Ramachandran-type Plots for Glycosidic Linkages: Examples from Molecular Dynamics Simulations using the Glycam06 Force Field

The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates. As in traditional Ramachandran plots, these carbohydrate Ramachandran-type (carb-Rama) plots reveal the coupling between the glycosidic angles by displaying the allowed and disallowed conformational space. Considering two-bond glycosidic linkages, there are 18 possible conformational regions that can be defined by (α, ϕ, ψ) and (β, ϕ, ψ), whereas for three-bond linkages, there are 54 possible regions that can be defined by (α, ϕ, ψ, ω) and (β, ϕ, ψ, ω). Illustrating these ideas are molecular dynamic simulations on an implicitly hydrated oligosaccharide (700 ns) and its eight constituent disaccharides (50 ns/disaccharide). For each linkage, we compare and contrast the oligosaccharide and respective disaccharide carb-Rama plots, validate the simulations and the Glycam06 force field through comparison to experimental data, and discuss the general trends observed in the plots.

Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial

In the RESOLUTE All Comers trial, the Resolute zotarolimus-eluting stent was non-inferior to the Xience V everolimus-eluting stent for the primary stent-related endpoint of target lesion failure (cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation) at 1 year. However, data for long-term safety and efficacy from randomised studies of new generation drug-eluting coronary stents in patients treated in routine clinical practice are scarce. We report the prespecified 2-year clinical outcomes from the RESOLUTE All Comers trial.

Utilization of Probabilistic Models in Short Read Assembly from Second-Generation Sequencing

With the advent of cheaper and faster DNA sequencing technologies, assembly methods have greatly changed. Instead of outputting reads that are thousands of base pairs long, new sequencers parallelize the task by producing read lengths between 35 and 400 base pairs. Reconstructing an organism’s genome from these millions of reads is a computationally expensive task. Our algorithm solves this problem by organizing and indexing the reads using n-grams, which are short, fixed-length DNA sequences of length n. These n-grams are used to efficiently locate putative read joins, thereby eliminating the need to perform an exhaustive search over all possible read pairs. Our goal was develop a novel n-gram method for the assembly of genomes from next-generation sequencers. Specifically, a probabilistic, iterative approach was utilized to determine the most likely reads to join through development of a new metric that models the probability of any two arbitrary reads being joined together. Tests were run using simulated short read data based on randomly created genomes ranging in lengths from 10,000 to 100,000 nucleotides with 16 to 20x coverage. We were able to successfully re-assemble entire genomes up to 100,000 nucleotides in length.

First countrywide survey of third-generation cephalosporin-resistant Escherichia coli from broilers, swine, and cattle in Switzerland

The herd prevalence of third-generation cephalosporin-resistant Escherichia coli (3GC-R-Ec) was determined for broilers (25.0% [95% confidence interval (CI) 17.6-33.7%]), pigs (3.3% [(95% CI 0.4-11.5%]), and cattle (3.9% [95% CI 0.5-13.5%]), using a sampling strategy that was representative of the livestock population slaughtered in Switzerland between October 2010 and April 2011. The 3GC-R-Ec isolates were characterized by the measurement of the MICs of various antibiotics, microarray analyses, analytical isoelectric focusing, polymerase chain reaction and DNA sequencing for bla genes, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. CMY-2 (n = 12), CTX-M-1 (n = 11), SHV-12 (n = 5), TEM-52 (n = 3), CTX-M-15 (n = 2), and CTX-M-3 (n = 1) producers were found. The majority of CMY-2 producers fell into 1 PFGE cluster, which predominantly contained ST61, whereas the CTX-M types were carried by heterogeneous clones of E. coli, as shown by the numerous PFGE profiles and STs that were found. This is the first national Swiss study that focuses on the spread of 3GC-R Enterobacteriaceae among slaughtered animals.

Translation from research to applications

The article summarizes the collective views expressed at the fourth session of the workshop Tissue Engineering-the Next Generation, which was devoted to the translation of results of tissue engineering research into applications. Ernst Hunziker described the paradigm of a dual translational approach, and argued that tissue engineering should be guided by the dimensions and physiological setting of the bodily compartment to be repaired. Myron Spector discussed collagen-glycosaminoglycan (GAG) scaffolds for musculoskeletal tissue engineering. Jeanette Libera focused on the biological and clinical aspects of cartilage tissue engineering, and described a completely autologous procedure for engineering cartilage using the patient's own chondrocytes and blood serum. Arthur Gertzman reviewed the applications of allograft tissues in orthopedic surgery, and outlined the potential of allograft tissues as models for biological and medical studies. Savio Woo discussed a list of functional tissue engineering approaches designed to restore the biochemical and biomechanical properties of injured ligaments and tendons to be closer to that of the normal tissues. Specific examples of using biological scaffolds that have chemoattractants as well as growth factors with unique contact guidance properties to improve their healing process were shown. Anthony Ratcliffe discussed the translation of the results of research into products that are profitable and meet regulatory requirements. Michael Lysaght challenged the proposition that commercial and clinical failures of early tissue engineering products demonstrate a need for more focus on basic research. Arthur Coury described the evolution of tissue engineering products based on the example of Genzyme, and how various definitions of success and failure can affect perceptions and policies relative to the status and advancement of the field of tissue engineering.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Energy harvesting from body motion using rotational micro-generation

Autonomous system applications are typically limited by the power supply operational lifetime when battery replacement is difficult or costly. A trade-off between battery size and battery life is usually calculated to determine the device capability and lifespan. As a result, energy harvesting research has gained importance as society searches for alternative energy sources for power generation. For instance, energy harvesting has been a proven alternative for powering solar-based calculators and self-winding wristwatches. Thus, the use of energy harvesting technology can make it possible to assist or replace batteries for portable, wearable, or surgically-implantable autonomous systems. Applications such as cardiac pacemakers or electrical stimulation applications can benefit from this approach since the number of surgeries for battery replacement can be reduced or eliminated. Research on energy scavenging from body motion has been investigated to evaluate the feasibility of powering wearable or implantable systems. Energy from walking has been previously extracted using generators placed on shoes, backpacks, and knee braces while producing power levels ranging from milliwatts to watts. The research presented in this paper examines the available power from walking and running at several body locations. The ankle, knee, hip, chest, wrist, elbow, upper arm, side of the head, and back of the head were the chosen target localizations. Joints were preferred since they experience the most drastic acceleration changes. For this, a motor-driven treadmill test was performed on 11 healthy individuals at several walking (1-4 mph) and running (2-5 mph) speeds. The treadmill test provided the acceleration magnitudes from the listed body locations. Power can be estimated from the treadmill evaluation since it is proportional to the acceleration and frequency of occurrence. Available power output from walking was determined to be greater than 1mW/cm³ for most body locations while being over 10mW/cm³ at the foot and ankle locations. Available power from running was found to be almost 10 times higher than that from walking. Most energy harvester topologies use linear generator approaches that are well suited to fixed-frequency vibrations with sub-millimeter amplitude oscillations. In contrast, body motion is characterized with a wide frequency spectrum and larger amplitudes. A generator prototype based on self-winding wristwatches is deemed to be appropriate for harvesting body motion since it is not limited to operate at fixed-frequencies or restricted displacements. Electromagnetic generation is typically favored because of its slightly higher power output per unit volume. Then, a nonharmonic oscillating rotational energy scavenger prototype is proposed to harness body motion. The electromagnetic generator follows the approach from small wind turbine designs that overcome the lack of a gearbox by using a larger number of coil and magnets arrangements. The device presented here is composed of a rotor with multiple-pole permanent magnets having an eccentric weight and a stator composed of stacked planar coils. The rotor oscillations induce a voltage on the planar coil due to the eccentric mass unbalance produced by body motion. A meso-scale prototype device was then built and evaluated for energy generation. The meso-scale casing and rotor were constructed on PMMA with the help of a CNC mill machine. Commercially available discrete magnets were encased in a 25mm rotor. Commercial copper-coated polyimide film was employed to manufacture the planar coils using MEMS fabrication processes. Jewel bearings were used to finalize the arrangement. The prototypes were also tested at the listed body locations. A meso-scale generator with a 2-layer coil was capable to extract up to 234 µW of power at the ankle while walking at 3mph with a 2cm³ prototype for a power density of 117 µW/cm³. This dissertation presents the analysis of available power from walking and running at different speeds and the development of an unobtrusive miniature energy harvesting generator for body motion. Power generation indicates the possibility of powering devices by extracting energy from body motion.

Strategies for the Next Generation of Conservation: Lessons from a Life in Environmental Leadership

Successful leadership in the conservation community depends upon leaders with a vision who can engage collaborators in a transaction to create something of enduring value. Ideally, results are achieved in a win-win fashion with other stakeholders. However, a good leader must employ a broader range of tools.