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  1. Siegel (Ed.)
    Intestinal microbiota confers susceptibility to diet-induced obesity yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, however the underlying mechanisms are unclear. We monocolonized germ-free (GF) mice with a widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) under trp-free or -sufficient dietary conditions. We obtained untargeted metabolomics from the mouse feces and serum using liquid chromatography-mass spectrometry and obtained intestinal transcriptomic profiles via bulk-RNA sequencing. When comparing LGG-monocolonized mice with GF mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and -oxidation. Upregulation was specific and was not observed in transcriptomes of trp-fed conventional mice and mice monocolonized with Ruminococcus gnavus. Metabolomics showed that fecal and serum metabolites were also modified by LGG-host-trp interaction. We developed an R-Script based MEtabolome-TRanscriptome Correlation Analysis (METRCA) algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and -oxidation gene networks. This high throughput metabolome-transcriptome correlation strategy can be used in similar investigations to reveal potential interactions between specific metabolites and functional or disease-related transcriptomic networks. 
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    Free, publicly-accessible full text available April 1, 2025
  2. Kaestner Pack (Ed.)
    BACKGROUND & AIMS: Lacticaseibacillus rhamnosus GG (LGG) is the world’s most consumed probiotic species but its mechanism of action on intestinal permeability and differentiation as well as its interactions with an essential source of signaling metabolites, dietary tryptophan, are incompletely studied. METHODS: Untargeted metabolomic and transcriptomic analysis were performed for LGG mono-colonized germ-free (GF) mice fed with tryptophan (trp)-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations were performed using a newly developed metabolome-transcriptome correlating bioinformatic algorism. Newly uncovered gut barrier-modulating metabolites whose abundances are regulated by LGG and dietary trp were functionally tested in Trans-Epithelial Electrical Resistance (TEER) assay, mouse enteroid, and dextran sulfate sodium (DSS) experimental colitis. The contribution of trp-methylnicotinamide (MNA) pathway to barrier protection is delineated at specific tight junction (TJ) proteins and enterocyte-promoting factors with gain and loss of function approaches. RESULTS: LGG, strictly in the presence of dietary trp, promotes the enterocyte program and the expression of multiple TJ genes, particularly Ocln. Fecal and serum metabolites that are synergistically stimulated by LGG and dietary trp are identified. Functional evaluations revealed a novel LGG-stimulated trp-dependent Vitamin B3 metabolism pathway, with MNA unexpectedly being the most robust barrier-protective metabolite in vitro and in vivo. Reduced serum MNA is significantly associated with increased disease activity in IBD patients. Exogenous MNA enhances gut barrier in homeostasis and robustly promotes colonic healing in DSS colitis. MNA is sufficient to promote intestinal epithelial Ocln and RNF43, a master inhibitor of Wnt pathway. Blocking trp or Vitamin B3 absorption abolishes barrier recovery in vivo. CONCLUSIONS: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects gut barrier against colitis. 
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    Free, publicly-accessible full text available April 1, 2025
  3. Free, publicly-accessible full text available December 26, 2024

    The spectral element method is currently the method of choice for computing accurate synthetic seismic wavefields in realistic 3-D earth models at the global scale. However, it requires significantly more computational time, compared to normal mode-based approximate methods. Source stacking, whereby multiple earthquake sources are aligned on their origin time and simultaneously triggered, can reduce the computational costs by several orders of magnitude. We present the results of synthetic tests performed on a realistic radially anisotropic 3-D model, slightly modified from model SEMUCB-WM1 with three component synthetic waveform ‘data’ for a duration of 10 000 s, and filtered at periods longer than 60 s, for a set of 273 events and 515 stations. We consider two definitions of the misfit function, one based on the stacked records at individual stations and another based on station-pair cross-correlations of the stacked records. The inverse step is performed using a Gauss–Newton approach where the gradient and Hessian are computed using normal mode perturbation theory. We investigate the retrieval of radially anisotropic long wavelength structure in the upper mantle in the depth range 100–800 km, after fixing the crust and uppermost mantle structure constrained by fundamental mode Love and Rayleigh wave dispersion data. The results show good performance using both definitions of the misfit function, even in the presence of realistic noise, with degraded amplitudes of lateral variations in the anisotropic parameter ξ. Interestingly, we show that we can retrieve the long wavelength structure in the upper mantle, when considering one or the other of three portions of the cross-correlation time series, corresponding to where we expect the energy from surface wave overtone, fundamental mode or a mixture of the two to be dominant, respectively. We also considered the issue of missing data, by randomly removing a successively larger proportion of the available synthetic data. We replace the missing data by synthetics computed in the current 3-D model using normal mode perturbation theory. The inversion results degrade with the proportion of missing data, especially for ξ, and we find that a data availability of 45 per cent or more leads to acceptable results. We also present a strategy for grouping events and stations to minimize the number of missing data in each group. This leads to an increased number of computations but can be significantly more efficient than conventional single-event-at-a-time inversion. We apply the grouping strategy to a real picking scenario, and show promising resolution capability despite the use of fewer waveforms and uneven ray path distribution. Source stacking approach can be used to rapidly obtain a starting 3-D model for more conventional full-waveform inversion at higher resolution, and to investigate assumptions made in the inversion, such as trade-offs between isotropic, anisotropic or anelastic structure, different model parametrizations or how crustal structure is accounted for.

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  5. Andrew Yeh-Ching Nee, editor-ion-chief (Ed.)
    Wire arc additive manufacturing (WAAM) has received increasing use in 3D printing because of its high deposition rates suitable for components with large and complex geometries. However, the lower forming accuracy of WAAM than other metal additive manufacturing methods has imposed limitations on manufacturing components with high precision. To resolve this issue, we herein implemented the hybrid manufacturing (HM) technique, which integrated WAAM and subtractive manufacturing (via a milling process), to attain high forming accuracy while taking advantage of both WAAM and the milling process. We describe in this paper the design of a robot-based HM platform in which the WAAM and CNC milling are integrated using two robotic arms: one for WAAM and the other for milling immediately following WAAM. The HM was demonstrated with a thin-walled aluminum 5356 component, which was inspected by X-ray micro-computed tomography (μCT) for porosity visualization. The temperature and cutting forces in the component under milling were acquired for analysis. The surface roughness of the aluminum component was measured to assess the surface quality. In addition, tensile specimens were cut from the components using wire electrical discharge machining (WEDM) for mechanical testing. Both machining quality and mechanical properties were found satisfactory; thus the robot-based HM platform was shown to be suitable for manufacturing high-quality aluminum parts. 
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    Free, publicly-accessible full text available October 24, 2024
  6. Free, publicly-accessible full text available October 1, 2024
  7. Free, publicly-accessible full text available August 31, 2024
  8. Free, publicly-accessible full text available August 31, 2024
  9. Free, publicly-accessible full text available August 1, 2024
  10. Free, publicly-accessible full text available August 1, 2024