Extreme accumulation of nucleotides in simulated hydrothermal pore systems

We simulate molecular transport in elongated hydrothermal pore systems influenced by a thermal gradient. We find extreme accumulation of molecules in a wide variety of plugged pores. The mechanism is able to provide highly concentrated single nucleotides, suitable for operations of an RNA world at the origin of life. It is driven solely by the thermal gradient across a pore. On the one hand, the fluid is shuttled by thermal convection along the pore, whereas on the other hand, the molecules drift across the pore, driven by thermodiffusion. As a result, millimeter-sized pores accumulate even single nucleotides more than 108-fold into micrometer-sized regions. The enhanced concentration of molecules is found in the bulk water near the closed bottom end of the pore. Because the accumulation depends exponentially on the pore length and temperature difference, it is considerably robust with respect to changes in the cleft geometry and the molecular dimensions. Whereas thin pores can concentrate only long polynucleotides, thicker pores accumulate short and long polynucleotides equally well and allow various molecular compositions. This setting also provides a temperature oscillation, shown previously to exponentially replicate DNA in the protein-assisted PCR. Our results indicate that, for life to evolve, complicated active membrane transport is not required for the initial steps. We find that interlinked mineral pores in a thermal gradient provide a compelling high-concentration starting point for the molecular evolution of life

The seven-gluon amplitude in multi-Regge kinematics beyond leading logarithmic accuracy

We present an all-loop dispersion integral, well-defined to arbitrary logarithmic accuracy, describing the multi-Regge limit of the 2->5 amplitude in planar N=4 super Yang-Mills theory. It follows from factorization, dual conformal symmetry and consistency with soft limits, and specifically holds in the region where the energies of all produced particles have been analytically continued. After promoting the known symbol of the 2-loop N-particle MHV amplitude in this region to a function, we specialize to N=7, and extract from it the next-to-leading order (NLO) correction to the BFKL central emission vertex, namely the building block of the dispersion integral that had not yet appeared in the well-studied six-gluon case. As an application of our results, we explicitly compute the seven-gluon amplitude at next-to-leading logarithmic accuracy through 5 loops for the MHV case, and through 3 and 4 loops for the two independent NMHV helicity configurations, respectively.Comment: 56 pages, 4 figures, 1 table; v2: minor corrections and clarifications, matches published versio

From Lagrangians to Events: Computer Tutorial at the MC4BSM-2012 Workshop

This is a written account of the computer tutorial offered at the Sixth MC4BSM workshop at Cornell University, March 22-24, 2012. The tools covered during the tutorial include: FeynRules, LanHEP, MadGraph, CalcHEP, Pythia 8, Herwig++, and Sherpa. In the tutorial, we specify a simple extension of the Standard Model, at the level of a Lagrangian. The software tools are then used to automatically generate a set of Feynman rules, compute the invariant matrix element for a sample process, and generate both parton-level and fully hadronized/showered Monte Carlo event samples. The tutorial is designed to be self-paced, and detailed instructions for all steps are included in this write-up. Installation instructions for each tool on a variety of popular platforms are also provided.Comment: 58 pages, 1 figur

Designer lipid-like peptides

A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins

Insertion of T4-lysozyme (T4L) can be a useful tool for studying olfactory-related GPCRs.

The detergents used to solubilize GPCRs can make crystal growth the rate-limiting step in determining their structure. The Kobilka laboratory showed that insertion of T4-lysozyme (T4L) in the 3rd intracellular loop is a promising strategy towards increasing the solvent-exposed receptor area, and hence the number of possible lattice-forming contacts. The potential to use T4L with the olfactory-related receptors hOR17-4 and hVN1R1 was thus tested. The structure and function of native and T4L-variants were compared. Both receptors localized to the cell membrane, and could initiate ligand-activated signaling. Purified receptors not only had the predicted alpha-helical structures, but also bound their ligands canthoxal (MW = 178.23) and myrtenal (MW = 150.22). Interestingly, the T4L variants had higher percentages of soluble monomers compared to protein aggregates, effectively increasing the protein yield that could be used for structural and function studies. They also bound their ligands for longer times, suggesting higher receptor stability. Our results indicate that a T4L insertion may be a general method for obtaining GPCRs suitable for structural studies

Color-dressed recursive relations for multi-parton amplitudes

Remarkable progress inspired by twistors has lead to very simple analytic expressions and to new recursive relations for multi-parton color-ordered amplitudes. We show how such relations can be extended to include color and present the corresponding color-dressed formulation for the Berends-Giele, BCF and a new kind of CSW recursive relations. A detailed comparison of the numerical efficiency of the different approaches to the calculation of multi-parton cross sections is performed.Comment: 31 pages, 4 figures, 6 table

A Robust and Rapid Method of Producing Soluble, Stable, and Functional G-Protein Coupled Receptors

Membrane proteins, particularly G-protein coupled receptors (GPCRs), are notoriously difficult to express. Using commercial E.coli cell-free systems with the detergent Brij-35, we could rapidly produce milligram quantities of 13 unique GPCRs. Immunoaffinity purification yielded receptors at >90% purity. Secondary structure analysis using circular dichroism indicated that the purified receptors were properly folded. Microscale thermophoresis, a novel label-free and surface-free detection technique that uses thermal gradients, showed that these receptors bound their ligands. The secondary structure and ligand-binding results from cell-free produced proteins were comparable to those expressed and purified from HEK293 cells. Our study demonstrates that cell-free protein production using commercially available kits and optimal detergents is a robust technology that can be used to produce sufficient GPCRs for biochemical, structural, and functional analyses. This robust and simple method may further stimulate others to study the structure and function of membrane proteins.United States. Defense Advanced Research Projects Agency (DARPA-HR0011-09-C-0012)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra