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  1. Abstract Bacteroides species are prominent members of the human gut microbiota. The prevalence and stability of Bacteroides in humans make them ideal candidates to engineer as programmable living therapeutics. Here we report a biotic decision-making technology in a community of Bacteroides (consortium transcriptional programming) with genetic circuit compression. Circuit compression requires systematic pairing of engineered transcription factors with cognate regulatable promoters. In turn, we demonstrate the compression workflow by designing, building, and testing all fundamental two-input logic gates dependent on the inputs isopropyl-β-D-1-thiogalactopyranoside and D-ribose. We then deploy complete sets of logical operations in five human donor Bacteroides , with which we demonstrate sequential gain-of-function control in co-culture. Finally, we couple transcriptional programs with CRISPR interference to achieve loss-of-function regulation of endogenous genes—demonstrating complex control over community composition in co-culture. This work provides a powerful toolkit to program gene expression in Bacteroides for the development of bespoke therapeutic bacteria.
    Free, publicly-accessible full text available December 1, 2023
  2. Free, publicly-accessible full text available October 1, 2023
  3. Abstract Pathogen contamination of water has a massive impact on global human health. In particular, viruses pose unique challenges to water treatment techniques due to their small size and presence in water as both individual virions and when absorbed onto larger particles. Low-energy water treatment processes such as media filtration are not capable of completely removing viruses owing to their small size. Hence, less sustainable processes with high chemical or energy consumption such as chemical disinfection, ultraviolet irradiation, and membrane filtration are usually required. To overcome high energy and/or chemical requirements for virus treatment, designs for sustainable fiber filters fabricated from minimally processed natural materials for efficient virus (MS2) and bacteria ( E. coli ) removal are presented in this work. These filters were created by functionalizing readily accessible natural fibers including cotton, silk, and flax with a simple aqueous extract containing cationic proteins from Moringa oleifera seeds. The proposed filters offer a comprehensive low cost, low energy, and low environmental impact solution for pathogen removal from water with removals of >7log 10 (99.99999%) for viruses and bacteria.
    Free, publicly-accessible full text available December 1, 2023
  4. Free, publicly-accessible full text available October 1, 2023
  5. Abstract If G is permutation group acting on a finite set $\Omega $ , then this action induces a natural action of G on the power set $\mathscr{P}(\Omega )$ . The number $s(G)$ of orbits in this action is an important parameter that has been used in bounding numbers of conjugacy classes in finite groups. In this context, $\inf ({\log _2 s(G)}/{\log _2 |G|})$ plays a role, but the precise value of this constant was unknown. We determine it where G runs over all permutation groups not containing any ${{\textrm {A}}}_l, l> 4$ , as a composition factor.
    Free, publicly-accessible full text available August 1, 2023
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  7. Free, publicly-accessible full text available July 1, 2023
  8. To investigate the influence of manganese substitution on the saturation magnetization of manganese ferrite nanoparticles, samples with various compositions (MnxFe3−xO4,x = 0, 0.25, 0.5, 0.75, and 1) were synthesized and characterized. The saturation magnetization of such materials was both calculated using density functional theory and measured via vibrating sample magnetometry. A discrepancy was found; the computational data demonstrated a positive correlation between manganese content and saturation magnetization, while the experimental data exhibited an inverse correlation. X-ray diffraction (XRD) and magnetometry results indicated that the crystallite diameter and the magnetic diameter decrease when adding more manganese, which could explain the loss of magnetization of the particles. For 20 nm nanoparticles, with increasing manganese substitution level, the crystallite size decreases from 10.9 nm to 6.3 nm and the magnetic diameter decreases from 15.1 nm to 3.5 nm. Further high resolution transmission electron microscopy (HRTEM) analysis confirmed the manganese substitution induced defects in the crystal lattice, which encourages us to find ways of eliminating crystalline defects to make more reliable ferrite nanoparticles.
    Free, publicly-accessible full text available August 25, 2023
  9. Jędrzejewska-Szmek, Joanna (Ed.)
    Chemical synapses exhibit a diverse array of internal mechanisms that affect the dynamics of transmission efficacy. Many of these processes, such as release of neurotransmitter and vesicle recycling, depend strongly on activity-dependent influx and accumulation of Ca 2+ . To model how each of these processes may affect the processing of information in neural circuits, and how their dysfunction may lead to disease states, requires a computationally efficient modelling framework, capable of generating accurate phenomenology without incurring a heavy computational cost per synapse. Constructing a phenomenologically realistic model requires the precise characterization of the timing and probability of neurotransmitter release. Difficulties arise in that functional forms of instantaneous release rate can be difficult to extract from noisy data without running many thousands of trials, and in biophysical synapses, facilitation of per-vesicle release probability is confounded by depletion. To overcome this, we obtained traces of free Ca 2+ concentration in response to various action potential stimulus trains from a molecular MCell model of a hippocampal Schaffer collateral axon. Ca 2+ sensors were placed at varying distance from a voltage-dependent calcium channel (VDCC) cluster, and Ca 2+ was buffered by calbindin. Then, using the calcium traces to drive deterministic state vector modelsmore »of synaptotagmin 1 and 7 (Syt-1/7), which respectively mediate synchronous and asynchronous release in excitatory hippocampal synapses, we obtained high-resolution profiles of instantaneous release rate, to which we applied functional fits. Synchronous vesicle release occurred predominantly within half a micron of the source of spike-evoked Ca 2+ influx, while asynchronous release occurred more consistently at all distances. Both fast and slow mechanisms exhibited multi-exponential release rate curves, whose magnitudes decayed exponentially with distance from the Ca 2+ source. Profile parameters facilitate on different time scales according to a single, general facilitation function. These functional descriptions lay the groundwork for efficient mesoscale modelling of vesicular release dynamics.« less
    Free, publicly-accessible full text available May 9, 2023
  10. Free, publicly-accessible full text available May 25, 2023