scholarly journals Development of a Low-Molecular-Weight Aβ42 Detection System Using a Enzyme-Linked Peptide Assay

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1818
Author(s):  
Sang-Heon Kim ◽  
Eun-Hye Lee ◽  
Hyung-Ji Kim ◽  
A-Ru Kim ◽  
Ye-Eun Kim ◽  
...  

Alzheimer’s disease (AD) is a degenerative brain disease that is the most common cause of dementia. The incidence of AD is rapidly rising because of the aging of the world population. Because AD is presently incurable, early diagnosis is very important. The disease is characterized by pathological changes such as deposition of senile plaques and decreased concentration of the amyloid-beta 42 (Aβ42) peptide in the cerebrospinal fluid (CSF). The concentration of Aβ42 in the CSF is a well-studied AD biomarker. The specific peptide probe was screened through four rounds of biopanning, which included the phage display process. The screened peptide showed strong binding affinity in the micromolar range, and the enzyme-linked peptide assay was optimized using the peptide we developed. This diagnostic method showed specificity toward Aβ42 in the presence of other proteins. The peptide-binding site was also estimated using molecular docking analysis. Finally, the diagnostic method we developed could significantly distinguish patients who were classified based on amyloid PET images.

2021 ◽  
Author(s):  
Young Chul Youn ◽  
Jung-Min Pyun ◽  
Hye Ryoun Kim ◽  
Sungmin Kang ◽  
Nayoung Ryoo ◽  
...  

Abstract Background: The Multimer Detection System-Oligomeric amyloid-β (MDS-OAβ) level is a valuable blood-based biomarker for Alzheimer’s disease (AD). We used machine learning algorithms trained using multi-center datasets to examine whether blood MDS-OAβ values can predict AD-associated changes in the brain.Methods: A logistic regression model using TensorFlow (ver. 2.3.0) was applied to data obtained from 163 participants (amyloid positron emission tomography [PET]-positive and -negative findings in 102 and 61 participants, respectively). Algorithms with various combinations of features (MDS-OAβ levels, age, gender, and anticoagulant type) were tested 50 times on each dataset. Results: The predictive accuracy, sensitivity, and specificity values of blood MDS-OAβ levels for amyloid PET positivity were 78.16±4.97%, 83.87±9.40%, and 70.00±13.13%, respectively.Conclusions: The findings from this multi-center machine learning-based study suggest that MDS-OAβ values may be used to predict amyloid PET-positivity.


2008 ◽  
Vol 2008 (0) ◽  
pp. _OS0111-1_-_OS0111-2_
Author(s):  
Atsushi IWASAKI ◽  
Naoto MAKINO ◽  
Satoshi IZUMI ◽  
Shinsuke SAKAI ◽  
Junji SUGIMOTO ◽  
...  

Author(s):  
Muhammad Nouman Arif

Background: A new stain of corona virus COVID-19 got worldwide attention and has affected almost whole of the world population. Currently there is no specific vaccine or drug against COVID-19. Xu et al. (2020) built a homolog model of SARS-CoV-2 Mpro based on SARS-CoV Mpro which is considered as target to inhibit the replication of CoV. Objective: The aim of current study is to find potential inhibitors of COVID-19 Mpro using docking analysis. Methods: Autodockvina was used to carry out Protein-Ligand docking. COVID-19 main protease Mpro was docked with catechin and its different synthetic derivatives. Nelfinavir is an antiretroviral drug belongs to protease inhibitors was taken as standard. Results: According to the result obtained it was found that Compound (4) and Compound (1) have more affinity than nelfinavir. Conclusion: Compounds have a great potential to become COVID-19 main protease Mpro inhibitor. Nevertheless for their medicinal use further investigation is necessary.


2020 ◽  
Author(s):  
Jung-Min Pyun ◽  
Ji Sun Ryu ◽  
Ryan Lee ◽  
KyuHawn Shim ◽  
Young Chul Youn ◽  
...  

Abstract Background: Among other emerging amyloid-targeting blood-based biomarkers, Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) measures dynamic changes in concentration of oligomeric amyloid-β (OAβ), which is considered the main pathogenic culprit of Alzheimer’s disease (AD), in plasma after spiking with synthetic amyloid-β (Aβ). We aimed to investigate predictability of MDS-OAβ on amyloid Positron Emission Tomography (PET) positivity.Methods: A total of 96 subjects who visited Seoul National University Bundang Hospital for medical check-up complaining of cognitive decline and had undergone extensive medical assessment were recruited. Amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid PET. Plasma OAβ concentration was measured by MDS-OAβ. In the previous validation study, 0.78ng/ml was established as the cut-off value and the plasma OAβ concentration higher than or equal to the cut-off value was defined MDS-OAβ positive.Results: MDS-OAβ positivity could discriminate amyloid PET positivity with the AUC value of 0.855 (95% CI 0.776–0.933). Adding MDS-OAβ positivity to prediction models including age, MMSE score, and APOE ε4 status improved the performance up to the AUC value of 0.926 (95% CI 0.871–0.980).Conclusions: The Aβ oligomerization tendency in plasma could predict amyloid PET positivity with high performance, and when it is combined with age, MMSE score, and APOE ε4 status, the predictability was improved substantially. This suggests the potential of MDS-OAβ as a useful initial stage test in clinical and research field of AD.


With the increase in vehicle production and world population, more and more parking spaces and facilities are required. In this paper a new parking system called Smart Parking detection System is proposed to assist drivers in a residential building or office where all the owners or employee will be allotted with a particular parking space to know the occupancy of the parking space if any wrong car is parked in their slot. The new system uses infrared sensors to detect either car park occupancy or improper parking actions. Features of smart parking detection system include detection of car occupancy in a parking slot , getting information of the parked vehicle if it doesn’t matches with the car number registered and notify the details of the car parked by sending message to a registered phone number. This paper also describes the use of a metal rack to protect the sensors from external damage.


Author(s):  
J. B. Warren

Electron diffraction intensity profiles have been used extensively in studies of polycrystalline and amorphous thin films. In previous work, diffraction intensity profiles were quantitized either by mechanically scanning the photographic emulsion with a densitometer or by using deflection coils to scan the diffraction pattern over a stationary detector. Such methods tend to be slow, and the intensities must still be converted from analog to digital form for quantitative analysis. The Instrumentation Division at Brookhaven has designed and constructed a electron diffractometer, based on a silicon photodiode array, that overcomes these disadvantages. The instrument is compact (Fig. 1), can be used with any unmodified electron microscope, and acquires the data in a form immediately accessible by microcomputer.Major components include a RETICON 1024 element photodiode array for the de tector, an Analog Devices MAS-1202 analog digital converter and a Digital Equipment LSI 11/2 microcomputer. The photodiode array cannot detect high energy electrons without damage so an f/1.4 lens is used to focus the phosphor screen image of the diffraction pattern on to the photodiode array.


Author(s):  
P. Trebbia ◽  
P. Ballongue ◽  
C. Colliex

An effective use of electron energy loss spectroscopy for chemical characterization of selected areas in the electron microscope can only be achieved with the development of quantitative measurements capabilities.The experimental assembly, which is sketched in Fig.l, has therefore been carried out. It comprises four main elements.The analytical transmission electron microscope is a conventional microscope fitted with a Castaing and Henry dispersive unit (magnetic prism and electrostatic mirror). Recent modifications include the improvement of the vacuum in the specimen chamber (below 10-6 torr) and the adaptation of a new electrostatic mirror.The detection system, similar to the one described by Hermann et al (1), is located in a separate chamber below the fluorescent screen which visualizes the energy loss spectrum. Variable apertures select the electrons, which have lost an energy AE within an energy window smaller than 1 eV, in front of a surface barrier solid state detector RTC BPY 52 100 S.Q. The saw tooth signal delivered by a charge sensitive preamplifier (decay time of 5.10-5 S) is amplified, shaped into a gaussian profile through an active filter and counted by a single channel analyser.


Author(s):  
Huang Min ◽  
P.S. Flora ◽  
C.J. Harland ◽  
J.A. Venables

A cylindrical mirror analyser (CMA) has been built with a parallel recording detection system. It is being used for angular resolved electron spectroscopy (ARES) within a SEM. The CMA has been optimised for imaging applications; the inner cylinder contains a magnetically focused and scanned, 30kV, SEM electron-optical column. The CMA has a large inner radius (50.8mm) and a large collection solid angle (Ω > 1sterad). An energy resolution (ΔE/E) of 1-2% has been achieved. The design and performance of the combination SEM/CMA instrument has been described previously and the CMA and detector system has been used for low voltage electron spectroscopy. Here we discuss the use of the CMA for ARES and present some preliminary results.The CMA has been designed for an axis-to-ring focus and uses an annular type detector. This detector consists of a channel-plate/YAG/mirror assembly which is optically coupled to either a photomultiplier for spectroscopy or a TV camera for parallel detection.


Author(s):  
G.F. Bastin ◽  
H.J.M. Heijligers

Among the ultra-light elements B, C, N, and O nitrogen is the most difficult element to deal with in the electron probe microanalyzer. This is mainly caused by the severe absorption that N-Kα radiation suffers in carbon which is abundantly present in the detection system (lead-stearate crystal, carbonaceous counter window). As a result the peak-to-background ratios for N-Kα measured with a conventional lead-stearate crystal can attain values well below unity in many binary nitrides . An additional complication can be caused by the presence of interfering higher-order reflections from the metal partner in the nitride specimen; notorious examples are elements such as Zr and Nb. In nitrides containing these elements is is virtually impossible to carry out an accurate background subtraction which becomes increasingly important with lower and lower peak-to-background ratios. The use of a synthetic multilayer crystal such as W/Si (2d-spacing 59.8 Å) can bring significant improvements in terms of both higher peak count rates as well as a strong suppression of higher-order reflections.


Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.


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