values of MF exposures were slightly lower than measured values. The calculated geometric mean of the group was 0.33 microT, compared to 0.38 microT for the measured geometric mean. The present study shows good agreement between the measured MF exposure of an individual inside a house near a 735 kV line and the MF exposure calculated using a statistical model.