OMx-D: semiempirical methods with orthogonalization and dispersion corrections. Implementation and biochemical application

The semiempirical methods of the OMx family (orthogonalization models OM1, OM2, and OM3) are known to describe biochemical systems more accurately than standard semiempirical approaches such as AM1. We investigate the benefits of augmenting these methods with an empirical dispersion term (OMx-D) taken from recent density functional work, without modifying the standard OMx parameters. Significant improvements are achieved for non-covalent interactions, with mean unsigned errors of 1.41 kcal/mol (OM2-D) and 1.31 kcal/mol (OM3-D) for the binding energy of the complexes in the JSCH-2005 data base. This supports the use of these augmented methods in quantum mechanical/molecular mechanical (QM/MM) studies of biomolecules, for example during system preparation and equilibration. As an illustrative application, we present QM and QM/MM calculations on the binding between antibody 34E4 and a hapten, where OM3-D performs better than the methods without dispersion terms (AM1, OM3)

Arecibo Multi-Epoch HI Absorption Measurements Against Pulsars: Tiny-Scale Atomic Structure

We present results from multi-epoch neutral hydrogen (HI) absorption observations of six bright pulsars with the Arecibo telescope. Moving through the interstellar medium (ISM) with transverse velocities of 10--150 AU/yr, these pulsars have swept across 1--200 AU over the course of our experiment, allowing us to probe the existence and properties of the tiny scale atomic structure (TSAS) in the cold neutral medium (CNM). While most of the observed pulsars show no significant change in their HI absorption spectra, we have identified at least two clear TSAS-induced opacity variations in the direction of B1929+10. These observations require strong spatial inhomogeneities in either the TSAS clouds' physical properties themselves or else in the clouds' galactic distribution. While TSAS is occasionally detected on spatial scales down to 10 AU, it is too rare to be characterized by a spectrum of turbulent CNM fluctuations on scales of 10-1000 AU, as previously suggested by some work. In the direction of B1929+10, an apparent correlation between TSAS and interstellar clouds inside the warm Local Bubble (LB) indicates that TSAS may be tracing the fragmentation of the LB wall via hydrodynamic instabilities. While similar fragmentation events occur frequently throughout the ISM, the warm medium surrounding these cold cloudlets induces a natural selection effect wherein small TSAS clouds evaporate quickly and are rare, while large clouds survive longer and become a general property of the ISM.Comment: 21 pages, 13 figures, accepted by Ap

Bonded Invar Clip Removal Using Foil Heaters

A new process uses local heating and temperature monitoring to soften the adhesive under Invar clips enough that they can be removed without damaging the composite underneath or other nearby bonds. Two 1x1 in. (approx.2.5x2.5 cm), 10-W/sq in. (approx.1.6-W/sq cm), 80-ohm resistive foil Kapton foil heaters, with pressure-sensitive acrylic adhesive backing, are wired in parallel to a 50-V, 1-A limited power supply. At 1 A, 40 W are applied to the heater pair. The temperature is monitored in the clip radius and inside the tube, using a dual thermocouple readout. Several layers of aluminum foil are used to speed the heat up, allowing clips to be removed in less than five minutes. The very local heating via the foil heaters allows good access for clip removal and protects all underlying and adjacent materials

Using a Cold Radiometer to Measure Heat Loads and Survey Heat Leaks

We have developed an inexpensive cold radiometer for use in thermal/vacuum chambers to measure heat loads, characterize emissivity and specularity of surfaces and to survey areas to evaluate stray heat loads. We report here the results of two such tests for the James Webb Space Telescope to measure heat loads and effective emissivities of 2 major pieces of optical ground support equipment that will be used in upcoming thermal vacuum testing of the Telescope

CHARMM force field parameterization protocol for self-assembling peptide amphiphiles : the Fmoc moiety

Aromatic peptide amphiphiles are known to self-assemble into nanostructures but the molecular level structure and the mechanism of formation of these nanostructures is not yet understood in detail. Molecular dynamic simulations using the CHARMM force field have been applied to a wide variety of peptide-based systems to obtain molecular level details of processes that are inaccessible with experimental techniques. However, this force field does not include parameters for the aromatic moieties which dictate the self-assembly of these systems. The standard CHARMM force field parameterization protocol uses hydrophilic interactions for the non-bonding parameters evaluation. However, to effectively reproduce the self-assembling behaviour of these molecules, the balance between the hydrophilic and hydrophobic nature of the molecule is essential. In this work, a modified parameterization protocol for the CHARMM force field for these aromatic moieties is presented. This protocol is applied for the specific case of the Fmoc moiety. The resulting set of parameters satisfies the conformational and interactions analysis and is able to reproduce experimental results such as the Fmoc-S-OMe water/octanol partition free energy and the self-assembly of Fmoc-S-OH and Fmoc-Y-OH into spherical micelles and fibres, respectively, while also providing detailed information on the mechanism of these processes. The effectiveness of the parameters for the Fmoc moiety validates the protocol as a robust approach to paramterise this class of compounds

Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries

There is a significant interest in the use of unmodified self-assembling peptides as building blocks for functional, supramolecular biomaterials. Recently, dynamic peptide libraries (DPLs) have been proposed to select self-assembling materials from dynamically exchanging mixture of dipeptide inputs in the presence of a nonspecific protease enzyme, where peptide sequences are selected and amplified based on their self-assembling tendencies. It was shown that the results of DPL of mixed sequences (e.g. starting from a mixture of dileucine, L2 and diphenylalanine, F2) did not give the same outcome as the separate L2 and F2 libraries (which give rise to formation of F6 and L6), implying that interaction between these sequences could disrupt the self-assembly. In this study, coarse grained molecular dynamic (CG-MD) simulations are used to understand the DPL results for F2, L2 and mixed libraries. CG-MD simulations demonstrate that interactions between precursors can cause the low formation yield of hexapeptides in mixtures of dipeptides and show that this ability to disrupt is influenced by the concentration of the different species in the DPL. The disrupting self-assembly effect between the species in DPL is an important effect to take into account in dynamic combinatorial chemistry as it affects the possible discovery of new materials. The work shows that combined computational and experimental screening can be used complementary and in combination provide a powerful means to discover new supramolecular peptide nanostructures

Using experimental and computational energy equilibration to understand hierarchical self-assembly of Fmoc-dipeptide amphiphiles

Despite progress, a fundamental understanding of the relationships between the molecular structure and self-assembly configuration of Fmoc-dipeptides is still in its infancy. In this work, we provide a combined experimental and computational approach that makes use of free energy equilibration of a number of related Fmoc-dipeptides to arrive at an atomistic model of Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely related dipeptide sequences are dynamically exchanged to eventually favour the formation of the thermodynamically most stable configuration, the relative importance of C-terminus modifications (amide versus methyl ester) and contributions of aliphatic versus aromatic amino acids (phenylalanine F vs. leucine L) is determined (F > L and NH2 > OMe). The approach enables a comparative interpretation of spectroscopic data, which can then be used to aid the construction of the atomistic model of the most stable structure (Fmoc-TF-NH2). The comparison of the relative stabilities of the models using molecular dynamic simulations and the correlation with experimental data using dynamic peptide libraries and a range of spectroscopy methods (FTIR, CD, fluorescence) allow for the determination of the nanostructure with atomistic resolution. The final model obtained through this process is able to reproduce the experimentally observed formation of intertwining fibres for Fmoc-TF-NH2, providing information of the interactions involved in the hierarchical supramolecular self-assembly. The developed methodology and approach should be of general use for the characterization of supramolecular structures

High-speed GaAs-based resonant-cavity-enhanced 1.3 μm photodetector

Cataloged from PDF version of article.We report GaAs-based high-speed, resonant-cavity-enhanced, Schottky barrier internal photoemissionphotodiodes operating at 1.3 μm. The devices were fabricated by using a microwave-compatible fabrication process. Resonance of the cavity was tuned to 1.3 μm and a nine-fold enhancement was achieved in quantum efficiency. The photodiode had an experimental setup limited temporal response of 16 ps, corresponding to a 3 dB bandwidth of 20 GHz. © 2000 American Institute of Physic

Neutron-Unbound Excited States of 23N

Neutron unbound states in 23N were populated via proton knockout from an 83.4 MeV/nucleon 24O beam on a liquid deuterium target. The two-body decay energy displays two peaks at E1∼100keV and E2∼1MeV with respect to the neutron separation energy. The data are consistent with shell model calculations predicting resonances at excitation energies of ∼3.6MeV and ∼4.5MeV. The selectivity of the reaction implies that these states correspond to the first and second 3/2− states. The energy of the first state is about 1.3 MeV lower than the first excited 2+ in 24O. This decrease is largely due to coupling with the πp−13/2 hole along with a small reduction of the N=16 shell gap in 23N

An enhanced CRISPR repressor for targeted mammalian gene regulation.

The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB-MeCP2, to nuclease-dead Cas9. We demonstrate the system's superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits