122 research outputs found

    From Misfolded Recombinant Proteins in vitro to Pathological Agents in vivo

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    The pathogenesis of a disease involves a stochastic refolding of the etiologic protein into a misfolded infectious state known as prion. Recently, there has been renewed interest in the possibility that proteins causing neurodegeneration are all prions. The \u3b2-sheet rich pathological \u3b1-synuclein (\u3b1-syn) can cross from the neurons of transplanted patients into the grafted cells, and induce a change in the structure of \u3b1-syn in Parkinson\u2019s disease (PD) is an example. The convergence of studies showing the presence of prions in the pathogenesis of common neurodegenerative maladies has since been remarkable. Studies on synthetic prions showed that recombinant (rec) prion protein (PrP) is refolded into infectious conformations in vitro. This synthetic prion protein stimulates the conversion of cellular PrP into nascent pathological PrP and induces the accumulation of the isoform that causes neurodegeneration in vivo. Using defined biophysical and biochemical conditions in vitro, we developed methods for the pathological conversion of recPrP into PrPSc, and we established whether synthetic pathological agents of rec human \u3b1-syn amyloids can be infectious, as Legname et al. showed for the first time in production of mammalian synthetic prions. The pathological conversion process of both PrP and \u3b1-syn required only purified recombinant proteins and common chemicals. We generated putative infectious materials that possess different conformational structures. Moreover, we designed a novel build-in screening methodology for amyloid preparations to achieve putative infectious materials using amyloid-infected-cell culture assay. At fifth cell passage after single infection, prion amyloid fibrils from different preparations induced endogenous PrPC to convert into PrPSc in both non-infected mouse hypothalamic GT1 and mouse neuroblastoma N2a cell lines. Moreover, these variant synthetic proteinaceous infectious agents can replicate and be detected by protein misfolding cyclic amplification (PMCA). Through this methodology that was used to obtain synthetic mammalian prions, we also tested whether recombinant human \u3b1-syn amyloids can infect neuronal cell lines in vitro, and wild-type mice in vivo. A single exposure to amyloid fibrils of human \u3b1-syn was sufficient to induce aggregation of endogenous \u3b1-syn in human neuroblastoma SH-SY5Y cells, mouse hypothalamic GT1 cells and mouse brains. Interestingly, we found pathological phosphorylated \u3b1-syn in amyloid-infected cells and in neurons and neurites of mice. These results suggest that recombinant human \u3b1-syn amyloids can promote endogenous \u3b1-syn aggregation and pathological post-translational modification. Upon subsequent passages, mice inoculated with either human \u3b1-syn amyloid or diseased mouse brain homogenates showed marked neurological symptoms resembling those of PD, as well as neuropathological \u3b1-syn inclusions in neurons

    IncepSE: Leveraging InceptionTime's performance with Squeeze and Excitation mechanism in ECG analysis

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    Our study focuses on the potential for modifications of Inception-like architecture within the electrocardiogram (ECG) domain. To this end, we introduce IncepSE, a novel network characterized by strategic architectural incorporation that leverages the strengths of both InceptionTime and channel attention mechanisms. Furthermore, we propose a training setup that employs stabilization techniques that are aimed at tackling the formidable challenges of severe imbalance dataset PTB-XL and gradient corruption. By this means, we manage to set a new height for deep learning model in a supervised learning manner across the majority of tasks. Our model consistently surpasses InceptionTime by substantial margins compared to other state-of-the-arts in this domain, noticeably 0.013 AUROC score improvement in the "all" task, while also mitigating the inherent dataset fluctuations during training

    Scattering Mechanisms from Roughness-induced Fluctuations in Charge Distributions in ZnO Surface Quantum Wells

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    We present a theoretical study of roughness-related scatteringmechanisms for electrons in single heterostructures, especilaly in Gaussian-doped ZnO surface quantum wells. We show that besides the conventional scatterings there must existroughness-related mechanisms of charge origin, which stem from fluctuations the electron density and the donor density in the bulk ZnO. The strength of the two charge-origin scattering sources is found to be comparable with the one of the standard one from fluctuations in the barrier position. The effect of the dielectric discontinuity on the scattering mechanisms is discussed

    Chemical Components of Essential Oils From the Leaves of Seven Species Belonging to Rutaceae Family from Binh Chau-Phuoc Buu Nature Reserve, Vietnam

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    Several plant species of the Rutaceae family are medicinal plants, oil bearing and food crops. To provide more information for utilization of some species of this family in Binh Chau-Phuoc Buu Nature Reserve, we extracted essential oils from the leaves of seven species of the Rutaceae family: Acronychia pedunculata (L.) Miq., Atalantia citroides Pierre ex Guillaumin, Clausena excavata Burm.f., Glycosmis pentaphylla (Retz.) DC., Luvunga scandens (Roxb.) Buch.-Ham. ex Wight & Arn, Melicope pteleifolia (Champ. ex Benth.) T.G. Hartley, and Micromelum sp., via hydrodistillation, and identified their components using GC/MS analysis. A total of 60 compounds were identified from essential oils of seven species. The main components of the essential oils isolated from five species, including A. pedunculata, C. excavata, M. pteleifolia, G. pentaphylla, and Micromelum sp., were caryophyllene (57.63% and 55.41% in A. pedunculata and C. excavata, respectively), 1,9-decadiyne (32.59%, M. pteleifolia), ÎČ-ocimene (23.10%, G. pentaphylla), and 3-carene (58.03%, Micromelum sp.). Additionally, this study revealed the chemical composition of essential oils of L. scandens and A. citroides for the first time. The main constituent of A. citroides was 7-oxabicyclo[4.1.0] heptane, 3-oxiranyl- (53.91%) and that of L. scandens was caryophyllene (34.66%). These findings provide the basis for further application of these species in medicine

    Optimization of protein extraction from "Cam" rice bran by response surface methodology

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    "Cam" rice bran was considered a waste product from rice, which is rich in natural compounds and protein owing to its outstanding nutritional value. This study aimed to establish an optimization model for extracting protein from rice bran, with two responses: extraction yield (%) and protein content (%). The variable parameters included were pH (8.5-9.5), stirring time (3.5-4.5 h), and enzyme incubation temperature (85-95°C). The coefficient of determination for both models were above 0.95, indicating a high correlation between the actual and estimated values. The maximum extraction yield and protein content were achieved when the conditions were set at pH of 9.02, stirring time of 4.02 h, and extraction temperature of 90.6°C. Under these optimum conditions, the predicted protein extracted from rice bran was 43.03% (moisture <13.0%), with an extraction yield of 15.9%. The findings of this study suggested that this protocol can enhance the utilization of rice bran and might be employed on a large scale in the food industry to exploit the nutritional source

    Efficient and adaptive incentive selection for crowdsourcing contests

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    The success of crowdsourcing projects relies critically on motivating a crowd to contribute. One particularly effective method for incentivising participants to perform tasks is to run contests where participants compete against each other for rewards. However, there are numerous ways to implement such contests in specific projects, that vary in how performance is evaluated, how participants are rewarded, and the sizes of the prizes. Also, the best way to implement contests in a particular project is still an open challenge, as the effectiveness of each contest implementation (henceforth, incentive) is unknown in advance. Hence, in a crowdsourcing project, a practical approach to maximise the overall utility of the requester (which can be measured by the total number of completed tasks or the quality of the task submissions) is to choose a set of incentives suggested by previous studies from the literature or from the requester’s experience. Then, an effective mechanism can be applied to automatically select appropriate incentives from this set over different time intervals so as to maximise the cumulative utility within a given financial budget and a time limit. To this end, we present a novel approach to this incentive selection problem. Specifically, we formalise it as an online decision making problem, where each action corresponds to offering a specific incentive. After that, we detail and evaluate a novel algorithm, HAIS, to solve the incentive selection problem efficiently and adaptively. In theory, in the case that all the estimates in HAIS (except the estimates of the effectiveness of each incentive) are correct, we show that the algorithm achieves the regret bound o

    Ultimate pretreatment of lignocellulose in bioethanol production by combining both acidic and alkaline pretreatment

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    Alkaline pretreatment has been known as the most popular method to process lignocellulosic materials for bioethanol production due to its simplicity and high efficiency. However, the waste water of the process has a very high basicity, which requires neutralization with acids upon further disposal. In this study, rubber wood saw dust (Hevea brasiliensis) was employed as lignocellulosic material and its pretreatment was inspected with both diluted H2SO4 and NaOH in different combination ways. Hereby, acid was used not only for waste water neutralization but also to contribute to lignin removal. Analysis results showed that an aqueous solution of 2.0 - 2.5 wt.% H2SO4 can be used to treat the biomass followed by alkaline pretreatment. By this so-called combo-pretreatment technique, cellulose was well preserved without significant hydrolysis while the final pretreatment efficiency was up to 63.0%, compared to 48.2% of using only the alkaline solution and 13.7% of using only the acidic solution. Finally, alkaline waste water can be mixed to be neutralized with acidic waste water from the two previous steps. This innovated technique improved the pretreatment efficiency almost without increasing in chemical cost

    Development of blood transfusion external quality assessment program at national scale

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    Introduction: External quality assessment is a crucial component in ensuring the quality of blood transfusion testing laboratories. Objectives: To develop a procedure for generating external quality assessment items for blood transfusion testing to evaluate participants' performance. Methods: Experimental research was conducted at Quality Control Center for Medical laboratory- University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. Three items, including red blood cell, serum, and atypical antibody serum samples, were assessed for homogeneity and stability; 5 assessment areas, including ABO grouping, Rh grouping, compatible cross matches, Coombs test, and screening of atypical antibodies, were utilized to evaluate the performance of 38 participants in the 2020-2021 period. Results: Red blood cell and serum samples maintained quality for a specific period at controlled temperatures, while serum samples with atypical antibodies showed stability at different temperatures. The participants demonstrated high satisfactory performance in ABO grouping, Rh grouping, Coombs test, and screening for atypical antibodies. However, the most unsatisfactory performance was reported in crossmatching, with 15% of participants unsatisfactory results. Conclusion: The procedure of production of proficiency testing items has been successfully developed, and its application at the national level is suggested to improve the quality of blood transfusion laboratories

    Flexible interactive retrieval SysTem 3.0 for visual lifelog exploration at LSC 2022

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    Building a retrieval system with lifelogging data is more complicated than with ordinary data due to the redundancies, blurriness, massive amount of data, various sources of information accompanying lifelogging data, and especially the ad-hoc nature of queries. The Lifelog Search Challenge (LSC) is a benchmarking challenge that encourages researchers and developers to push the boundaries in lifelog retrieval. For LSC'22, we develop FIRST 3.0, a novel and flexible system that leverages expressive cross-domain embeddings to enhance the searching process. Our system aims to adaptively capture the semantics of an image at different levels of detail. We also propose to augment our system with an external search engine to help our system with initial visual examples for unfamiliar concepts. Finally, we organize image data in hierarchical clusters based on their visual similarity and location to assist users in data exploration. Experiments show that our system is both fast and effective in handling various retrieval scenarios

    Sexual dysfunction in men aged 40–60 years old in infertile couples

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    This study aimed to determine sexual dysfunction (SD) and erectile disorder (ED) prevalence and analyze risk factors in older men of infertile couples. The study was a cross-sectional descriptive study conducted on male partners in infertile couples who were aged between 40–60 years. The study took place at the Hue Center for Reproductive Endocrinology and Infertility, Hue University Hospital, Viet Nam from January 2022 to August 2023. All participants were examinated and were privately asked to answer the International Index of Erectile Function (IIEF)-15 questionaires vietnamese-language version to diagnose sexual dysfunction and erectile disorder. The study sample consisted of 81 qualified men. The prevalence of SD was 51.9% (N = 42), of which the rate of ED accounted for 46.9% (N = 38). Among the 42 cases of SD, 37 were mild cases (45.8%), 1 was moderate (1.2%) and 4 were severe (4.9%). In all five sexual domains, it was found that the severity of SD was associated with lower scores (p < 0.001). Cardiovascular disease (CVD) was associated with severity of SD (p = 0.044). The decrease in scores of sexual desire and satisfaction could significantly affect sperm vitality and DNA fragmentation index. Age, number of living children and economic income were statistically correlated to SD domains (p < 0.05). Sexual dysfunction is a comprehensive disorder that affects each of the four phases of the sexual response cycle in older infertile men. It is a common disorder that could affect semen quality, leading to total sexual dysfunction and erectile disorder. Factors such as age, term births history, number of living children, geography and economic income are demography-sociology risk factors. Additionally, CVD with vascular endothelial damage mechanism has a statistically significant relationship with the severity of sexual dysfunction
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