Remark on lattice BRST invariance

A recently claimed resolution to the lattice Gribov problem in the context of chiral lattice gauge theories is examined. Unfortunately, I find that the old problem remains.Comment: 4 pages, plain TeX, presentation improved (see acknowledgments

Effects of cryo-EM cooling on structural ensembles

Structure determination by cryo electron microscopy (cryo-EM) provides information on structural heterogeneity and ensembles at atomic resolution. To obtain cryo-EM images of macromolecules, the samples are first rapidly cooled down to cryogenic temperatures. To what extent the structural ensemble is perturbed during cooling is currently unknown. Here, to quantify the effects of cooling, we combined continuum model calculations of the temperature drop, molecular dynamics simulations of a ribosome complex before and during cooling with kinetic models. Our results suggest that three effects markedly contribute to the narrowing of the structural ensembles: thermal contraction, reduced thermal motion within local potential wells, and the equilibration into lower free-energy conformations by overcoming separating free-energy barriers. During cooling, barrier heights below 10 kJ/mol were found to be overcome, which is expected to reduce B-factors in ensembles imaged by cryo-EM. Our approach now enables the quantification of the heterogeneity of room-temperature ensembles from cryo-EM structures

Active role of elongation factor G in maintaining the mRNA reading frame during translation.

During translation, the ribosome moves along the mRNA one codon at a time with the help of elongation factor G (EF-G). Spontaneous changes in the translational reading frame are extremely rare, yet how the precise triplet-wise step is maintained is not clear. Here, we show that the ribosome is prone to spontaneous frameshifting on mRNA slippery sequences, whereas EF-G restricts frameshifting. EF-G helps to maintain the mRNA reading frame by guiding the A-site transfer RNA during translocation due to specific interactions with the tip of EF-G domain 4. Furthermore, EF-G accelerates ribosome rearrangements that restore the ribosome's control over the codon-anticodon interaction at the end of the movement. Our data explain how the mRNA reading frame is maintained during translation

The Phase Diagram and Spectrum of Gauge-Fixed Abelian Lattice Gauge Theory

We consider a lattice discretization of a covariantly gauge-fixed abelian gauge theory. The gauge fixing is part of the action defining the theory, and we study the phase diagram in detail. As there is no BRST symmetry on the lattice, counterterms are needed, and we construct those explicitly. We show that the proper adjustment of these counterterms drives the theory to a new type of phase transition, at which we recover a continuum theory of (free) photons. We present both numerical and (one-loop) perturbative results, and show that they are in good agreement near this phase transition. Since perturbation theory plays an important role, it is important to choose a discretization of the gauge-fixing action such that lattice perturbation theory is valid. Indeed, we find numerical evidence that lattice actions not satisfying this requirement do not lead to the desired continuum limit. While we do not consider fermions here, we argue that our results, in combination with previous work, provide very strong evidence that this new phase transition can be used to define abelian lattice chiral gauge theories.Comment: 42 pages, 30 figure

The dust morphology of the elliptical Galaxy M86 with SPIRE

We present Herschel-SPIRE observations at 250–500 μm of the giant elliptical galaxy M 86 and examine the distribution of the resolved cold dust emission and its relation with other galactic tracers. The SPIRE images reveal three dust components: emission from the central region; a dust lane extending north-south; and a bright emission feature 10 kpc to the south-east. We estimate that ~10^6 M_☉ of dust is spatially coincident with atomic and ionized hydrogen, originating from stripped material from the nearby spiral NGC 4438 due to recent tidal interactions with M 86. The gas-to-dust ratio of the cold gas component ranges from ~20–80. We discuss the different heating mechanisms for the dust features

SPIRE imaging of M 82: Cool dust in the wind and tidal streams

M 82 is a unique representative of a whole class of galaxies, starbursts with superwinds, in the Very Nearby Galaxy Survey with Herschel. In addition, its interaction with the M 81 group has stripped a significant portion of its interstellar medium from its disk. SPIRE maps now afford better characterization of the far-infrared emission from cool dust outside the disk, and sketch a far more complete picture of its mass distribution and energetics than previously possible. They show emission coincident in projection with the starburst wind and in a large halo, much more extended than the PAH band emission seen with Spitzer. Some complex substructures coincide with the brightest PAH filaments, and others with tidal streams seen in atomic hydrogen. We subtract the far-infrared emission of the starburst and underlying disk from the maps, and derive spatially-resolved far-infrared colors for the wind and halo. We interpret the results in terms of dust mass, dust temperature, and global physical conditions. In particular, we examine variations in the dust physical properties as a function of distance from the center and the wind polar axis, and conclude that more than two thirds of the extraplanar dust has been removed by tidal interaction, and not entrained by the starburst wind

The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons

Atomistic simulations of the human proteasome inhibited by a covalent ligand

The proteasome is a large biomolecular complex responsible for protein degradation. It is under intense research due to its fundamental role in cellular homeostasis, and tremendous potential for medicinal applications. Recent data from X-ray crystallography and cryo-electron microscopy have suggested that there is a large-scale structural change upon binding of an inhibitor. We carried out atomistic molecular dynamics simulations of the native and inhibited proteasomes to understand the molecular details of the inhibition. Here we describe the technical details of the simulations and assess the quality of the trajectories obtained. The biochemical aspects of the proteasome are under further investigation and will be published elsewhere. This work was a part of the GCS-Prot project at the HLRS, run on the Cray XC40 supercomputing system

Molecular simulations of the ribosome and associated translation factors

The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM), the structure of the ribosome was resolved at atomic resolution in many functional and conformational states. Molecular dynamics simulations have added information on dynamics and energetics to the available structural information, thereby have bridged the gap to the kinetics obtained from single-molecule and bulk experiments. Here, we review recent computational studies that brought notable insights into ribosomal structure and function