4,773 research outputs found

    Probability-Based Liquefaction Evaluation Using Shear Wave Velocity Measurements

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    Three preliminary probability-based models and one artificial neural network model for evaluating soil liquefaction potential using shear wave velocity measurements are presented and compared with the deterministic curves developed by Andrus et al. The probability models are developed using logistic regression and Bayesian techniques applied to the same case history data used to develop the deterministic curves. The case history data consists of in situ shear wave velocity measurements at over 70 sites and field performance data from 26 earthquakes. The artificial neural network model is a high-order function capable of tracking the irregular boundary separating individual liquefaction and no liquefaction case histories. From the logistic regression and Bayesian models, the deterministic curve is characterized with a probability of about 30 %. This finding indicates that the shear wave-based deterministic curve and the SPT-based deterministic curve exhibit similar conservatism. The results provide a method for liquefaction risk analysis

    Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

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    Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

    Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

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    We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process

    Altered cortical thickness following prenatal sodium valproate exposure

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    Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA dose and right IFG thickness, and a close relationship between verbal skills and left IFG thickness. A significant interaction between group and hemispheric IFG thickness showed absence of the normal asymmetry in the IFG region of VPA-exposed children. These data provide preliminary insights into the putative neural basis of difficulties experienced by some VPA-exposed children

    A rapid, simple, and low-blank pumped ion-exchange column chromatography technique for boron purification from carbonate and seawater matrices

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    Funding: This work is supported by the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant 805246) to J.W.B.R., H.J., a Natural Environmental Research Council (NERC)-IAPETUS2 Doctoral Training Programme (DTP) Studentship to NE/S007431/1 C.X., a NERC-IAPETUS DTP Studentship NE/RO12253/1 to M.T., a Leverhulme Trust Early Career Fellowship ECF-2023-199 to H.J., a NERC UK IODP grant NE/P000878/1 to S.B. and S.N., and a Taiwanese MOST Grant 111-2116M-002-032-MY3 to S.N.Boron isotope ratios (Ī“11B) are used across the Earth Sciences and are increasing analyzed by Multi-Collector Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS). Accurate Ī“11B MC-ICPMS analysis requires boron purification from the sample matrix using ion-exchange column chromatography. However, the traditional gravity-drip column method is time-consuming and prone to airborne contamination due to its long duration and open resin surface. To address these issues, we designed a novel, simple, and reliable column chromatography technique called ā€œperi-columns.ā€ This method uses a peristaltic pump to generate vacuum on a commonly used column set up. This method uses sealed collection beakers and does not require solutions to pass through pump tubing, minimizing contamination. The duration is reduced by eight-fold, processing 12 samples in just 1.5Ā hr. It also yields low and consistent total procedural blanks, averaging 11Ā pg. The efficiency and efficacy of this method were tested by repeated boron purification from calcium carbonate and high-sodium matrices with international and in-house reference materials. The results matched those obtained using the gravity column method and fell within our laboratory long-term and international certified values. The mean Ī“11B and 2SD (standard deviation) of repeatedly processed NIST 8301f were 14.57Ā Ā±Ā 0.26ā€° (nĀ =Ā 31), NIST 8301c was 24.19Ā Ā±Ā 0.33ā€° (nĀ =Ā 10), STAiG-F1 was 16.20Ā Ā±Ā 0.26ā€° (nĀ =Ā 13), and seawater was 39.52Ā Ā±Ā 0.32ā€° (nĀ =Ā 10). All the components of our techniques are commercially available, and it is easily adaptable to other laboratories and isotope systems.Publisher PDFPeer reviewe

    From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

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    Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments

    Understanding the apparent fractional charge of protons in the aqueous electrochemical double layer

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    A detailed atomic-scale description of the electrochemical interface is essential to the understanding of electrochemical energy transformations. In this work, we investigate the charge of solvated protons at the Pt(111) | H_2O and Al(111) | H_2O interfaces. Using semi-local density-functional theory as well as hybrid functionals and embedded correlated wavefunction methods as higher-level benchmarks, we show that the effective charge of a solvated proton in the electrochemical double layer or outer Helmholtz plane at all levels of theory is fractional, when the solvated proton and solvent band edges are aligned correctly with the Fermi level of the metal (E_F). The observed fractional charge in the absence of frontier band misalignment arises from a significant overlap between the proton and the electron density from the metal surface, and results in an energetic difference between protons in bulk solution and those in the outer Helmholtz plane
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