Deformable plate tectonic models of the southern North Atlantic

Significant, poly-phase deformation occurred prior to, simultaneous with, and after the opening of the North Atlantic Ocean. Understanding this deformation history is essential for understanding the regional development and the mechanisms controlling rifting and subsequent failure or breakup. Here, we primarily use published constraints to construct deformable plate tectonic models for the southern North Atlantic from 200 Ma to present using GPlates. The aim of this work is to test both the capability of the GPlates deformable modelling approach and the reliability of published plate reconstructions. Overall, modelled crustal thickness values at 0 Ma produced from the deformable models show general, regional-scale, similarities with values derived from the inversion of gravity data for crustal thickness. However, the deformable models typically underestimate thinning in marginal basins and overestimate crustal thickness in continental fragments compared to values from gravity inversion. This is possibly due to: 1) thinning occurring earlier than the 200 Ma start time modelled, 2) variations in the original crustal thickness, 3) depth-dependent stretching, 4) rigid blocks undergoing some degree of thinning, and 5) variations in the mesh density of the models. The results demonstrate that inclusion of micro-continental fragments, and locally defined limits of continental crust, generally produce results more akin to observations. One exception is the Grand Banks where global GPlates models produce more realistic deformation, likely due to the inclusion of the exhumed domains continent-ward of the transition zone boundary. Results also indicate that Flemish Cap rotation is required to provide a reasonable fit between North America and Iberia, with the palaeo-position of the Flemish Cap likely to be the proto-Orphan sub-basins. Moreover, the East and West Orphan sub-basins formed separately due to the respective rotations of the Flemish Cap and the Orphan Knoll, which was likely associated with other continental fragments that subsequently contributed to the thicker crust forming the boundary between the East and West Orphan basins. The results also suggest a link between tectonic and magmatic processes. For example, the inclusion of an Orphan Knoll micro-continental block results in greater extension (higher beta factors) in the northern West Orphan Basin near the termination of the Charlie-Gibbs Fracture Zone, and the site of the Charlie-Gibbs Volcanic Province (CGVP). Thus, we infer that the CGVP was likely influenced by plate tectonic processes through the concentration of strain resulting from interaction in proximity to the transform system. Finally, marginal basins that were considered to be conjugate and thus related, may only appear conjugate through later rotation of micro-continental blocks, and thus their genesis is not directly related

Explicit approximate controllability of the Schr\"odinger equation with a polarizability term

We consider a controlled Schr\"odinger equation with a dipolar and a polarizability term, used when the dipolar approximation is not valid. The control is the amplitude of the external electric field, it acts non linearly on the state. We extend in this infinite dimensional framework previous techniques used by Coron, Grigoriu, Lefter and Turinici for stabilization in finite dimension. We consider a highly oscillating control and prove the semi-global weak $H^2$ stabilization of the averaged system using a Lyapunov function introduced by Nersesyan. Then it is proved that the solutions of the Schr\"odinger equation and of the averaged equation stay close on every finite time horizon provided that the control is oscillating enough. Combining these two results, we get approximate controllability to the ground state for the polarizability system

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Modeling Airline Frequency Competition for Airport Congestion Mitigation

Demand often exceeds capacity at congested airports. Airline frequency competition is partially responsible for the growing demand for airport resources. We propose a game-theoretic model for airline frequency competition under slot constraints. The model is solved to obtain a Nash equilibrium using a successive optimizations approach, wherein individual optimizations are performed using a dynamic programming-based technique. The model predictions are validated against actual frequency data, with the results indicating a close fit to reality. We use the model to evaluate different strategic slot allocation schemes from the perspectives of the airlines and the passengers. The most significant result of this research shows that a small reduction in the total number of allocated slots translates into a substantial reduction in flight and passenger delays and also a considerable improvement in airlines' profits

Retinoic acid-responsive CD8 effector T-cells are selectively increased in IL-23-rich tissue in gastrointestinal GvHD.

Gastrointestinal (GI) graft-versus-host disease (GvHD) is a major barrier in allogeneic hematopoietic stem-cell transplantation (AHST). The metabolite retinoic acid (RA) potentiates GI-GvHD in mice via alloreactive T-cells expressing the RA-receptor-alpha (RARα), but the role of RA-responsive cells in human GI-GvHD remains undefined. We therefore used conventional and novel sequential immunostaining and flow cytometry to scrutinize RA-responsive T-cells in tissues and blood of AHST patients and characterize the impact of RA on human T-cell alloresponses. Expression of RARα by human mononuclear cells was increased after RA exposure. RARαhi mononuclear cells were increased in GI-GvHD tissue, contained more cellular RA-binding proteins, localized with tissue damage and correlated with GvHD severity and mortality. Using a targeted candidate protein approach we predicted the phenotype of RA-responsive T-cells in the context of increased microenvironmental IL-23. Sequential immunostaining confirmed the presence of a population of RARahi CD8 T-cells with the predicted phenotype, co-expressing the effector T-cell transcription factor T-bet and the IL-23-specific receptor. These cells were increased in GI- but not skin-GvHD tissues and were also selectively expanded in GI-GvHD patient blood. Finally, functional approaches demonstrated RA predominantly increased alloreactive GI-tropic RARahi CD8 effector T-cells, including cells with the phenotype identified in vivo. IL-23-rich conditions potentiated this effect by selectively increasing b7 integrin expression on CD8 effector T-cells and reducing CD4 T-cells with a regulatory cell phenotype. In conclusion we have identified a population of RA-responsive effector T-cells with a distinctive phenotype which are selectively expanded in human GI-GvHD and represent a potential new therapeutic target

Eye tracking as an MT evaluation technique

Eye tracking has been used successfully as a technique for measuring cognitive load in reading, psycholinguistics, writing, language acquisition etc. for some time now. Its application as a technique for measuring the reading ease of MT output has not yet, to our knowledge, been tested. We report here on a preliminary study testing the use and validity of an eye tracking methodology as a means of semi-automatically evaluating machine translation output. 50 French machine translated sentences, 25 rated as excellent and 25 rated as poor in an earlier human evaluation, were selected. Ten native speakers of French were instructed to read the MT sentences for comprehensibility. Their eye gaze data were recorded non-invasively using a Tobii 1750 eye tracker. The average gaze time and fixation count were found to be higher for the “bad” sentences, while average fixation duration and pupil dilations were not found to be substantially different for output rated as good and output rated as bad. Comparisons between HTER scores and eye gaze data were also found to correlate well with gaze time and fixation count, but not with pupil dilation and fixation duration. We conclude that the eye tracking data, in particular gaze time and fixation count, correlate reasonably well with human evaluation of MT output but fixation duration and pupil dilation may be less reliable indicators of reading difficulty for MT output. We also conclude that eye tracking has promise as a semi-automatic MT evaluation technique, which does not require bi-lingual knowledge, and which can potentially tap into the end users’ experience of machine translation output

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation