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Related Concept Videos

PD Controller: Design01:26

PD Controller: Design

630
In automotive engineering, car suspension systems often employ Proportional Derivative (PD) controllers to enhance performance. PD controllers are utilized to adjust the damping force in response to road conditions. A controller, acting as an amplifier with a constant gain, demonstrates proportional control, with output directly mirroring input.
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...
630
Time-Domain Interpretation of PD Control01:07

Time-Domain Interpretation of PD Control

383
Proportional-Derivative (PD) control is a widely used control method in various engineering systems to enhance stability and performance. In a system with only proportional control, common issues include high maximum overshoot and oscillation, observed in both the error signal and its rate of change. This behavior can be divided into three distinct phases: initial overshoot, subsequent undershoot, and gradual stabilization.
Consider the example of control of motor torque. Initially, a positive...
383
Frequency-Domain Interpretation of PD Control01:24

Frequency-Domain Interpretation of PD Control

356
Proportional-Derivative (PD) controllers are widely used in fan control systems to improve stability and performance. A fan control system can be effectively represented using a Bode plot to illustrate the impact of a PD controller through its transfer function. The Bode plot visually conveys how PD control modifies the fan's response across various frequencies, providing a frequency domain interpretation of the controller's behavior.
The proportional control gain, combined with the...
356
Predicting Products: SN1 vs. SN202:27

Predicting Products: SN1 vs. SN2

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Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
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Neuromuscular Junction And Blockade01:29

Neuromuscular Junction And Blockade

4.8K
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
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The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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Related Experiment Video

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Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade: A Systematic Review and

Steve Lu1, Julie E Stein1, David L Rimm2

  • 1Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, Maryland.

JAMA Oncology
|July 19, 2019
PubMed
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Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) shows superior accuracy in predicting anti-PD-1/PD-L1 therapy response compared to PD-L1 IHC, TMB, or GEP alone. Combining biomarkers may improve predictive performance, warranting further investigation.

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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
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Area of Science:

  • Oncology
  • Immunotherapy
  • Biomarker Discovery

Background:

  • Predicting response to anti-PD-1/PD-L1 therapies is crucial for effective cancer treatment.
  • Several biomarkers, including PD-L1 IHC, TMB, GEP, and mIHC/IF, are used to assess pretreatment tumor tissue.
  • The relative diagnostic performance of these predictive biomarkers remains to be fully established.

Purpose of the Study:

  • To systematically compare the diagnostic accuracy of PD-L1 IHC, TMB, GEP, and mIHC/IF assays.
  • To evaluate their effectiveness in predicting patient response to anti-PD-1/PD-L1 therapy.

Main Methods:

  • A comprehensive literature search of PubMed and major oncology conference abstracts (2013-2018) was performed.
  • Studies assessing PD-L1 IHC (FDA-approved indications), TMB, GEP, and mIHC/IF for predicting anti-PD-1/PD-L1 response were included.
  • Diagnostic performance was analyzed using sROC curves, AUC, sensitivity, specificity, PPV, NPV, and likelihood ratios.

Main Results:

  • Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) demonstrated a significantly higher AUC (0.79) compared to PD-L1 IHC (0.65), GEP (0.65), and TMB (0.69).
  • Combined biomarker strategies (e.g., PD-L1 IHC + TMB) approached the performance of mIHC/IF, with an AUC of 0.74.
  • mIHC/IF showed superior positive predictive value (0.63) and positive likelihood ratio (2.86) compared to other individual modalities.

Conclusions:

  • PD-L1 IHC, TMB, and GEP show comparable, moderate accuracy in predicting anti-PD-1/PD-L1 treatment response.
  • mIHC/IF and multimodality biomarker approaches offer improved predictive performance over single assays.
  • Further research with larger cohorts is needed to validate these findings and optimize predictive analyte combinations for diverse tumor types.