Development of a transient large strain contact method for biological heart valve simulations

A new 2D method to implement transient contact using Comsol Multiphysics (finite element analysis software that enables multiphysics simulations) is described, which is based on Hertzian contact. This method is compared to the existing (default) contact method that does not enable real transient simulations, but instead performs steady-state solutions where time is a constant. The two types of contact modelling have been applied to simple 2D biological heart valve models, undergoing strains in the region of 10% under 20 kPa pressure (applied over 0.3 s). Both the methods predicted comparable stress patterns, locations of peak stresses, deformations and directions of principal stress. The default contact method predicted slightly greater contact stresses, but spreads over a shorter surface length than the new contact method. The default contact method is useful for contact systems with little transient dependency, due to ease of use. However, where transient conditions are important the new contact method is preferred.     

Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

Background  

Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies.     

Identification of genes required for de novo DNA methylation in Arabidopsis

De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 is targeted to DNA by small interfering RNAs (siRNAs) in a process known as RNA-directed DNA Methylation (RdDM). While several components of the RdDM pathway are known, a functional understanding of the underlying mechanism is far from complete. We employed both forward and reverse genetic approaches to identify factors involved in de novo methylation. We utilized the FWA transgene, which is methylated and silenced when transformed into wild-type plants, but unmethylated and expressed when transformed into de novo methylation mutants. Expression of FWA is marked by a late-flowering phenotype, which is easily scored in mutant versus wild-type plants. By reverse genetics we discovered the requirement for known RdDM effectors AGO6 and NRPE5a for efficient de novo methylation. A forward genetic approach uncovered alleles of several components of the RdDM pathway, including alleles of clsy1, ktf1 and nrpd/e2, which have not been previously shown to be required for the initial establishment of DNA methylation. Mutations were mapped and genes cloned by both traditional and whole genome sequencing approaches. The methodologies and the mutant alleles discovered will be instrumental in further studies of de novo DNA methylation.Key words: DNA methylation, Arabidopsis, de novo, genetic screen, whole-genome sequencing     

Sugarcane Internode Composition During Crop Development

Sugarcane sugar and bagasse can be utilized for the production of ethanol or other biofuels. A better understanding of the changes in composition with development along the stalk and with crop development will maximize the usage of sugarcane for this purpose. Two experiments were designed to elucidate internode composition changes during the growing season. In experiment 1, an internode of stalks of 5 modern cultivars were marked at the start of elongation, and then sampled every 1 to 2?weeks from July until October. Sugars were extracted and assayed, and a sequential detergent method was used to estimate hemicellulose, cellulose, and lignin contents. In experiment 2, internodes 1, 3, 5, 7, 9, and 11 down the stalk were sampled in late July (grand growth) and late September (ripening). Internode length, fresh weight, dry weight, water content, and sugar contents were determined as well as cell wall composition. Both experiments were repeated in 2?years. As internodes elongated, total sugar increased, and hemicellulose decreased as a proportion of neutral detergent fiber, while cellulose and lignin increased. After elongation, sucrose and lignin increased, and cellulose content decreased with internode age. The variability in cell wall composition among the five cultivars suggests that selection for desirable composition may be possible. In Experiment 2, hemicellulose contents were lower, and lignin and ash contents were higher at ripening than during grand growth. Delaying sugarcane harvest to maximize sucrose content may decrease bagasse suitability for cellulosic ethanol production because of the increased lignin content.     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.     

Prey behavior, age-dependent vulnerability, and predation rates

Variation in the temporal pattern of vulnerability can provide important insights into predator-prey relationships and the evolution of antipredator behavior. We illustrate these points with a system that has coyotes (Canis latrans) as a predator and two species of congeneric deer (Odocoileus spp.) as prey. The deer employ different antipredator tactics (aggressive defense vs. flight) that result in contrasting patterns of age-dependent vulnerability in their probability of being captured when encountered by coyotes. We use long-term survival data and a simple mathematical model to show that (1) species differences in age-dependent vulnerability are reflected in seasonal predation rates and (2) seasonal variation in prey vulnerability and predator hunt activity, which can be associated with the availability of alternative prey, interact to shape seasonal and annual predation rates for each prey species. Shifting hunt activity from summer to winter, or vice versa, alleviated annual mortality on one species and focused it on the other. Our results indicate that seasonal variation in prey vulnerability and hunt activity interact to influence the impact that a predator has on any particular type of prey. Furthermore, these results indicate that seasonal variation in predation pressure is an important selection pressure shaping prey defenses.     

NlpC/P60 domain‐containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan

A subset of proteins containing NlpC/P60 domains are bacterial peptidoglycan hydrolases that cleave noncanonical peptide linkages and contribute to cell wall remodeling as well as cell separation during late stages of division. Some of these proteins have been shown to cleave peptidoglycan in Mycobacterium tuberculosis and play a role in Mycobacterium marinum virulence of zebra fish; however, there are still significant knowledge gaps concerning the molecular function of these proteins in Mycobacterium avium subspecies paratuberculosis (MAP). The MAP genome sequence encodes five NlpC/P60 domain‐containing proteins. We describe atomic resolution crystal structures of two such MAP proteins, MAP_1272c and MAP_1204. These crystal structures, combined with functional assays to measure peptidoglycan cleavage activity, led to the observation that MAP_1272c does not have a functional catalytic core for peptidoglycan hydrolysis. Furthermore, the structure and sequence of MAP_1272c demonstrate that the catalytic residues normally required for hydrolysis are absent, and the protein does not bind peptidoglycan as efficiently as MAP_1204. While the NlpC/P60 catalytic triad is present in MAP_1204, changing the catalytic cysteine‐155 residue to a serine significantly diminished catalytic activity, but did not affect binding to peptidoglycan. Collectively, these findings suggest a broader functional repertoire for NlpC/P60 domain‐containing proteins than simply hydrolases.