The emergence of insect resistance in Bt-corn: implication of resistance management information under uncertainty

"The successful management of transgenic technology is likely to depend on the economic behavioral response of farmers to the regulated use of transgenic crops. A well-studied example is the widespread use of Bt-corn, in the United States, and elsewhere, to control the European Corn Borer, a major corn pest. The extensive use of Bt-corn has led to concerns about the emergence of insect resistance. The United States Environment Protection Agency addressed this potential problem by developing an insect resistance management strategy, based, in part, on complex mathematical models using detailed biological assumptions about the population genetics and life history of the European Corn Borer. However, seed companies and others have sometimes used simpler deterministic profit models to justify the economics of Bt-corn to potential growers. Therefore an over reliance, by regulatory agencies, on complex modeling approaches may obscure the likely economic behavioral response of farmers who rely on these less complex models. However, the determinants of adoption are numerous, profit being one of them. We develop a simple model for the spread of resistance based on the logistic growth equation and use it to investigate the effect of uncertainty on farmer decisions to plant Bt-corn and follow EPA management rules. The model results suggest that planting Bt-corn is an optimal strategy under the type of uncertainty assumed in the model and that short-term economic behavior is likely to lead to the Environment Protection Agency management rules not being followed. Our results add weight to existing work on this problem." Authors' AbstractBt-corn, logistic growth, Monte Carlo methods, Corn, Environmental protection, Economics Methodology,

Evolving Recursive Programs using Non-recursive Scaffolding

Genetic programming has proven capable of evolving solutions to a wide variety of problems. However, the successes have largely been with programs without iteration or recursion; evolving recursive programs has turned out to be particularly challenging. The main obstacle to evolving recursive programs seems to be that they are particularly fragile to the application of search operators: a small change in a correct recursive program generally produces a completely wrong program. In this paper, we present a simple and general method that allows us to pass back and forth from a recursive program to an associated non-recursive program. Finding a recursive program can be reduced to evolving non-recursive programs followed by converting the optimum non-recursive program found to the associated optimum recursive program. This avoids the fragility problem above, as evolution does not search the space of recursive programs. We present promising experimental results on a test-bed of recursive problems

Polymer-drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive, neurodegenerative condition. There are clear markers for the presence and progression of the disease, including β-amyloid (Aβ) plaques and Tau tangles, with many potential causes debated in the scientific community. Most existing treatments only provide symptomatic solutions. Due to poor aqueous solubility and possibly limited uptake across the blood–brain barrier (BBB), medications targeting the hallmarks of AD are still under study despite enormous efforts. Recently, nanoparticle-based drug delivery systems have demonstrated remarkable promise as precision medicines that may effectively increase bioavailability, permeate the BBB, and improve the targeting ability of a variety of pharmaceuticals. Polymer therapeutics have made tremendous progress in recent years, particularly in cancer treatment. Polymer–drug conjugates (PDCs) typically have a longer half-life, higher stability, and enhanced water solubility. Polymers serve as carriers for the administration of drugs, proteins, targeting moieties, and imaging agents in polymeric and macromolecular prodrugs. Numerous commercially viable PDCs for the treatment of various diseases have already proved their potential. This paper focuses mainly on the rationale for the design, synthesis, and potential use of PDCs as a multi-target treatment for neurodegenerative diseases

Cambrian edrioasteroid reveals new mechanism for secondary reduction of the skeleton in echinoderms

Echinoderms are characterized by a distinctive high-magnesium calcite endoskeleton as adults, but elements of this have been drastically reduced in some groups. Herein, we describe a new pentaradial echinoderm, Yorkicystis haefneri n. gen. n. sp., which provides, to our knowledge, the oldest evidence of secondary non-mineralization of the echinoderm skeleton. This material was collected from the Cambrian Kinzers Formation in York (Pennsylvania, USA) and is dated as ca 510 Ma. Detailed morphological observations demonstrate that the ambulacra (i.e. axial region) are composed of flooring and cover plates, but the rest of the body (i.e. extraxial region) is preserved as a dark film and lacks any evidence of skeletal plating. Moreover, X-ray fluorescence analysis reveals that the axial region is elevated in iron. Based on our morphological and chemical data and on taphonomic comparisons with other fossils from the Kinzers Formation, we infer that the axial region was originally calcified, while the extraxial region was non-mineralized. Phylogenetic analyses recover Yorkicystis as an edrioasteroid, indicating that this partial absence of skeleton resulted from a secondary reduction. We hypothesize that skeletal reduction resulted from lack of expression of the skeletogenic gene regulatory network in the extraxial body wall during development. Secondary reduction of the skeleton in Yorkicystis might have allowed for greater flexibility of the body wall

Effect of Airborne-particle Abrasion on 3-dimensional Surface Roughness and Characteristic Failure Load of Fiber-reinforced Posts

Statement of problem Debonding is the most common complication of fiber-reinforced posts (FRPs). Airborne-particle abrasion (APA) has been suggested to increase resin cement adhesion to the surface of FRPs. However, which abrasion protocol is the most favorable is unclear. Purpose The purpose of this in vitro study was to compare the surface roughness and characteristic failure load of three FRP systems following different APA protocols. Material and methods A total of 150 posts from 3 manufacturers (glass FRP, quartz FRP, and zirconia-enriched glass FRP) were randomly assigned to different surface treatments (NT: no treatment—control; E0: cleaned with 96% ethanol solution; E2: APA for 2 seconds/mm2—ethanol cleaned, E5: APA for 5 seconds/mm2—ethanol cleaned; and E10: APA for 10 seconds/mm2—ethanol cleaned) forming 15 groups in total. APA was performed with 50-μm aluminum oxide. Each post was observed under a 3-dimensional (3D) laser microscope, and average 3D surface roughness (Sa) was measured. Failure was induced with a universal testing machine. Two specimens per group were evaluated under the same microscope to evaluate failure patterns. Surface roughness data were analyzed with the Welch ANOVA (α=.05), followed by the post hoc Games-Howell test. Failure load differences were determined by 2-parameter Weibull statistics and likelihood ratio contour plots (95% confidence bounds). Results Statistically significant differences were found in the mean surface roughness among the groups (Welch ANOVA, P Conclusions APA significantly increased surface roughness in all post systems. APA effects on characteristic failure load were dependent on the material used

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials

The Mu subunit of Plasmodium falciparum clathrin-associated adaptor protein 2 modulates in vitro parasite response to artemisinin and quinine.

The emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance, ap2-mu (encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasite Plasmodium chabaudi (pcap2-mu). Furthermore, analysis in Kenyan malaria patients of polymorphisms in the Plasmodium falciparum ap2-mu homologue, pfap2-mu, found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survival in vivo following combination treatments which included artemisinin derivatives. Here, we characterize the role of pfap2-mu in mediating the in vitro antimalarial drug response of P. falciparum by generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form of pfap2-mu. Transgenic parasites carrying the pfap2-mu 160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-h in vitro test, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence that pfap2-mu variants can modulate parasite sensitivity to quinine. No evidence was found that pfap2-mu variants contribute to the slow-clearance phenotype exhibited by P. falciparum in Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence that pfap2-mu can modulate P. falciparum responses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance