On the Unitarity of D=9,10,11 Conformal Supersymmetry

We consider the unitarity of D=9,10,11 conformal supersymmetry using the recently established classification of the UIRs of the superalgebras osp(1|2n,R).Comment: 7 pages, LATEX2e{czjphys} (amsmath,amssymb); v3: important corrections, Plenary talk by VKD at the XIII Colloquium "Quantum Groups and Integrable Systems", Prague, 17-19.6.2004; to appear in Czech. J. Phys.; v4: small corrections to coincide with journal versio

AMMOS: A Software Platform to Assist in silico Screening

Three software packages based on the common platform of AMMOS (Automated Molecular Mechanics Optimization tool for in silico Screening) for assisting virtual ligand screening purposes have been recently developed. DG-AMMOS allows generation of 3D conformations of small molecules using distance geometry and molecular mechanics optimization. AMMOS_SmallMol is a package for structural refinement of compound collections that can be used prior to docking experiments. AMMOS_ProtLig is a package for energy minimization of protein-ligand complexes. It performs an automatic procedure for molecular mechanics minimization at different levels of flexibility - from rigid to fully flexible structures of both the ligand and the receptor. The packages have been tested on small molecules with a high structural diversity and proteins binding sites of completely different geometries and physicochemical properties. The platform is developed as an open source software and can be used in a broad range of in silico drug design studies

Comparison of 30 THz impulsive burst time development to microwaves, H-alpha, EUV, and GOES soft X-rays

The recent discovery of impulsive solar burst emission in the 30 THz band is raising new interpretation challenges. One event associated with a GOES M2 class flare has been observed simultaneously in microwaves, H-alpha, EUV, and soft X-ray bands. Although these new observations confirm some features found in the two prior known events, they exhibit time profile structure discrepancies between 30 THz, microwaves, and hard X-rays (as inferred from the Neupert effect). These results suggest a more complex relationship between 30 THz emission and radiation produced at other wavelength ranges. The multiple frequency emissions in the impulsive phase are likely to be produced at a common flaring site lower in the chromosphere. The 30 THz burst emission may be either part of a nonthermal radiation mechanism or due to the rapid thermal response to a beam of high-energy particles bombarding the dense solar atmosphere.Comment: accepted to Astronomy and Astrophysic

Ultrafast temporal evolution of interatomic Coulombic decay in NeKr dimers

We investigate interatomic Coulombic decay in NeKr dimers after neon inner-valence photoionization [Ne+(2s-1)] using a synchrotron light source. We measure with high energy resolution the two singly charged ions of the Coulomb-exploding dimer dication and the photoelectron in coincidence. By carefully tracing the post-collision interaction between the photoelectron and the emitted ICD electron we are able to probe the temporal evolution of the state as it decays. Although the ionizing light pulses are 80 picoseconds long, we determine the lifetime of the intermediate dimer cation state and visualize the contraction of the nuclear structure on the femtosecond time scale

Desmoglein autoantibodies and disease severity in pemphigus patients – correlations and discrepancies

Aim: To assess the correlation between the levels of anti-desmoglein-1 and anti-desmoglein-3 autoantibodies and disease severity in pemphigus patients. Materials and methods: Thirty-eight pemphigus patients aged 30 to 87 years were included in the study. All patients underwent clinical examination, pemphigus disease zone index assessment, histopathological and direct immunofluorescence tests, and assessment of desmoglein-1 and desmoglein-3 autoantibodies by enzyme-linked immunosorbent assay. Results: Twenty-eight out of 38 serum samples exceeded the cut-off value of anti-desmoglein-1, and 26 of 38 sera had positive anti-desmoglein-3 antibodies. One serum from 38 controls had positive anti-desmoglein-1 antibodies. Seven (18.4%) patients experienced a mild course of the disease, 16 (42.1%) patients experienced moderate, and 15 (39.5%) patients suffered from severe pemphigus. A significant correlation between disease severity and both autoantibody levels was observed, but there were exceptions. Conclusions: There is a significant correlation between anti-desmoglein antibodies and disease severity in the entire group, but there are also discrepancies in some cases

webPIPSA: a web server for the comparison of protein interaction properties

Protein molecular interaction fields are key determinants of protein functionality. PIPSA (Protein Interaction Property Similarity Analysis) is a procedure to compare and analyze protein molecular interaction fields, such as the electrostatic potential. PIPSA may assist in protein functional assignment, classification of proteins, the comparison of binding properties and the estimation of enzyme kinetic parameters. webPIPSA is a web server that enables the use of PIPSA to compare and analyze protein electrostatic potentials. While PIPSA can be run with downloadable software (see http://projects.eml.org/mcm/software/pipsa), webPIPSA extends and simplifies a PIPSA run. This allows non-expert users to perform PIPSA for their protein datasets. With input protein coordinates, the superposition of protein structures, as well as the computation and analysis of electrostatic potentials, is automated. The results are provided as electrostatic similarity matrices from an all-pairwise comparison of the proteins which can be subjected to clustering and visualized as epograms (tree-like diagrams showing electrostatic potential differences) or heat maps. webPIPSA is freely available at: http://pipsa.eml.org

Natural climate solutions

Our thanks for inputs by L. Almond, A. Baccini, A. Bowman, S. CookPatton, J. Evans, K. Holl, R. Lalasz, A. Nassikas, M. Spalding, M. Wolosin, and expert elicitation respondents. Our thanks for datasets developed by the Hansen lab and the NESCent grasslands working group (C. Lehmann, D. Griffith, T. M. Anderson, D. J. Beerling, W. Bond, E. Denton, E. Edwards, E. Forrestel, D. Fox, W. Hoffmann, R. Hyde, T. Kluyver, L. Mucina, B. Passey, S. Pau, J. Ratnam, N. Salamin, B. Santini, K. Simpson, M. Smith, B. Spriggs, C. Still, C. Strömberg, and C. P. Osborne). This study was made possible by funding from the Doris Duke Charitable Foundation. Woodbury was supported in part by USDA-NIFA Project 2011-67003-30205 Data deposition: A global spatial dataset of reforestation opportunities has been deposited on Zenodo (https://zenodo.org/record/883444). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710465114/-/DCSupplemental.Peer reviewedPublisher PD

Tyrosine Kinase Syk Non-Enzymatic Inhibitors and Potential Anti-Allergic Drug-Like Compounds Discovered by Virtual and In Vitro Screening

In the past decade, the spleen tyrosine kinase (Syk) has shown a high potential for the discovery of new treatments for inflammatory and autoimmune disorders. Pharmacological inhibitors of Syk catalytic site bearing therapeutic potential have been developed, with however limited specificity towards Syk. To address this topic, we opted for the design of drug-like compounds that could impede the interaction of Syk with its cellular partners while maintaining an active kinase protein. To achieve this challenging task, we used the powerful potential of intracellular antibodies for the modulation of cellular functions in vivo, combined to structure-based in silico screening. In our previous studies, we reported the anti-allergic properties of the intracellular antibody G4G11. With the aim of finding functional mimics of G4G11, we developed an Antibody Displacement Assay and we isolated the drug-like compound C-13, with promising in vivo anti-allergic activity. The likely binding cavity of this compound is located at the close vicinity of G4G11 epitope, far away from the catalytic site of Syk. Here we report the virtual screen of a collection of 500,000 molecules against this new cavity, which led to the isolation of 1000 compounds subsequently evaluated for their in vitro inhibitory effects using the Antibody Displacement Assay. Eighty five compounds were selected and evaluated for their ability to inhibit the liberation of allergic mediators from mast cells. Among them, 10 compounds inhibited degranulation with IC50 values ≤10 µM. The most bioactive compounds combine biological activity, significant inhibition of antibody binding and strong affinity for Syk. Moreover, these molecules show a good potential for oral bioavailability and are not kinase catalytic site inhibitors. These bioactive compounds could be used as starting points for the development of new classes of non-enzymatic inhibitors of Syk and for drug discovery endeavour in the field of inflammation related disorders

Optimizing land use decision-making to sustain Brazilian agricultural profits, biodiversity and ecosystem services

AbstractDesigning landscapes that can meet human needs, while maintaining functioning ecosystems, is essential for long-term sustainability. To achieve this goal, we must better understand the trade-offs and thresholds in the provision of ecosystem services and economic returns. To this end, we integrate spatially explicit economic and biophysical models to jointly optimize agricultural profit (sugarcane production and cattle ranching), biodiversity (bird and mammal species), and freshwater quality (nitrogen, phosphorus, and sediment retention) in the Brazilian Cerrado. We generate efficiency frontiers to evaluate the economic and environmental trade-offs and map efficient combinations of agricultural land and natural habitat under varying service importance. To assess the potential impact of the Brazilian Forest Code (FC), a federal policy that aims to promote biodiversity and ecosystem services on private lands, we compare the frontiers with optimizations that mimic the habitat requirements in the region. We find significant opportunities to improve both economic and environmental outcomes relative to the current landscape. Substantial trade-offs between biodiversity and water quality exist when land use planning targets a single service, but these trade-offs can be minimized through multi-objective planning. We also detect non-linear profit-ecosystem services relationships that result in land use thresholds that coincide with the FC requirements. Further, we demonstrate that landscape-level planning can greatly improve the performance of the FC relative to traditional farm-level planning. These findings suggest that through joint planning for economic and environmental goals at a landscape-scale, Brazil's agricultural sector can expand production and meet regulatory requirements, while maintaining biodiversity and ecosystem service provision