The BR-body proteome contains a complex network of protein-protein and protein-RNA interactions.

Bacterial RNP bodies (BR-bodies) are non-membrane-bound structures that facilitate mRNA decay by concentrating mRNA substrates with RNase E and the associated RNA degradosome machinery. However, the full complement of proteins enriched in BR-bodies has not been defined. Here we define the protein components of BR-bodies through enrichment of the bodies followed by mass spectrometry-based proteomic analysis. We found 111 BR-body enriched proteins, including several RNA binding proteins, many of which are also recruited directly to in vitro reconstituted RNase E droplets, showing BR-bodies are more complex than previously assumed. While most BR-body enriched proteins that were tested cannot phase separate, we identified five that undergo RNA-dependent phase separation in vitro, showing other RNP condensates interface with BR-bodies. RNA degradosome protein clients are recruited more strongly to RNase E droplets than droplets of other RNP condensates, implying that client specificity is largely achieved through direct protein-protein interactions. We observe that some RNP condensates assemble with preferred directionally, suggesting that RNA may be trafficked through RNP condensates in an ordered manner to facilitate mRNA processing/decay, and that some BR-body associated proteins have the capacity to dissolve the condensate. Finally, we find that RNA dramatically stimulates the rate of RNase E phase separation in vitro, explaining the dissolution of BR-bodies after cellular mRNA depletion observed previously. Altogether, these results suggest that a complex network of protein-protein and protein-RNA interactions controls BR-body phase separation and RNA processing.

Rapid measurement of the low contrast detectability of CT scanners.

PURPOSE: Low contrast detectability (LCD) is a metric of fundamental importance in computed tomography (CT) imaging. In spite of this, its measurement is challenging in the context of nonlinear data processing. We introduce a new framework for objectively characterizing LCD with a single scan of a special-purpose phantom and automated analysis software. The output of the analysis software is a "machine LCD" metric which is more representative of LCD than contrast-noise ratio (CNR). It is not intended to replace human observer or model observer studies. METHODS: Following preliminary simulations, we fabricated a phantom containing hundreds of low-contrast beads. These beads are acrylic spheres (1.6 mm, net contrast ~10 HU) suspended and randomly dispersed in a background matrix of nylon pellets and isoattenuating saline. The task was to search for and localize the beads. A modified matched filter was used to automatically scan the reconstruction and select candidate bead localizations of varying confidence. These were compared to bead locations as determined from a high-dose reference scan to produce free-response ROC curves. We compared iterative reconstruction (IR) and filtered backpropagation (FBP) at multiple dose levels between 40 and 240 mAs. The scans at 60, 120, and 180 mAs were performed three times each to estimate uncertainty. RESULTS: Experimental scans demonstrated the feasibility of our technique. Our metric for machine LCD was the area under the exponential transform of the FROC curve (AUC). AUC increased monotonically from 0.21 at 40 mAs to 0.84 at 240 mAs. The sample standard deviation of AUC was approximately 0.02. This measurement uncertainty in AUC corresponded to a change in tube current of 4% to 8%. Surprisingly, we found that AUCs for IR were slightly worse than AUCs for FBP. While the phantom was sufficient for these experiments, it contained small air bubbles and alternative fabrication methods will be necessary for widespread utilization. CONCLUSIONS: It is feasible to measure machine LCD using a search task on a phantom with hundreds of beads and to obtain tight error bars using only a single scan. Our method could facilitate routine quality assurance or possibly enable comparisons between different protocols and scanners.

CT metal artifact reduction algorithms: Toward a framework for objective performance assessment.

PURPOSE: Although several metal artifact reduction (MAR) algorithms for computed tomography (CT) scanning are commercially available, no quantitative, rigorous, and reproducible method exists for assessing their performance. The lack of assessment methods poses a challenge to regulators, consumers, and industry. We explored a phantom-based framework for assessing an important aspect of MAR performance: how applying MAR in the presence of metal affects model observer performance at a low-contrast detectability (LCD) task This work is, to our knowledge, the first model observer-based framework for the evaluation of MAR algorithms in the published literature. METHODS: We designed a numerical head phantom with metal implants. In order to incorporate an element of randomness, the phantom included a rotatable inset with an inhomogeneous background. We generated simulated projection data for the phantom. We applied two variants of a simple MAR algorithm, sinogram inpainting, to the projection data, that we reconstructed using filtered backprojection. To assess how MAR affected observer performance, we examined the detectability of a signal at the center of a region of interest (ROI) by a channelized Hotelling observer (CHO). As a figure of merit, we used the area under the ROC curve (AUC). RESULTS: We used simulation to test our framework on two variants of the MAR technique of sinogram inpainting. We found that our method was able to resolve the difference in two different MAR algorithms' effect on LCD task performance, as well as the difference in task performances when MAR was applied, vs not. CONCLUSION: We laid out a phantom-based framework for objective assessment of how MAR impacts low-contrast detectability, that we tested on two MAR algorithms. Our results demonstrate the importance of testing MAR performance over a range of object and imaging parameters, since applying MAR does not always improve the quality of an image for a given diagnostic task. Our framework is an initial step toward developing a more comprehensive objective assessment method for MAR, which would require developing additional phantoms and methods specific to various clinical applications of MAR, and increasing study efficiency.

Objective assessment of image quality and dose reduction in CT iterative reconstruction.

PURPOSE: Iterative reconstruction (IR) algorithms have the potential to reduce radiation dose in CT diagnostic imaging. As these algorithms become available on the market, a standardizable method of quantifying the dose reduction that a particular IR method can achieve would be valuable. Such a method would assist manufacturers in making promotional claims about dose reduction, buyers in comparing different devices, physicists in independently validating the claims, and the United States Food and Drug Administration in regulating the labeling of CT devices. However, the nonlinear nature of commercially available IR algorithms poses challenges to objectively assessing image quality, a necessary step in establishing the amount of dose reduction that a given IR algorithm can achieve without compromising that image quality. This review paper seeks to consolidate information relevant to objectively assessing the quality of CT IR images, and thereby measuring the level of dose reduction that a given IR algorithm can achieve. METHODS: The authors discuss task-based methods for assessing the quality of CT IR images and evaluating dose reduction. RESULTS: The authors explain and review recent literature on signal detection and localization tasks in CT IR image quality assessment, the design of an appropriate phantom for these tasks, possible choices of observers (including human and model observers), and methods of evaluating observer performance. CONCLUSIONS: Standardizing the measurement of dose reduction is a problem of broad interest to the CT community and to public health. A necessary step in the process is the objective assessment of CT image quality, for which various task-based methods may be suitable. This paper attempts to consolidate recent literature that is relevant to the development and implementation of task-based methods for the assessment of CT IR image quality.

Observing Zitterbewegung with ultracold atoms.

We propose an optical lattice scheme which would permit the experimental observation of Zitterbewegung (ZB) with ultracold, neutral atoms. A four-level tripod variant of the setup for stimulated Raman adiabatic passage (STIRAP) has previously been proposed for generating non-Abelian gauge fields. Dirac-like Hamiltonians, which exhibit ZB, are simple examples of such non-Abelian gauge fields; we show how a variety of them can arise, and how ZB can be observed, in a tripod system. We predict that the ZB should occur at experimentally accessible frequencies and amplitudes.

Spin field effect transistors with ultracold atoms.

We propose a method of constructing cold atom analogs of the spintronic device known as the Datta-Das transistor (DDT), which, despite its seminal conceptual role in spintronics, has never been successfully realized with electrons. We propose two alternative schemes for an atomic DDT, both of which are based on the experimental setup for tripod stimulated Raman adiabatic passage. Both setups involve atomic beams incident on a series of laser fields mimicking the relativistic spin-orbit coupling for electrons that is the operating mechanism of the DDT.

Front propagation of spatiotemporal chaos.

We study the dynamics of the front separating a spatiotemporally chaotic region from a stable steady region using a simple model applicable to periodically forced systems. In particular, we investigate both the coarsening of the front induced by the inherent "noise" of the chaotic region, and the long wavelength dynamics causing the front to develop cusps.

Combined activity of metronidazole and gentamicin on Bacteroides fragilis in vivo and in vitro.

A mixed aerobic/anaerobic infection in mice was established by co-injecting Bacteroides fragilis and Escherichia coli into a thigh muscle. Metronidazole administration 6 h after this inoculation resulted in a dose-dependent decrease of Bact. fragilis at 18 h after drug administration. Co-administration of gentamicin with metronidazole resulted in a significant decrease of the numbers of E. coli but did not markedly influence the effect of metronidazole on Bact. fragilis.

Efficacy of amoxycillin and benzylpenicillin combined with clavulanic acid against Bacteroides fragilis in vitro and in experimentally infected mice.

Because the insensitivity of Bacteroides fragilis to penicillins is due to betalactamase formation, the potentiating effect of the betalactamase inhibitor clavulanic acid on the action of amoxycillin and benzylpenicillin against this bacterium was studied in vitro and in an experimental infection in mice. The addition of clavulanic acid to amoxycillin and benzylpenicillin resulted in a marked synergistic effect against B. fragilis, as assessed by both MIC determinations and in 4-h growth curves. In the experimental infection, where co-inoculation with Escherichia coli was obligatory for the outgrowth of B. fragilis, both penicillins had a dose-dependent effect on both species. However, the addition of clavulanic acid to amoxycillin and benzylpenicillin did not increase the effect of the penicillins against B. fragilis or against E. coli. Because a synergistic effect might have remained undetected in vivo, the experimental conditions were varied, i.e. the drugs were administered in the proliferation phase of B. fragilis, the clavulanic acid to betalactam ratios were varied, and the drugs were given after inoculation of B. fragilis in which betalactamase production has been induced. However, even after variation of the experimental conditions the addition of clavulanic acid to benzylpenicillin did not result in a potentiation of the effect of benzylpenicillin against B. fragilis.

Relative antibacterial efficacy of clindamycin and metronidazole against Bacteroides fragilis in vitro and in experimentally infected mice.

The antibacterial activity of clindamycin and metronidazole against Bacteroides fragilis was quantitated in vitro by MIC determination and colony counting at 24 h and in vivo from the effects on an experimental B. fragilis infection in mice; this infection was established after co-inoculation of B. fragilis and Escherichia coli. In vitro, clindamycin was 8 to 16 times more effective than metronidazole in terms of MIC values, and more than 30 times according to colony counts at 24 h. In vivo clindamycin was almost 8 times less effective than metronidazole according to dose. This was partly due to its less favorable pharmacokinetic properties, but clindamycin was still only 1.6 times more effective than metronidazole according to free plasma concentrations. In vivo neither clindamycin nor metronidazole had any antibacterial effect against E. coli. The discrepancy between the in vivo and in vitro results for B. fragilis is discussed.