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Lipopolysaccharide mouse models for Parkinson's disease research:a critical appraisal

Journal of Water Resource and Protection（水资源与保护） 2024年第1期

作者： isaac Hall Mohammad Hassan Rezaie Boroon

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Neural Regeneration Research 2022年第11期17卷 2413-2417页

作者： isaac Deng Larisa Bobrovskaya Health and Biomedical Innovation Clinical and Health SciencesUniversity of South AustraliaAdelaideAustralia

Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory *** is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease *** central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative *** this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse *** will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.

关键词： C57BL/6 mice intranasal models lipopolysaccharide models neuroinflammation Parkinson's disease stereotaxic models substantia nigra systemic models

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

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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

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

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 ven.es 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

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

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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领导者的数字化领导力

经理人 2024年第9期 62-65页

作者：艾萨克·萨科里克美国StarCIO

企业领导者学习转型领导力技能,没有任何捷径。课堂学习不足以帮助形成领导多元化、敏捷和创新的团队,以及推动转型管理和文化变革。领导者还将遇到诸多挑战,需要培训团队如何综合利用数据,依靠直觉和倾听他人意见来做出决策。当转型项... 详细信息

企业领导者学习转型领导力技能,没有任何捷径。课堂学习不足以帮助形成领导多元化、敏捷和创新的团队,以及推动转型管理和文化变革。领导者还将遇到诸多挑战,需要培训团队如何综合利用数据,依靠直觉和倾听他人意见来做出决策。当转型项目遇到反对者时,领导者还得想好如何向他们推销自己的愿景、安抚他们的恐惧,并赢得他们的支持。

关键词：企业领导者领导力课堂学习推动转型数字化多元化

Prevalence of Induced Abortion among Female Students in Selected Tertiary Learning Institutions in Gaborone City, Botswana

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Lie Symmetries of Quasihomogeneous Polynomial Planar Vector Fields and Certain Perturbations

International Journal of Clinical Medicine（临床医学国际期刊） 2024年第3期 155页

作者： Mabole Masweu isaac Ogweno Owaka Rosebella Kipkalom

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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