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Related Concept Videos

Orthogonal Trajectories01:26

Orthogonal Trajectories

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Orthogonal trajectories describe the geometric relationship between two families of curves that intersect each other at right angles. One illustrative case involves a family of parabolas that open sideways along the x-axis. These curves share a common shape but differ by a scaling parameter, resulting in a set of curves that all pass through the origin and widen at different rates.Determining Orthogonal TrajectoriesTo identify the orthogonal trajectories for these parabolas, the first step...
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Pulse01:16

Pulse

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When the heart pumps blood out, arterial elastic fibers play a crucial role in sustaining a high-pressure gradient. They expand to accommodate the received blood and then recoil - a process known as the pulse that can be either manually palpated or electronically quantified. Despite a reduction in its effect with increased distance from the heart, elements of the pulse's systolic and diastolic components persist, observable even at the arteriole level.
The pulse serves as a clinical...
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Pulse01:05

Pulse

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The pulse is one of the most fundamental physiological indicators of the body's cardiovascular health. It is the rhythmic expansion and contraction of the arterial walls in response to the pressure generated by the heart's pumping action.
Pulse Rate and its Significance
Pulse rate, often measured in beats per minute (bpm), reflects the heart rate (HR), which is influenced by numerous factors such as stress, physical activity, and hormonal changes. A normal resting adult pulse rate falls...
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NMR Spectrometers: Radiofrequency Pulses and Pulse Sequences01:17

NMR Spectrometers: Radiofrequency Pulses and Pulse Sequences

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A pulse is a short burst of radio waves distributed over a range of frequencies that simultaneously excites all the nuclei in the sample. Upon passing a radio frequency pulse along the x-axis, the nuclei absorb energy corresponding to their Larmor frequencies and achieve resonance. This shifts the net magnetization vector from the z-axis toward the transverse plane. This angle of rotation of the magnetization vector, or the flip angle, is proportional to the duration and intensity of the pulse.
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Pulse Oximetry01:24

Pulse Oximetry

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Pulse oximetry, or SpO2, is a non-invasive method for continuously monitoring arterial oxygen saturation (SaO2). This procedure involves attaching a probe or sensor to the patient's fingertip, forehead, earlobe, or nose bridge. The sensor works by detecting changes in oxygen saturation levels through light signals generated by the oximeter and reflected by the pulsing blood under the probe.
Purpose
Average SpO2 values are greater than 95%. If the readings fall below 90%, it indicates that...
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Regulation of Pulse01:20

Regulation of Pulse

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Pulse regulation involves physiological mechanisms that ensure adequate blood flow throughout the body. The heartbeat, regulated by the autonomic nervous system, is influenced by hormonal balance, physical activity, and emotional state.
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Orthogonal Protein Purification Facilitated by a Small Bispecific Affinity Tag
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Pulse Proteolysis: An Orthogonal Tool for Protein Formulation Screening.

Lavanya K Iyer1, Rahul Phanse1, Meng Xu1

  • 1Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey 08903.

Journal of Pharmaceutical Sciences
|September 27, 2018
PubMed
Summary
This summary is machine-generated.

Pulse proteolysis offers a reliable method to predict protein formulation stability. This technique accurately ranks formulations, unlike standard biophysical methods, by measuring proteolytic resistance.

Keywords:
electrophoresisenzyme(s)protein aggregationprotein formulationprotein structurestability

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Area of Science:

  • Biochemistry
  • Analytical Chemistry
  • Pharmaceutical Sciences

Background:

  • Predicting protein formulation stability is challenging, often requiring lengthy studies.
  • Developing rapid analytical methods for stability prediction is crucial for biopharmaceutical development.

Purpose of the Study:

  • To evaluate pulse proteolysis as a predictive analytical tool for protein solution-state stability.
  • To compare pulse proteolysis with standard biophysical techniques for assessing formulation stability.

Main Methods:

  • Four proteins were formulated with varying buffers and excipients.
  • Urea-induced unfolding followed by "pulse" proteolysis was performed.
  • Proteolytic resistance was quantified using capillary electrophoresis-sodium dodecyl sulfate (CE-SDS).
  • Orthogonal biophysical methods (DSF, DSC, DLS, CD, fluorescence) were employed.
  • Stability was monitored via size exclusion chromatography (SEC) under storage conditions.

Main Results:

  • Formulations with higher proteolytic resistance showed increased monomer content and thermal stability.
  • Pulse proteolysis demonstrated a strong correlation with SEC stability data.
  • Standard biophysical techniques showed poor correlation with SEC stability data.

Conclusions:

  • Pulse proteolysis is a quantitative and predictive tool for assessing protein conformational stability.
  • This method can reliably rank-order different protein formulations.
  • Pulse proteolysis provides an orthogonal approach to traditional stability assessment methods.