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Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer＇s disease

Neural Regeneration Research 2018年第1期13卷 19-25页

作者： isaac G. Onyango Gertcia Biotechnology Charlottesville VA USA

Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

关键词： Alzheimer's disease mitochondria bioenergetics mitochondrial DNA neuroinflammation mitohormesis caloric restriction hypometabolism mitophagy mitochondrial biogenesis recombinant-human mitochondrial transcription factor A antioxidants proteasome mitochondrial transcription activator-like effector nucleases clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) caloric restriction stem cells

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Infection,Pain,and Itch

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Neuroscience Bulletin 2018年第1期34卷 109-119页

作者： isaac M.Chiu Department of Microbiology and Immunobiology Division of Immunology Harvard Medical School

Pain and itch are unpleasant sensations that often accompany infections caused by viral, bacterial, parasitic, and fungal pathogens. Recent studies show that sensory neurons are able to directly detect pathogens to mediate pain and itch. Nociceptor and pruriceptor neurons respond to pathogen-associated molecular patterns, including Toll-like receptor ligands, N-formyl peptides, and bacterial toxins. Other pathogens are able to silence neuronal activity to produce analgesia during infection. Pain and itch could lead to neuronal modulation of the immune system or behavioral avoidance of future patho- gen exposure. Conversely, pathogens could modulate neuronal signaling to potentiate their pathogenesis and facilitate their spread to other hosts. Defining how pathogens modulate pain and itch has critical implications for sensory neurobiology and our understanding of host- microbe interactions.

关键词： Pain Itch Bacteria Pathogens Infection Inflammation Viruses

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Geomechanical effects of stress shadow created by large-scale destress blasting

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Journal of Rock Mechanics and Geotechnical Engineering 2017年第6期9卷 1085-1093页

作者： isaac Vennes Hani Mitri Department of Mining and Materials Engineering McGill UniversityMontrealH3A 0E8Canada

This study aims to determine if large-scale choked panel destress blasting can provide sufficient beneficial stress reduction in highly-stressed remnant ore pillar that is planned for production. The orebody is divided into 20 stopes over 2 levels, and 2 panels are choke-blasted in the hanging wall to shield the ore pillar by creating a stress shadow around it. A linear-elastic model of the mining system is constructed with finite difference code FLAC3 D. The effect of destress blasting in the panels is simulated by applying a fragmentation factor(α) to the rock mass stiffness and a stress reduction factor(β) to the current state of stress in the region occupied by the destress panels. As an extreme case, the destress panel is also modeled as a void to obtain the maximum possible beneficial effects of destressing and stress *** stopes are mined in the stress shadow of the panels in 6 lifts and then backfilled. The effect of destress blasting on the remnant ore pillar is quantified based on stress change and brittle shear ratio(BSR) in the stress shadow zone compared to the base case without destress blasting. To establish realistic rock fragmentation and stress reduction factors, model results are compared to measured stress changes reported for case studies at Fraser and Brunswick mines. A 1.5 MPa immediate stress decrease was observed 20 m away from the panel at Fraser Mine, and a 4 MPa immediate stress decrease was observed 25 m away at Brunswick Mine. Comparable results are obtained from the current model with a rock fragmentation factor α of 0.2 and a stress reduction factor α of 0.8. It is shown that a destress blasting with these parameters reduces the major principal stress in the nearest stopes by 10-25 *** yields an immediate reduction of BSR, which is deemed sufficient to reduce volume of ore at risk in the pillar.

关键词： Destress blasting Preconditioning Rockbursts Strainbursts Numerical modeling Rock failure

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Combination of structural reliability and interval analysis

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Acta Mechanica Sinica 2008年第1期24卷 61-67页

作者： Zhiping Qiu Di Yang isaac Elishakoff Institute of Solid Mechanics Beihang University Beijing 100083 China Department of Mechanical Engineering Florida Atlantic UniversityBoca Raton FL 33431-0991 USA

In engineering applications, probabilistic reliability theory appears to be presently the most important method, however, in many cases precise probabilistic reliability theory cannot be considered as adequate and credible model of the real state of actual affairs. In this paper, we developed a hybrid of probabilistic and non-probabilistic reliability theory, which describes the structural uncertain parameters as interval variables when statistical data are found insufficient. By using the interval analysis, a new method for calculating the interval of the structural reliability as well as the reliability index is introduced in this paper, and the traditional probabilistic theory is incorporated with the interval analysis. Moreover, the new method preserves the useful part of the traditional probabilistic reliability theory, but removes the restriction of its strict requirement on data acquisition. Example is presented to demonstrate the feasibility and validity of the proposed theory.

关键词： Non-probabilistic Reliability Interval analysis Parameter estimation

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Supervised and Semi-supervised Methods for Abdominal Organ Segmentation: A Review

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International Journal of Automation and computing 2021年第6期18卷 887-914页

作者： isaac Baffour Senkyire Zhe Liu School of Computer Science and Communication Engineering Jiangsu UniversityZhenjiang 212013China Computer Science Department Ghana Communication Technology UniversityAccraGhana

Abdominal organ segmentation is the segregation of a single or multiple abdominal organ(s) into semantic image segments of pixels identified with homogeneous features such as color and texture, and intensity. The abdominal organ(s) condition is mostly connected with greater morbidity and mortality. Most patients often have asymptomatic abdominal conditions and symptoms, which are often recognized late;hence the abdomen has been the third most common cause of damage to the human body. That notwithstanding,there may be improved outcomes where the condition of an abdominal organ is detected earlier. Over the years, supervised and semi-supervised machine learning methods have been used to segment abdominal organ(s) in order to detect the organ(s) condition. The supervised methods perform well when the used training data represents the target data, but the methods require large manually annotated data and have adaptation problems. The semi-supervised methods are fast but record poor performance than the supervised if assumptions about the data fail to hold. Current state-of-the-art methods of supervised segmentation are largely based on deep learning techniques due to their good accuracy and success in real world applications. Though it requires a large amount of training data for automatic feature extraction, deep learning can hardly be used. As regards the semi-supervised methods of segmentation, self-training and graph-based techniques have attracted much research attention. Self-training can be used with any classifier but does not have a mechanism to rectify mistakes early. Graph-based techniques thrive on their convexity, scalability, and effectiveness in application but have an out-of-sample problem. In this review paper, a study has been carried out on supervised and semi-supervised methods of performing abdominal organ segmentation. An observation of the current approaches, connection and gaps are identified, and prospective future research opportunities are enu

关键词： Abdominal organ supervised segmentation semi-supervised segmentation evaluation metrics image segmentation machine learning

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Excellent strength-ductility combination of Cr_(26)Mn_(20)Fe_(20)Co20Ni_(14) high-entropy alloy at cryogenic temperatures

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Journal of Materials Science & Technology 2023年第23期154卷 166-177页

作者： Xuzhou Gao Wei Jiang Yiping Lu Zhigang Ding Jizi Liu Wei Liu Gang Sha Tongming Wang Tingju Li isaac T.H.Chang Yonghao Zhao Nano and Heterogeneous Materials Center School of Materials Science and Engineering Nanjing University of Science and Technology Nanjing 210094 China Key Laboratory of Solidification Control and Digital Preparation Technology (Liaoning Province) School of Materials Science and Engineering Dalian University of Technology Dalian 116024 China Herbert Gleiter Institute of Nanoscience Nanjing University of Science and Technology Nanjing 210094 China Metallurgy and Head of Liquid Metal Engineering (LiME) Doctoral Training Centre Brunel Centre for Advanced Solidification Technology (BCAST) Brunel University London Uxbridge UB8 3PH UK

In the present study,a face-centered cubic non-equiatomic Cr_(26)Mn_(20)Fe_(20)Co20Ni_(14) high-entropy alloy(HEA)with a low stacking fault energy of 17.6 mJ m^(−2) was prepared by vacuum induction melting,forging and annealing *** recrystallized sample is revealed to exhibit an excellent combination of strength and ductility over a wide temperature range of 4.2–293 *** decreasing temperature from 293 to 77 K,the ductility and ultimate tensile strength(UTS)gradually increase by 30% to 95% and 137% to 1020 MPa,*** the lowest temperature of 4.2 K,the ductility keeps 65% and the UTS increases by 200% to 1300 MPa,which exceed those published in the literature,including conventional 300 series stainless *** microstructural analyses of this alloy reveal a change of deformation mechanisms from dislocation slip and nano-twinning at 293 K to nano-phase transformation at 4.2 *** cooperation and competition of multiple nano-twinning and nano-phase transformation are responsible for the superior tensile properties at cryogenic *** study provides experimental evidence for potential cryogenic applications of HEAs.

关键词： High-entropy alloys Strength and ductility Cryogenic temperature Twinning Phase transformation

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Assessment of the impact of climate change on the occurrences of malaria,pneumonia,meningitis,and cholera in Lokoja City,Nigeria

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Regional Sustainability 2022年第4期3卷 309-318页

作者： isaac Ayo OLUWATIMILEHIN Joseph Omojesu AKERELE Tolulope Adedoyin OLADEJI Mojisola Hannah OMOGBEHIN Godwin ATAI Department of Geography Obafemi Awolowo UniversityIle Ife220101Nigeria Department of Geography Modibbo Adama University of TechnologyYola640001Nigeria Institute of Ecology and Environmental Studies Obafemi Awolowo UniversityIle Ife220101Nigeria

This study examined the impact of climate change on the occurrence of malaria,pneumonia,meningitis,and cholera in Lokoja City,Nigeria,with the aim of investigating the spatial distribution and prevalence of the four kinds of diseases as well as the coping strategies of people in the *** collected the rainfall and temperature data of Lokoja City during 2000-2020 from the National Aeronautics and Space Administration(NASA),and the medical records data of the four kinds of diseases from the Kogi State Ministry of *** also conducted a semi-structured questionnaire of 250 residents,who have experienced one of these diseases,to investigate their coping strategies with these *** Pearson correlation and multiple regression analysis were used to research the relationship between the climate parameters and cases of *** result showed annual variations in climatic parameters with R^(2)values of 0.0557,0.0009,and 0.4915 for rainfall,maximum temperature,and minimum temperature,respectively.A positive and significant relationship were observed between maximum temperature and malaria(r=0.80),rainfall and malaria(r=0.54),minimum temperature and meningitis(r=0.64),as well as rainfall and cholera(r=0.66)at P<0.05 *** the regression analysis R^(2)=0.71,0.50,and 0.52 for malaria,cholera,and meningitis,respectively at P<0.05 *** 2000-2020,cases of malaria were highest in Ward A with 15,422,while 715 cases of pneumonia were highest in Kupa North *** Ward A,3787 cases of cholera were recorded to be the highest,while cases of meningitis were highest in Kupa North Ward with 2383 *** revealed that malaria is more common in the wet season,while cholera and meningitis cases were highest in the dry *** study revealed that the most practiced coping strategy is the use of medications by about 90%of the *** studies are recommended in the study area to establish a causal link between climate change and disease occurre

关键词： Climate change Malaria Cholera Pneumonia Meningitis Occurrence of disease Coping strategy to disease

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Lie Symmetries of Quasihomogeneous Polynomial Planar Vector Fields and Certain Perturbations

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Acta Mathematica Sinica,English Series 2005年第1期21卷 185-192页

作者： Javier CHAVARRIGA isaac A.GARCIA Departament de Matemdtica Universitat de LleidaAvda.Jaume II6925001LleidaSpain

In this work we study Lie symmetries of planar quasihomogeneous polynomialvector fields from different points of view, showing its integrability. Additionally, we show thatcertain perturbations of such vector fields w... 详细信息

关键词： Lie symmetries Quasi-homogeneous systems Planar vector fields

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Performance Analysis of 112Gb/s×4-Channel WDM PDM-DQPSK Optical Label Switching System With Spectral Amplitude Code Labels

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Photonic Sensors 2017年第1期7卷 88-96页

作者： isaac Adjaye ABOAGYE Fushen CHEN Yongsheng CAO Key Laboratory of Optical Fiber Sensing and Communications Ministry of Education School of Communication andInformation Engineering University of Electronic Science and Technology of China Chengdu 611731 China

We present the performance analysis of ll2Gb/s-4 wavelength division multiplexing （WDM） 100GHz channel spacing polarization division multiplexed-differential quadrature phase shift keying （PDM-DQPSK） optical label switching system with frequency swept coherent detected spectral amplitude code labels. Direct detection is chosen to demodulate the payload by applying a polarization tracker, while 4-bits of 156Mb/s spectral amplitude code label is coherently detected with a scheme of frequently-swept coherent detection. We optimize the payload laser linewidth as well as the frequency spacing between the payload and label. The label and payload signal performances are assessed by the eye-diagram opening factor （EOF） and bit-error rate （BER） at 10 9 as a function of the received optical power （ROP） and the optical signal to noise ratio （OSNR）. The payload could well be demodulated after 900 km at a bit error rate of 10-3 using forward error correction （FEC）.

关键词： Optical label switching (OLS) polarization division multiplexed (PDM) spectral amplitude code(SAC) wavelength division multiplexing (WDM)

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SCADA Data-Based Support Vector Machine for False Alarm Identification for Wind Turbine Management

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Intelligent Automation & Soft Computing 2023年第9期37卷 2595-2608页

作者： Ana María Peco Chacón isaac Segovia Ramírez Fausto Pedro García Márquez Ingenium Research Group Universidad Castilla-La ManchaCiudad Real13071Spain

Maintenance operations have a critical influence on power gen-eration by wind turbines(WT).Advanced algorithms must analyze large volume of data from condition monitoring systems(CMS)to determine the actual working conditions and avoid false *** paper proposes different support vector machine(SVM)algorithms for the prediction and detection of false alarms.K-Fold cross-validation(CV)is applied to evaluate the classification reliability of these *** Control and Data Acquisition(SCADA)data from an operating WT are applied to test the proposed *** results from the quadratic SVM showed an accuracy rate of 98.6%.Misclassifications from the confusion matrix,alarm log and maintenance records are analyzed to obtain quantitative information and determine if it is a false *** classifier reduces the number of false alarms called misclassifications by 25%.These results demonstrate that the proposed approach presents high reliability and accuracy in false alarm identification.

关键词： Machine learning classification support vector machine false alarm wind turbine cross-validation

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