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| 2. |
- Hazlett, Karsten RO, et al.
(author)
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Adaptation of Francisella tularensis to the mammalian environment is governed by cues which can be mimicked in vitro
- 2008
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 76:10, s. 4479-4488
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Journal article (peer-reviewed)abstract
- The intracellular bacterium Francisella tularensis survives in mammals, arthropods, and freshwater amoeba. It was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted Francisella is unknown. As a foundation for our goal of identifying F. tularensis outer membrane proteins which are expressed during mammalian infection, we first sought to identify in vitro cultivation conditions that induce the bacterium's infection-derived phenotype. We compared Francisella LVS grown in brain heart infusion broth (BHI; a standard microbiological medium rarely used in Francisella research) to that grown in Mueller-Hinton broth (MHB; the most widely used F. tularensis medium, used here as a negative control) and macrophages (a natural host cell, used here as a positive control). BHI- and macrophage-grown F. tularensis cells showed similar expression of MglA-dependent and MglA-independent proteins; expression of the MglA-dependent proteins was repressed by the supraphysiological levels of free amino acids present in MHB. We observed that during macrophage infection, protein expression by intracellular bacteria differed from that by extracellular bacteria; BHI-grown bacteria mirrored the latter, while MHB-grown bacteria resembled neither. Naïve macrophages responding to BHI- and macrophage-grown bacteria produced markedly lower levels of proinflammatory mediators than those in cells exposed to MHB-grown bacteria. In contrast to MHB-grown bacteria, BHI-grown bacteria showed minimal delay during intracellular replication. Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of Francisella organisms that have emerged from macrophages.
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| 3. |
- Kong, Chang Sun, et al.
(author)
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Information-Theoretic Approach for the Discovery of Design Rules for Crystal Chemistry
- 2012
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In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 52:7, s. 1812-1820
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Journal article (peer-reviewed)abstract
- In this work, it is shown that for the first time that, using information-entropy-based methods, one can quantitatively explore the relative impact of a wide multidimensional array of electronic and chemical bonding parameters on the structural stability of intermetallic compounds. Using an inorganic AB(2) compound database as a template data platform, the evolution of design rules for crystal chemistry based on an information-theoretic partitioning classifier for a high-dimensional manifold of crystal chemistry descriptors is monitored. An application of this data-mining approach to establish chemical and structural design rules for crystal chemistry is demonstrated by showing that, when coupled with first-principles calculations, statistical inference methods can serve as a tool for significantly accelerating the prediction of unknown crystal structures.
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| 4. |
- Rai, Sanskriti, et al.
(author)
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Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson's disease: comparison with small extracellular vesicle miRNA
- 2023
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In: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 17
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Journal article (peer-reviewed)abstract
- Background: Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques.Methods: A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker.Results: In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change −1.04 to −7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was “upregulated” (p = 0.002) in plasma, whereas “downregulated” (p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls.Conclusion: We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.
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| 5. |
- Rajan, Krishna, et al.
(author)
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Dual-precision fixed-point arithmetic for low-power ray-triangle intersections
- 2020
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In: Computers and Graphics. - : Elsevier BV. - 0097-8493. ; 87, s. 72-79
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Journal article (peer-reviewed)abstract
- Ray-Triangle intersection is a fundamental computation in most ray tracing algorithms. The prohibitive cost of the ray-triangle test algorithms, however, limits the utilization of these algorithms in settings with low power budgets, such as mobile systems. In this work, we analyze the precision requirements for ray-triangle intersection and observe that for most of the rays a low-precision is sufficient and only for a small fraction of rays a high precision is required. Accordingly, we propose a dual-precision fixed-point hardware accelerator for ray-triangle intersection targeting low-power systems, where the higher resolution is only activated for tests deemed critical by our algorithm. Towards this goal, we develop a thresholding technique that autonomously switches between the lower and higher precisions, where the lower precision unit is used for the majority of the tests resulting in significant benefits in power consumption. We evaluate our methodology on a representative set of scenes and implement our proposed methodology in hardware. Our methodology introduces negligible accuracy in ray-triangle tests (less than 0.1%), while offering 86% power savings in consumption compared to a baseline floating-point design and 26% savings compared to a high-precision fixed-point design.
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| 6. |
- Rastogi, Simran, et al.
(author)
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Fluorescence-tagged salivary small extracellular vesicles as a nanotool in early diagnosis of Parkinson’s disease
- 2023
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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 21
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Journal article (peer-reviewed)abstract
- Background: Parkinson’s disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery.Methods: In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson’s disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography.Results: We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112).Conclusions: In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.
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| 7. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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