Effect of Control Plot Density, Control Plot Arrangement, and Assumption of Random or Fixed Effects on Nonreplicated Experiments for Germplasm Screening Using Spatial Models

Early generation selection experiments typically involve several hundred to thousands of lines. Various systematic and statistical techniques have been developed to increase effectiveness and efficiencies in such experiments, including the development and application of spatial statistical models. In this study, mixed model equations were used to provide least squares means (LSMEANs) and best linear unbiased predictors (BLUPs) and compare selection effectiveness and efficiencies to observed (Y) and true values in simulated experiments varying in size (10 X 10, 20 X 20 and 30 X 30 grids), control plots densities (0, 5, 10, 20, and 50%), control plot arrangements (high, medium, and low A-optimality), and spatial range of influence (short and long). Results were similar for all grid sizes. In experiments in which the simulated land areas were highly variable (short range), none of the predictors, Y, LSMEAN, or BLUP, were very effective in identifying the true superior genotypes. When the simulated land areas were less variable (long range), use of BLUPs consistently resulted in the highest proportion of true top ranking genotypes identified across all control plot densities, while using the observed values consistently resulted in identification of the lowest proportion of the true top ranking genotypes. Effectiveness of LSMEANs was dependent on control plot density and arrangements.Use of BLUPs for early generation germplasm screening experiments should result in a high effectiveness in selecting truly superior germplasm and high efficiency because of the ability to account for spatial variability with the use of few or no control plots

Post Quantum Cryptography from Mutant Prime Knots

By resorting to basic features of topological knot theory we propose a (classical) cryptographic protocol based on the `difficulty' of decomposing complex knots generated as connected sums of prime knots and their mutants. The scheme combines an asymmetric public key protocol with symmetric private ones and is intrinsecally secure against quantum eavesdropper attacks.Comment: 14 pages, 5 figure

Modelling Li+ Ion Battery Electrode Properties

We formulated two detailed models for an electrolytic cell with particulate electrodes based on a lithium atom concentration dependent Butler-Volmer condition at the interface between electrode particles and the electrolyte. The first was based on a dilute-ion assumption for the electrolyte, while the second assumed that Li ions are present in excess. For the first, we used the method of multiple scales to homogenize this model over the microstructure, formed by the small lithium particles in the electrodes. For the second, we gave rigorous bounds for the effective electrochemical conductivity for a linearized case. We expect similar results and bounds for the "full nonlinear problem" because variational results are generally not adversely affected by a sinh term. Finally we used the asymptotic methods, based on parameters estimated from the literature, to attain a greatly simplified one-dimensional version of the original homogenized model. This simplified model accounts for the fact that diffusion of lithium atoms within individual electrode particles is relatively much faster than that of lithium ions across the whole cell so that lithium ion diffusion is what limits the performance of the battery. However, since most of the potential drop occurs across the Debye layers surrounding each electrode particle, lithium ion diffusion only significantly affects cell performance if there is more or less complete depletion of lithium ions in some region of the electrolyte which causes a break in the current flowing across the cell. This causes catastrophic failure. Providing such failure does not occur the potential drop across the cell is determined by the concentration of lithium atoms in the electrode particles. Within each electrode lithium atom concentration is, to leading order, a function of time only and not of position within the electrode. The depletion of electrode lithium atom concentration is directly proportional to the current being drawn off the cell. This leads one to expect that the potential of the cell gradually drops as current is drawn of it. We would like to emphasize that all the homogenization methods employed in this work give a systematic approach for investigating the effect that changes in the microstructure have on the behaviour of the battery. However, due to lack of time, we have not used this method to investigate particular particle geometries

Non-random retention of protein-coding overlapping genes in Metazoa

<p>Abstract</p> <p>Background</p> <p>Although the overlap of transcriptional units occurs frequently in eukaryotic genomes, its evolutionary and biological significance remains largely unclear. Here we report a comparative analysis of overlaps between genes coding for well-annotated proteins in five metazoan genomes (human, mouse, zebrafish, fruit fly and worm).</p> <p>Results</p> <p>For all analyzed species the observed number of overlapping genes is always lower than expected assuming functional neutrality, suggesting that gene overlap is negatively selected. The comparison to the random distribution also shows that retained overlaps do not exhibit random features: antiparallel overlaps are significantly enriched, while overlaps lying on the same strand and those involving coding sequences are highly underrepresented. We confirm that overlap is mostly species-specific and provide evidence that it frequently originates through the acquisition of terminal, non-coding exons. Finally, we show that overlapping genes tend to be significantly co-expressed in a breast cancer cDNA library obtained by 454 deep sequencing, and that different overlap types display different patterns of reciprocal expression.</p> <p>Conclusion</p> <p>Our data suggest that overlap between protein-coding genes is selected against in Metazoa. However, when retained it may be used as a species-specific mechanism for the reciprocal regulation of neighboring genes. The tendency of overlaps to involve non-coding regions of the genes leads to the speculation that the advantages achieved by an overlapping arrangement may be optimized by evolving regulatory non-coding transcripts.</p

Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non-diabetic exosomes in vitro

Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes-nano-sized, lipid vesicles released from cells-can protect the hearts of non-diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes. Exosomes were isolated by differential centrifugation from non-diabetic and type II diabetic patients, from non-diabetic and Goto Kakizaki type II diabetic rats, and from normoglycaemic and hyperglycaemic endothelial cells. Exosome size and number were not significantly altered by diabetes. CD81 and HSP70 exosome markers were increased in diabetic rat exosomes. However, exosomes from diabetic rats no longer activated the ERK1/2 and HSP27 cardioprotective pathway and were no longer protective in a primary rat cardiomyocytes model of hypoxia and reoxygenation injury. Hyperglycaemic culture conditions were sufficient to impair protection by endothelial exosomes. Importantly, however, exosomes from non-diabetic rats retained the ability to protect cardiomyocytes from diabetic rats. Exosomes from diabetic plasma have lost the ability to protect cardiomyocytes, but protection can be restored with exosomes from non-diabetic plasma. These results support the concept that exosomes may be used to protect cardiomyocytes against ischaemia and reperfusion injury, even in the setting of type II diabetes

Purification of a monoclonal antibody using a novel high-capacity multimodal cation exchange nonwoven membrane

A high-capacity, multimodal cation exchange (MMC) chromatographic membrane was developed by conjugating a multimodal ligand – 2-mercaptopyridine-3-carboxylic acid (MPCA) – on a polybutylene terepthalate (PBT) nonwoven fabric. The membrane features an equilibrium binding capacity of ≈ 1000 mg of human polyclonal IgG (IgG) per g of membrane and dynamic binding capacities (DBC10%) ranging from 77.5 to 115.1 mg/mL (residence times of 1 and 5 min, respectively); these values are 2-to-3-fold higher than those of commercial MMC adsorbents. The effects of buffer composition, pH, conductivity on the binding behavior of the MMC-MPCA membrane were investigated in detail. As a moderate cation exchange binder, MPCA enables effective protein elution using buffers with mild pH (8.0–9.0) and conductivity (≈13 mS/cm), thus circumventing the harsh conditions often needed in multimodal chromatography. The MMC-MPCA membrane was evaluated for product capture in bind-and-elute mode on a Chinese hamster ovary (CHO) cell culture harvest containing therapeutic monoclonal antibodies, using commercial multimodal (Capto MMC and MX-Trp-650M) and affinity (AF-rProtein A HC-650F) resins as controls. The MMC-MPCA membrane outperformed the multimodal resins in terms of binding capacity as well as clearance of host cell proteins (HCPs) and aggregates. The membrane was then evaluated by polishing the mAb from a Protein A eluate in bind-and-elute mode. The MMC-MPCA membrane reduced the level of high molecular weight components from 11% to 4% and the HCP content from 1319.7 ppm to 48.7 ppm (LRV of 1.4). Most notably, proteomics analysis of the product demonstrated the clearance of a significant fraction of persistent, high-risk HCPs from the Protein A eluate