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Related Concept Videos

Derivatives of the Trigonometric Functions01:26

Derivatives of the Trigonometric Functions

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The motion of a Ferris wheel rotating at a constant speed provides an intuitive model for understanding trigonometric functions and their derivatives. As a rider moves along the circular path, the vertical height above the ground changes smoothly and periodically over time. This vertical motion can be accurately represented by a sine function, reflecting the repeating pattern of ascent and descent inherent to circular motion.Height and Rate of ChangeIf the rider’s height is modeled by a...
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Derivatives of Logarithmic Functions01:22

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Logarithmic and Exponential RelationshipA logarithmic function is the inverse of an exponential function. If y = logb x then, it can be rewritten as by = x. This relationship allows for implicit differentiation, making logarithmic functions useful in calculus. Logarithmic scales are widely used to represent data that span multiple orders of magnitude, such as earthquake magnitudes (Richter scale) and sound intensity (decibels).Differentiation of Logarithmic FunctionsTo differentiate y = logb x,...
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Second Derivatives of Implicit Functions01:29

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Elliptical arches are fundamental in architectural and structural engineering, offering aesthetic appeal and structural efficiency. The shape of an elliptical arch follows a constrained geometric relationship where the height and horizontal position are implicitly related. This means that the height y cannot be explicitly expressed as a function of the horizontal position x, necessitating implicit differentiation for slope and curvature analysis.The equation of an ellipse centered at the origin...
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Derivatives of Simple Functions01:27

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Derivatives quantify the rate of change of a function and can be interpreted geometrically as the slope of a straight line or the slope of a tangent line to a curve at a given point. In the context of a roller coaster, the derivative of the function describing the track’s horizontal position provides a mathematical description of how steep the path is at any location along the ride.Constant and Linear PathsA horizontal segment of a roller coaster can be modeled by a constant function,...
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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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When analyzing a beam subjected to various loads, it is crucial to understand the internal forces and moments generated within the structure. These internal forces can be broadly classified into normal forces, shear forces, and bending moments. To determine these forces and moments, we use the method of sections and apply a specific sign convention based on their direction and the side of the section being analyzed.
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Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with

Anders Lundin1, Louise Delsing2, Maryam Clausen3

  • 1Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal 43150, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.

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Human induced pluripotent stem cell-derived astroglia (NES-Astro) offer a novel model for studying astrocyte biology and neurological diseases, including apolipoprotein E (APOE) links.

Keywords:
apolipoproteins Eastrocytescalcium signalingcell differentiationdrug discoveryglutamate plasma membrane transport proteinshigh-throughput screening assaysinduced pluripotent stem cellsneurodegenerative diseasesneuroinflammation

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Cellular Biology

Background:

  • In vivo human brain studies face ethical and practical challenges.
  • Animal models have cellular differences, limiting their direct applicability.
  • Existing in vitro astrocyte models lack sufficient biological characterization.

Purpose of the Study:

  • To develop and characterize a novel human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) model.
  • To compare NES-Astro with other astrocytic models (primary, astrocytoma, hiPSC-derived).
  • To investigate the role of apolipoprotein E (APOE) in astrocyte biology.

Main Methods:

  • Generation of NES-Astro from long-term neuroepithelial-like stem (ltNES) cells.
  • Comprehensive characterization using transcriptomics and proteomics.
  • Functional assays including glutamate uptake, inflammatory response, and calcium signaling.
  • Assessment of APOE secretion and modulation by APOE-annotated compounds.

Main Results:

  • NES-Astro models were successfully developed and characterized.
  • Significant diversity was observed among different astrocytic models.
  • Cholesterol biosynthesis pathway modulation was confirmed in both adult and hiPSC-derived astrocytes.

Conclusions:

  • NES-Astro provides a biologically relevant model for studying human astrocytes.
  • Astrocytic model diversity necessitates careful consideration of cellular context in research.
  • This study highlights the importance of APOE in astrocyte function and disease.