Classical Effective Field Theory for Weak Ultra Relativistic Scattering

Inspired by the problem of Planckian scattering we describe a classical effective field theory for weak ultra relativistic scattering in which field propagation is instantaneous and transverse and the particles' equations of motion localize to the instant of passing. An analogy with the non-relativistic (post-Newtonian) approximation is stressed. The small parameter is identified and power counting rules are established. The theory is applied to reproduce the leading scattering angle for either a scalar interaction field or electro-magnetic or gravitational; to compute some subleading corrections, including the interaction duration; and to allow for non-zero masses. For the gravitational case we present an appropriate decomposition of the gravitational field onto the transverse plane together with its whole non-linear action. On the way we touch upon the relation with the eikonal approximation, some evidence for censorship of quantum gravity, and an algebraic ring structure on 2d Minkowski spacetime.Comment: 29 pages, 2 figures. v4: Duration of interaction is determined in Sec 4 and detailed in App C. Version accepted for publication in JHE

A mutate-and-map protocol for inferring base pairs in structured RNA

Chemical mapping is a widespread technique for structural analysis of nucleic acids in which a molecule's reactivity to different probes is quantified at single-nucleotide resolution and used to constrain structural modeling. This experimental framework has been extensively revisited in the past decade with new strategies for high-throughput read-outs, chemical modification, and rapid data analysis. Recently, we have coupled the technique to high-throughput mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure of not only that nucleotide but also its interaction partner. Carrying out the mutation and mapping for the entire system gives an experimental approximation of the molecules contact map. Here, we give our in-house protocol for this mutate-and-map strategy, based on 96-well capillary electrophoresis, and we provide practical tips on interpreting the data to infer nucleic acid structure.Comment: 22 pages, 5 figure

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients

Magnetic domain tuning and the emergence of bubble domains in the bilayer manganite La 2−2x Sr 1+2x Mn 2 O 7 (x=0.32)

We report a magnetic force microscopy study of the magnetic domain evolution in the layered manganite La2-2x Sr1+2x Mn2O7 (with x = 0.32). This strongly correlated electron compound is known to exhibit a wide range of magnetic phases, including a recently uncovered biskyrmion phase. We observe a continuous transition from dendritic to stripelike domains, followed by the formation of magnetic bubbles due to a field-and temperaturedependent competition between in-plane and out-of-plane spin alignments. The magnetic bubble phase appears at comparable field and temperature ranges as the biskyrmion phase, suggesting a close relation between both phases. Based on our real-space images we construct a temperature-field phase diagram for this composition.open115Ysciescopu

Allylic ionic liquid electrolyte-assisted electrochemical surface passivation of LiCoO2 for advanced, safe lithium-ion batteries

Room-temperature ionic liquid (RTIL) electrolytes have attracted much attention for use in advanced, safe lithium-ion batteries (LIB) owing to their nonvolatility, high conductivity, and great thermal stability. However, LIBs containing RTIL-electrolytes exhibit poor cyclability because electrochemical side reactions cause problematic surface failures of the cathode. Here, we demonstrate that a thin, homogeneous surface film, which is electrochemically generated on LiCoO2 from an RTIL-electrolyte containing an unsaturated substituent on the cation (1-allyl-1-methylpiperidinium bis(trifluoromethanesulfonyl)imide, AMPip-TFSI), can avert undesired side reactions. The derived surface film comprised of a high amount of organic species from the RTIL cations homogenously covered LiCoO2 with a ,25 nm layer and helped suppress unfavorable thermal reactions as well as electrochemical side reactions. The superior performance of the cell containing the AMPip-TFSI electrolyte was further elucidated by surface, electrochemical, and thermal analyses.open1

Enhanced stochastic optimization algorithm for finding effective multi-target therapeutics

<p>Abstract</p> <p>Background</p> <p>For treating a complex disease such as cancer, we need effective means to control the biological network that underlies the disease. However, biological networks are typically robust to external perturbations, making it difficult to beneficially alter the network dynamics by controlling a single target. In fact, multi-target therapeutics is often more effective compared to monotherapies, and combinatory drugs are commonly used these days for treating various diseases. A practical challenge in combination therapy is that the number of possible drug combinations increases exponentially, which makes the prediction of the optimal drug combination a difficult combinatorial optimization problem. Recently, a stochastic optimization algorithm called the Gur Game algorithm was proposed for drug optimization, which was shown to be very efficient in finding potent drug combinations.</p> <p>Results</p> <p>In this paper, we propose a novel stochastic optimization algorithm that can be used for effective optimization of combinatory drugs. The proposed algorithm analyzes how the concentration change of a specific drug affects the overall drug response, thereby making an informed guess on how the concentration should be updated to improve the drug response. We evaluated the performance of the proposed algorithm based on various drug response functions, and compared it with the Gur Game algorithm.</p> <p>Conclusions</p> <p>Numerical experiments clearly show that the proposed algorithm significantly outperforms the original Gur Game algorithm, in terms of reliability and efficiency. This enhanced optimization algorithm can provide an effective framework for identifying potent drug combinations that lead to optimal drug response.</p

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Results of isolated posterolateral corner reconstruction

BACKGROUND: Isolated posterolateral corner (PLC) tears are relatively rare events. Various surgical techniques to treat posterolateral knee instability have been described; because surgical results are linked to cruciate reconstructions it has been difficult to date to define whether one surgical procedure has better prognosis than another. The goal of this study is to determine the clinical outcome of PLC reconstruction following fibular-based technique. MATERIALS AND METHODS: We retrospectively evaluated a case series of patients who received isolated PLC reconstruction between March 2005 and January 2007. Ten patients were surgically treated for isolated injuries and were available for follow-up; average patient age was 27.4 years (range 16-47 years). All patients were treated following the fibular-based technique: double femoral tunnel was performed in six patients, while in the remaining four patients, the reconstruction of the PLC was performed with a single femoral tunnel. Six patients had semitendinosus allograft and four had semitendinosus autograft. All patients had the same evaluation and the same rehabilitation protocol. RESULTS: Mean follow-up was 27.5 months (range 18-40 months). Mean range of motion (ROM) was 143.5 degrees for flexion (range 135-150 degrees) and 0.5 degrees for extension (range 0-3 degrees). Three patients showed 1+ on varus stress test, while on Dial test another three patients showed 10 degrees reduction of external rotation compared with contralateral knee. The average Lysholm score was 94 points (range 83-100), and the mean International Knee Documentation Committee (IKDC) subjective result was 88.48 (range 74-96.5). Based on Lysholm score, the results were excellent in eight knees and good in two knees. On IKDC evaluation, two patients were grade A and eight were grade B. No significant difference in clinical results was observed between single and double femoral tunnel. CONCLUSION: Fibular-based technique showed good results in terms of clinical outcome, restoring varus and rotation stability of knees in treatment of chronic isolated PLC injury

3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes