Cargo adaptors regulate stepping and force generation of mammalian dynein-dynactin.

Cytoplasmic dynein is an ATP-driven motor that transports intracellular cargos along microtubules. Dynein adopts an inactive conformation when not attached to a cargo, and motility is activated when dynein assembles with dynactin and a cargo adaptor. It was unclear how active dynein-dynactin complexes step along microtubules and transport cargos under tension. Using single-molecule imaging, we showed that dynein-dynactin advances by taking 8 to 32-nm steps toward the microtubule minus end with frequent sideways and backward steps. Multiple dyneins collectively bear a large amount of tension because the backward stepping rate of dynein is insensitive to load. Recruitment of two dyneins to dynactin increases the force generation and the likelihood of winning against kinesin in a tug-of-war but does not directly affect velocity. Instead, velocity is determined by cargo adaptors and tail-tail interactions between two closely packed dyneins. Our results show that cargo adaptors modulate dynein motility and force generation for a wide range of cellular functions

An efficient Gehan-type estimation for the accelerated failure time model with clustered and censored data

In medical studies, the collected covariates usually contain underlying outliers. For clustered /longitudinal data with censored observations, the traditional Gehan-type estimator is robust to outliers existing in response but sensitive to outliers in the covariate domain, and it also ignores the within-cluster correlations. To take account of within-cluster correlations, varying cluster sizes, and outliers in covariates, we propose weighted Gehan-type estimating functions for parameter estimation in the accelerated failure time model for clustered data. We provide the asymptotic properties of the resulting estimators and carry out simulation studies to evaluate the performance of the proposed method under a variety of realistic settings. The simulation results demonstrate that the proposed method is robust to the outliers existing in the covariate domain and lead to much more efficient estimators when a strong within-cluster correlation exists. Finally, the proposed method is applied to a medical dataset and more reliable and convincing results are hence obtained.Comment: ready for submissio

Facile synthesis of CdS nanocrystals using thioglycolic acid as a sulfur source and stabilizer in aqueous solution

A novel method has been developed for the synthesis of CdS nanocrystals (NCs) using thioglycolic acid (TGA) as a sulfur source and stabilizer with the presence of hydrogen peroxide in an aqueous medium. The products were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. The results indicate that the product was of zinc-blend crystal structure in a sphere-like shape. The room-temperature luminescence spectra revealed that the emission peak of CdS NCs prepared in relatively short refluxing times (10-120 min) could be tuned from 518 nm to 610 nm, and the photoluminescence quantum yield of the as-prepared CdS NCs could reach as high as 12.6%. In addition, the mechanism of the CdS nanocrystals formation was preliminarily discussed.KEY WORDS: Chemical synthesis, CdS, Nanostructures, Optical properties, Photoluminescence spectroscopy Bull. Chem. Soc. Ethiop. 2011, 25(3), 393-398

AviationGPT: A Large Language Model for the Aviation Domain

The advent of ChatGPT and GPT-4 has captivated the world with large language models (LLMs), demonstrating exceptional performance in question-answering, summarization, and content generation. The aviation industry is characterized by an abundance of complex, unstructured text data, replete with technical jargon and specialized terminology. Moreover, labeled data for model building are scarce in this domain, resulting in low usage of aviation text data. The emergence of LLMs presents an opportunity to transform this situation, but there is a lack of LLMs specifically designed for the aviation domain. To address this gap, we propose AviationGPT, which is built on open-source LLaMA-2 and Mistral architectures and continuously trained on a wealth of carefully curated aviation datasets. Experimental results reveal that AviationGPT offers users multiple advantages, including the versatility to tackle diverse natural language processing (NLP) problems (e.g., question-answering, summarization, document writing, information extraction, report querying, data cleaning, and interactive data exploration). It also provides accurate and contextually relevant responses within the aviation domain and significantly improves performance (e.g., over a 40% performance gain in tested cases). With AviationGPT, the aviation industry is better equipped to address more complex research problems and enhance the efficiency and safety of National Airspace System (NAS) operations

Understand Funding Liquidity and Market Liquidity in a Regime-switching Model

We investigate the time-varying relationship of funding liquidity (FL) and market liquidity (ML) in a Markov regime-switching model. By using a comprehensive U.S. TRACE dataset, we provide strong evidence that FL and corporate bond ML are interlinked, and their impact on each other is highly regime-dependent. We find that FL and ML exhibit a large-and-positive mutual impact when money market is tight and equity market is volatile. But in normal regimes, FL is found to have a negative impact on ML with a much smaller magnitude than those in stressed regimes. Furthermore, FL is more stable than ML with less regime changes. Our paper offers insight on the important mechanism by which central banks can improve ML through the funding market

Anticonvulsant and sedative effect of Fufang Changniu pills and probable mechanism of action in mice

Purpose: To investigate the anticonvulsant and sedative effects of Fufang Changniu Pills (FCP) and its probable mechanism of action in mice.Methods: The water decoction of FCP was prepared and the main constituents were determined by high performance liquid chromatography (HPLC). The anticonvulsant activities of FCP were evaluated by maximal electroshock (MES) and  pentylenetetrazole (PTZ)-induced seizures in mice. Pentobarbital sodium-induced sleeping time and locomotor activity measurements were performed to evaluate the sedative effects of FCP in mice. Finally, PTZ-induced chronic seizures were  established, and expressions of gamma-aminobutyric acid A receptor (GABA-A) and glutamic acid decarboxylase 65 (GAD65) in the brains of the mice were assayed by western blot in order to explore the probable mechanisms of action of the drug.Results: Gallic acid, liquiritin, cinnamyl alcohol, cinnamic acid and glycyrrhizic acid were detected in FCP decoction. FCP (50, 100 and 200 mg/kg) showed significant anticonvulsant and sedative effects on epileptic mice induced by MES (p < 0.05) and PTZ (p < 0.05). Moreover, pentobarbital sodium-induced sleeping time and  locomotor activity tests showed that FCP possesses sedative effect (p < 0.05). Western blot data indicate that FCP significantly up-regulated GABA-A and GAD 65 in the brains of chronic epileptic rats (p < 0.05).Conclusion: FCP has significant anticonvulsant and sedative effects, and the  mechanism of its action may be related to the up-regulation of GABA-A and GAD 65 in mice brain.Keywords: Epilepsy, Fufang Changniu pills, Anticonvulsant, Sedative effect,  Gamma-aminobutyric acid, Glutamate dehydrogenas

Metabolite Profile of Alzheimer’s Disease in the Frontal Cortex as Analyzed by HRMAS 1H NMR

Background: Investigation on neurochemical changes in the frontal cortex in individuals with Alzheimer’s disease (AD) and different Apolipoprotein E (APOE) genotypes, using ex vivo solid-state high-resolution NMR analysis, may lead to a better understanding of the neurochemistry associated with AD as well as new AD-specific metabolite biomarkers that might potentially improve the clinical diagnosis of AD.Methods: Intact tissue samples of the frontal cortex were obtained from 11 patients and 11 age-matched non-demented controls. Metabolite profiles in all samples were analyzed ex vivo, using solid-state high-resolution magic angle spinning (HRMAS) 600 MHz 1H nuclear magnetic resonance (NMR). A logistic regression analysis was used to rank metabolites based on their level of contribution in differentiating the AD patient tissues and the controls, and different AD-associated APOE genotypes (APOE ε4 vs. APOE ε3).Results: Tissue samples from the AD patients showed significantly lower NAA/Cr (p = 0.011), Ace/Cr (p = 0.027), GABA/Cr (p = 0.005), Asp/Cr (p < 0.0001), mI/Cr (p < 0.0001), and Tau/Cr (p = 0.021), and higher PCho/Cr (p < 0.0001), GPCho/Cr (p < 0.0001), and α&β-Glc/Cr (p < 0.0001) than the controls did. Specifically, a newly observed resonance at 3.71 ppm, referred to as α&β-Glc, was observed in 90.9% of the AD samples (10/11). Samples with APOE ε4 also exhibited higher PCho/Cr (p = 0.0002), GPCho/Cr (p = 0.0001), α&β-Glc/Cr (p < 0.0001), and lower Asp/Cr (p = 0.004) and GABA/Cr (p = 0.04) than the samples with APOE ε3 did. In the logistic regression analysis, PCho, GPCho, ASP, and α&β-Glc were found to be the most relevant metabolites for differentiating the AD patient tissues and the controls, and different APOE genotypes.Conclusion: HRMAS 1H NMR with high spectral resolution and sensitivity offers a powerful tool to gain quantitative information on AD associated neurochemical changes. There are important neurochemical differences in the frontal cortex between the AD patient tissues and the controls, and between those with different APOE genotypes. The resonance (α&β-Glc) found at 3.71 ppm in the AD patient tissues may be further investigated for its potential in the diagnosis and monitoring of AD