A Local Accumulation Connected Spread Model of Neurofibrillary Tangle Propagation in the Human Neocortex

2021 ◽  
Author(s):  
Ian Andrew Kennedy
Keyword(s):  
Neurofibrillary Tangle ◽  
Human Neocortex ◽  
Spread Model ◽  
Local Accumulation

The Improvement of Paclitaxel Cytotoxicity using Nanocellulose based Nature Resources

2019 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
R Nahrowi ◽  
A Setiawan ◽  
Noviany Noviany ◽  
I Sukmana ◽  
S D Yuwono
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Natural Resources ◽  
Cell Viability ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Target Cell ◽  
Mitotic Cycle ◽  
Potential Sources ◽  
Local Accumulation

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose

scholarly journals Population collapse in Congo rainforest from 400 CE urges reassessment of the Bantu Expansion

2021 ◽  
Vol 7 (7) ◽  
pp. eabd8352
Author(s):  
Dirk Seidensticker ◽  
Wannes Hubau ◽  
Dirk Verschuren ◽  
Cesar Fortes-Lima ◽  
Pierre de Maret ◽  
...  
Keyword(s):  
Human Activity ◽  
Climatic Conditions ◽  
Radiocarbon Dates ◽  
Expansion Phase ◽  
Bantu Languages ◽  
Population Collapse ◽  
Early Stages ◽  
Linguistic Evidence ◽  
Spread Model ◽  
Migration Event

The present-day distribution of Bantu languages is commonly thought to reflect the early stages of the Bantu Expansion, the greatest migration event in African prehistory. Using 1149 radiocarbon dates linked to 115 pottery styles recovered from 726 sites throughout the Congo rainforest and adjacent areas, we show that this is not the case. Two periods of more intense human activity, each consisting of an expansion phase with widespread pottery styles and a regionalization phase with many more local pottery styles, are separated by a widespread population collapse between 400 and 600 CE followed by major resettlement centuries later. Coinciding with wetter climatic conditions, the collapse was possibly promoted by a prolonged epidemic. Comparison of our data with genetic and linguistic evidence further supports a spread-over-spread model for the dispersal of Bantu speakers and their languages.

scholarly journals Disruption of a RAC1-centred network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration

2020 ◽  
Vol 29 (5) ◽  
pp. 817-833 ◽  
Author(s):  
Masataka Kikuchi ◽  
Michiko Sekiya ◽  
Norikazu Hara ◽  
Akinori Miyashita ◽  
Ryozo Kuwano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Model ◽  
Neurofibrillary Tangle ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Protein Domain ◽  
Expression Data ◽  
Integrated Network ◽  
Age Dependent

Abstract The molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, including Rac1, as key players in PDN collapse. Using publicly available as well as our own gene expression data, we confirmed that the mRNA expression level of the RAC1 gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilized Drosophila as a genetic model and found that modest knockdown of Rac1 in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator of RAC1 in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were increased specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y caused RAC1 downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.

Quantifying parametric uncertainty in the Rothermel model

2008 ◽  
Vol 17 (5) ◽  
pp. 638 ◽  
Author(s):  
Edwin Jimenez ◽  
M. Yousuff Hussaini ◽  
Scott Goodrick
Keyword(s):  
Variance Reduction ◽  
Input Parameter ◽  
Parametric Uncertainty ◽  
Fire Spread ◽  
The United States ◽  
Linear System Of Equations ◽  
Spread Model ◽  
Non Linear System ◽  
The Impact ◽  
Sensitivity Derivative

The purpose of the present work is to quantify parametric uncertainty in the Rothermel wildland fire spread model (implemented in software such as BehavePlus3 and FARSITE), which is undoubtedly among the most widely used fire spread models in the United States. This model consists of a non-linear system of equations that relates environmental variables (input parameter groups) such as fuel type, fuel moisture, terrain, and wind to describe the fire environment. This model predicts important fire quantities (output parameters) such as the head rate of spread, spread direction, effective wind speed, and fireline intensity. The proposed method, which we call sensitivity derivative enhanced sampling, exploits sensitivity derivative information to accelerate the convergence of the classical Monte Carlo method. Coupled with traditional variance reduction procedures, it offers up to two orders of magnitude acceleration in convergence, which implies that two orders of magnitude fewer samples are required for a given level of accuracy. Thus, it provides an efficient method to quantify the impact of input uncertainties on the output parameters.

scholarly journals Reversing the catastrophe of neoliberal-led global capitalism in the time of coronavirus: Towards a democratic socialist alternative

2021 ◽  
pp. 030981682199711
Author(s):  
David Neilson
Keyword(s):  
Global Capitalism ◽  
Regulatory Architecture ◽  
Local Accumulation

This article first outlines key arguments that demonstrate how the ‘neoliberal model of development’s’ global unleashing of capital is leading human civilisation to the brink of collapse. This ‘intellectual pessimism’ informs the ‘optimistic will’ central to the second part of this article which outlines an alternative democratic socialist model of development. This alternative is founded on a project of global cooperation to construct a national-trans-national regulatory architecture that can facilitate an ecologically balanced, materially secure, flexible and democratically solidaristic collection of local accumulation regimes that in aggregate would comprise a sustainable, progressive and pandemic-preventing planetary mode of accumulation.

Diffusible amyloid oligomers trigger systemic amyloidosis in mice

2008 ◽  
Vol 415 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Sivanesan Senthilkumar ◽  
Edwin Chang ◽  
Rajadas Jayakumar
Keyword(s):  
Protein A ◽  
Mouse Tissue ◽  
Cytokine Induction ◽  
Amyloidogenic Proteins ◽  
Enhancing Factor ◽  
Amyloid Oligomers ◽  
Apparent Relationship ◽  
Amyloid Enhancing Factor ◽  
Local Accumulation

AA (amyloid protein A) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an intravenous injection of protein extracted from AA-laden mouse tissue. Previous findings affirm that AA fibrils can enhance the in vivo amyloidogenic process by a nucleation seeding mechanism. Accumulating evidence suggests that globular aggregates rather than fibrils are the toxic entities responsible for cell death. In the present study we report on structural and morphological features of AEF (amyloid-enhancing factor), a compound extracted and partially purified from amyloid-laden spleen. Surprisingly, the chief amyloidogenic material identified in the active AEF was diffusible globular oligomers. This partially purified active extract triggered amyloid deposition in vital organs when injected intravenously into mice. This implies that such a phenomenon could have been inflicted through the nucleation seeding potential of toxic oligomers in association with altered cytokine induction. In the present study we report an apparent relationship between altered cytokine expression and AA accumulation in systemically inflamed tissues. The prevalence of serum AA monomers and proteolytic oligomers in spleen AEF is consistent to suggest that extrahepatic serum AA processing might lead to local accumulation of amyloidogenic proteins at the serum AA production site.

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