3,689 research outputs found

    Nucleic Acid-Loaded Lipid Nanoparticle Interactions with Model Endosomal Membranes

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    [Image: see text] Lipid nanoparticles (LNPs) are important delivery systems for RNA-based therapeutics, yet the mechanism of their interaction with endosomal membranes remains unclear. Here, the interactions of nucleic acid-loaded LNPs that contain an ionizable lipid with models of the early and late endosomal membranes are studied, for the first time, using different reflectometry techniques. Novel insight is provided with respect to the subphase pH, the stage of the endosome, and the nature of the nucleic acid cargo. It is found that the insertion of lipids from the LNPs into the model membrane is greatest at pH 6.5 and 5.5, whereas at higher pH, lipid insertion is suppressed with evidence instead for the binding of intact LNPs, demonstrating the importance of the pH in the fusion of LNPs undergoing the endosomal pathway. Furthermore, and independently of the pH, the effect of the early- versus late-stage endosomal models is minimal, suggesting that the increased fluidity and anionic nature of the late endosome has little effect on the extent of LNP interaction. Last, there is greater nucleic acid delivery from LNPs containing mRNA than Poly(A), indicating that the extent of interaction can be tuned according to the nature of the nucleic acid cargo. Such new information on the relative impact of factors influencing nucleic acid delivery by LNP interactions with endosomal membranes is important in the design and tuning of vehicles with improved nucleic acid delivery capacities

    Second-Harmonic Generation in Silicon Nitride Ring Resonators

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    The emerging field of silicon photonics seeks to unify the high bandwidth of optical communications with CMOS microelectronic circuits. Many components have been demonstrated for on-chip optical communications, including those that utilize the nonlinear optical properties of silicon[1, 2], silicon dioxide[3, 4] and silicon nitride[5, 6]. Processes such as second harmonic generation, which are enabled by the second-order susceptibility, have not been developed since the bulk χ(2)\chi^{(2)} vanishes in these centrosymmetric CMOS materials. Generating the lowest-order nonlinearity would open the window to a new array of CMOS-compatible optical devices capable of nonlinear functionalities not achievable with the?χ(3)\chi^{(3)} response such as electro-optic modulation, sum frequency up-conversion, and difference frequency generation. Here we demonstrate second harmonic (SH) generation in CMOS compatible integrated silicon nitride (Si3N4) waveguides. The χ(2)\chi^{(2)} response is induced in the centrosymmetric material by using the nanoscale structure to break the bulk symmetry. We use a high quality factor Q ring resonator cavity to enhance the efficiency of the nonlinear optical process and detect SH output with milliwatt input powers.Comment: 4 pages, 3 figure

    Automated recognition of malignancy mentions in biomedical literature

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    BACKGROUND: The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining. RESULTS: We developed a named entity recognizer (MTag), an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall) and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance. CONCLUSION: Together, these results suggest that the identification of disparate biomedical entity classes in free text may be achievable with high accuracy and only moderate additional effort for each new application domain

    The Extraordinary X-ray Light Curve of the Classical Nova V1494 Aquilae (1999 #2) in Outburst: The Discovery of Pulsations and a "Burst"

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    V1494 Aql (Nova Aql 1999 No. 2) was discovered on 2 December 1999. We obtained Chandra ACIS-I spectra on 15 April and 7 June 2000 which appear to show only emission lines. Our third observation, on 6 August, showed that its spectrum had evolved to that characteristic of a Super Soft X-ray Source. We then obtained Chandra LETG+HRC-S spectra on 28 September (8 ksec) and 1 October (17 ksec). We analyzed the X-ray light curve of our grating observations and found both a short time scale ``burst'' and oscillations. Neither of these phenomena have previously been seen in the light curve of a nova in outburst. The ``burst'' was a factor of 10 rise in X-ray counts near the middle of the second observation, and which lasted about 1000 sec; it exhibited at least two peaks, in addition to other structure. Our time series analysis of the combined 25 ksec observation shows a peak at 2500 s which is present in independent analyses of both the zeroth order image and the dispersed spectrum and is not present in similar analyses of grating data for HZ 43 and Sirius B. Further analyses of the V1494 Aql data find other periods present which implies that we are observing non-radial g+ modes from the pulsating, rekindled white dwarf.Comment: ApJ accepte

    Development and Characterization of Gallium-Doped Bioactive Glasses for Potential Bone Cancer Applications

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    In this study, we have developed a series of novel gallium oxide doped bioactive glasses to specifically target osteosarcoma cells while aiding new bone formation. The results show that osteosarcoma (Saos-2) cell death is induced through the addition of gallium oxide. Relative to the gallium-free control glass (0% Ga) glasses containing 1, 2, and 3% Ga decreased Saos-2 cell viability in a dose dependent manner. After 72 h in media preconditioned with 3% Ga Saos-2 cell viability was reduced by over 50%. Corresponding studies undertaken on primary normal human osteoblast cells (NHOst) demonstrated no adverse effects to the gallium containing glasses. Hydroxyapatite formation was observed for all glasses when exposed to simulated body fluid

    Methyl Oleate Synthesis by TiO2 Photocatalytic Esterification of Oleic Acid: Optimisation by Response Surface Quadratic Methodology, Reaction Kinetics and Thermodynamics

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    Methyl oleate, an example of a FAME (fatty acid methyl ester), was produced by oleic acid (OA) photoesterification with TiO2 and UVA light. Different parameters were evaluated and optimised: catalyst pretreatment, temperature (25–65°C), catalyst loading (1–30 % w/wOA) and oleic acid : alcohol molar ratio (1 : 3–1 : 55). Response surface quadratic methodology obtained by central composite rotational design (RSM-CCRD) was used to evaluate the main operational conditions of the photoesterification process. A high conversion of 98 % (±0.8) at 55 °C, 20 % TiO2 (w/wOA), and 1(OA) : 55(methanol) molar ratio was achieved. The photoesterification mechanism is furthermore proposed. The Langmuir-Hinshelwood kinetic model considered the forward and backward reaction as first-order fits with the best accuracy (R2 of 0.997). The thermodynamic results (ΔG338.15K=−20.75 kJ/mol, ΔH=13.75 kJ/mol, and ΔS=0.47 kJ/mol.K) indicate that the operating conditions are important, both to supply the energy requirement of the reaction, but also to increase the miscibility of the reactants

    Improved extraction of pine bark for wood adhesives

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    Pine bark tannins must be subjected to sulphonation to have an acceptable solubility in water for the preparation of wood adhesives. In this study, several extraction variables (sodium sulphite and urea concentrations in the extraction white liquor, extraction time, bark/liquor ratio and temperature) were assessed for their effect on extraction yield, and on the phenol, sulphur and ash content of extracts. Temperature had the highest positive effect on extraction yield and on the yield of total phenols in the extract. Sulphur content (i.e., the degree of sulphonation) was influenced mostly by sulphite concentration in white liquor, as was ash content
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