Systematic internal standard variability and issue resolution: two case studies

Bioanalysis ◽  
2019 ◽  
Vol 11 (18) ◽  
pp. 1685-1692 ◽  
Author(s):  
Tom Verhaeghe
Keyword(s):  
Stable Isotope ◽  
Case Studies ◽  
Internal Standard ◽  
Structural Analog ◽  
High Variability ◽  
Quality Controls ◽  
First Case ◽  
Standard Response

Two case studies are presented of validated assays where the internal standard showed high variability, and there was a clear response difference between study samples and standards and quality controls. In the first case a co-eluting peak boosted the stable isotope labeled internal standard response in samples from hepatically impaired subjects. In the second case the blank plasma matrix suppressed the structural analog internal standard response. For both assays the issue could be resolved by adapting the chromatographic conditions and re-validating the assay (case 1) or by diluting the study samples with blank plasma (case 2).

Inconsistent internal standard response in LC–MS/MS bioanalysis: an evaluation of case studies

Bioanalysis ◽  
2019 ◽  
Vol 11 (18) ◽  
pp. 1657-1667 ◽  
Author(s):  
Daniela Fraier ◽  
Luca Ferrari ◽  
Katja Heinig ◽  
Elke Zwanziger
Keyword(s):  
Case Studies ◽  
Method Development ◽  
Internal Standard ◽  
Reliability Of Results ◽  
Root Cause ◽  
Standard Response ◽  
Response Variation

Aim: Monitoring the internal standard (IS) response is common practice in bioanalysis by LC–MS/MS. IS response variation may raise questions on assay quality and should trigger investigations into the root cause. Results: In two case studies with IS variability, re-analysis of diluted samples and spiking predose study samples revealed no effect of IS variability on results. The D17-labeled IS in a third case proved not to be suitable during method development and was replaced by a differently labeled IS. Conclusion: Determining the exact root cause for varying IS response is not always feasible; however, assay accuracy and reliability of results should be demonstrated. In some cases, assay re-development is needed to solve the problem.

Interpreting Laser-Based Fault Localization Results: Case Studies

2019 ◽  
Author(s):  
Sukho Lee ◽  
John van den Biggelaar ◽  
Marc van Veenhuizen
Keyword(s):  
Case Studies ◽  
Circuit Design ◽  
High Sensitivity ◽  
Failure Behavior ◽  
Process Technology ◽  
Resistance Change ◽  
Voltage Imaging ◽  
Root Cause ◽  
First Case ◽  
Proper Interpretation

Abstract Laser-based dynamic analysis has become a very important tool for analyzing advanced process technology and complex circuit design. Thus, many good reference papers discuss high resolution, high sensitivity, and useful applications. However, proper interpretation of the measurement is important as well to understand the failure behavior and find the root cause. This paper demonstrates this importance by describing two insightful case studies with unique observations from laser voltage imaging/laser voltage probing (LVP), optical beam induced resistance change, and soft defect localization (SDL) analysis, which required an in-depth interpretation of the failure analysis (FA) results. The first case is a sawtooth LVP signal induced by a metal short. The second case, a mismatched result between an LVP and SDL analysis, is a good case of unusual LVP data induced by a very sensitive response to laser light. The two cases provide a good reference on how to properly explain FA results.

A Silicon Debugging Methodology on Customer Prototype for Wafer Foundries

2012 ◽  
Author(s):  
Mai Zhihong ◽  
Ng Tsu Hau ◽  
Dawood M. Khalid ◽  
Tan Pik Kee ◽  
Jeffrey Lam
Keyword(s):  
Case Studies ◽  
Semiconductor Industry ◽  
Full Information ◽  
Limited Information ◽  
Ip Protection ◽  
First Case ◽  
Silicon Debugging ◽  
Failure Location ◽  
Device Chip ◽  
Latch Up

Abstract IP protection is of major importance for a semiconductor company and only limited information is made available for device debugging for the product outsourced to a foundry. In order to position ourselves better in the ever competitive semiconductor industry, with the consideration of IP protection, we have to provide the customers with the Si debugging capability and device/chip verification services in foundry. This paper explores the Si debugging methodology and technique in a foundry. Two case studies are presented and discussed. The first case illustrates the isolation of the failure location by InGaAs microscopy, upon which the failure was identified to be caused by a latch-up issue. In the second case, due to confidentiality considerations from the customer, full information could not be provided to the foundry for silicon debugging. The paper illustrates the ability to effectively debug a failure despite being constrained by limited information from the customer.

Investigating the potential of redundant manipulators in narrow channels

2020 ◽  
pp. 095440622096451
Author(s):  
Ashish Singla ◽  
Jyotindra Narayan ◽  
Himanshu Arora
Keyword(s):  
Case Studies ◽  
Fuzzy Inference ◽  
Redundant Manipulators ◽  
Redundancy Resolution ◽  
Inference System ◽  
Narrow Channels ◽  
First Case ◽  
Task Priority ◽  
Patient Side

In this paper, an attempt has been made to investigate the potential of redundant manipulators, while tracking trajectories in narrow channels. The behavior of redundant manipulators is important in many challenging applications like under-water welding in narrow tanks, checking the blockage in sewerage pipes, performing a laparoscopy operation etc. To demonstrate this snake-like behavior, redundancy resolution scheme is utilized using two different approaches. The first approach is based on the concept of task priority, where a given task is split and prioritize into several subtasks like singularity avoidance, obstacle avoidance, torque minimization, and position preference over orientation etc. The second approach is based on Adaptive Neuro Fuzzy Inference System (ANFIS), where the training is provided through given datasets and the results are back-propagated using augmentation of neural networks with fuzzy logics. Three case studies are considered in this work to demonstrate the redundancy resolution of serial manipulators. The first case study of 3-link manipulator is attempted with both the approaches, where the objective is to track the desired trajectory while avoiding multiple obstacles. The second case study of 7-link manipulator, tracking trajectory in a narrow channel, is investigated using the concept of task priority. The realistic application of minimum-invasive surgery (MIS) based trajectory tracking is considered as the third case study, which is attempted using ANFIS approach. The 5-link spatial redundant manipulator, also known as a patient-side manipulator being developed at CSIR-CSIO, Chandigarh is used to track the desired surgical cuts. Through the three case studies, it is well demonstrated that both the approaches are giving satisfactory results.

scholarly journals Assessing Environmental Factors within the One Health Approach

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 240
Author(s):  
Sarah Humboldt-Dachroeden ◽  
Alberto Mantovani
Keyword(s):  
Case Studies ◽  
One Health ◽  
Animal Health ◽  
Grey Literature ◽  
Aflatoxin M1 ◽  
First Case ◽  
Italian Regions ◽  
Environmental Component ◽  
Environmental Considerations ◽  
The One

Background: One Health is a comprehensive and multisectoral approach to assess and examine the health of animals, humans and the environment. However, while the One Health approach gains increasing momentum, its practical application meets hindrances. This paper investigates the environmental pillar of the One Health approach, using two case studies to highlight the integration of environmental considerations. The first case study pertains to the Danish monitoring and surveillance programme for antimicrobial resistance, DANMAP. The second case illustrates the occurrence of aflatoxin M1 (AFM1) in milk in dairy-producing ruminants in Italian regions. Method: A scientific literature search was conducted in PubMed and Web of Science to locate articles informing the two cases. Grey literature was gathered to describe the cases as well as their contexts. Results: 19 articles and 10 reports were reviewed and informed the two cases. The cases show how the environmental component influences the apparent impacts for human and animal health. The DANMAP highlights the two approaches One Health and farm to fork. The literature provides information on the comprehensiveness of the DANMAP, but highlights some shortcomings in terms of environmental considerations. The AFM1 case, the milk metabolite of the carcinogenic mycotoxin aflatoxin B1, shows that dairy products are heavily impacted by changes of the climate as well as by economic drivers. Conclusions: The two cases show that environmental conditions directly influence the onset and diffusion of hazardous factors. Climate change, treatment of soils, water and standards in slaughterhouses as well as farms can have a great impact on the health of animals, humans and the environment. Hence, it is important to include environmental considerations, for example, via engaging environmental experts and sharing data. Further case studies will help to better define the roles of environment in One Health scenarios.

scholarly journals Linking a rapid throughput plate-assay with high-sensitivity stable-isotope label LCMS quantification permits the identification and characterisation of low β-L-ODAP grass pea lines

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Peter M. F. Emmrich ◽  
Martin Rejzek ◽  
Lionel Hill ◽  
Paul Brett ◽  
Anne Edwards ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Internal Standard ◽  
High Sensitivity ◽  
Spectrophotometric Assay ◽  
Rapid Screening ◽  
Grass Pea ◽  
Stable Isotope Label ◽  
Tissue Samples ◽  
Plate Assay ◽  
Accurate Quantification

Abstract Background Grass pea (Lathyrus sativus) is an underutilised crop with high tolerance to drought and flooding stress and potential for maintaining food and nutritional security in the face of climate change. The presence of the neurotoxin β-L-oxalyl-2,3-diaminopropionic acid (β-L-ODAP) in tissues of the plant has limited its adoption as a staple crop. To assist in the detection of material with very low neurotoxin toxin levels, we have developed two novel methods to assay ODAP. The first, a version of a widely used spectrophotometric assay, modified for increased throughput, permits rapid screening of large populations of germplasm for low toxin lines and the second is a novel, mass spectrometric procedure to detect very small quantities of ODAP for research purposes and characterisation of new varieties. Results A plate assay, based on an established spectrophotometric method enabling high-throughput ODAP measurements, is described. In addition, we describe a novel liquid chromatography mass spectrometry (LCMS)-based method for β-L-ODAP-quantification. This method utilises an internal standard (di-13C-labelled β-L-ODAP) allowing accurate quantification of β-L-ODAP in grass pea tissue samples. The synthesis of this standard is also described. The two methods are compared; the spectrophotometric assay lacked sensitivity and detected ODAP-like absorbance in chickpea and pea whereas the LCMS method did not detect any β-L-ODAP in these species. The LCMS method was also used to quantify β-L-ODAP accurately in different tissues of grass pea. Conclusions The plate-based spectrophotometric assay allows quantification of total ODAP in large numbers of samples, but its low sensitivity and inability to differentiate α- and β-L-ODAP limit its usefulness for accurate quantification in low-ODAP samples. Coupled to the use of a stable isotope internal standard with LCMS that allows accurate quantification of β-L-ODAP in grass pea samples with high sensitivity, these methods permit the identification and characterisation of grass pea lines with a very low ODAP content. The LCMS method is offered as a new ‘gold standard’ for β-L-ODAP quantification, especially for the validation of existing and novel low- and/or zero-β-L-ODAP genotypes.

scholarly journals Ocean Emission Effects on Aerosol-Cloud Interactions: Insights from Two Case Studies

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Armin Sorooshian ◽  
Hanh T. Duong
Keyword(s):  
Case Studies ◽  
Field Experiments ◽  
Remote Sensing Data ◽  
Anthropogenic Pollution ◽  
Cloud Microphysics ◽  
Marine Aerosols ◽  
Aerosol Cloud ◽  
First Case ◽  
Wide Range ◽  
Aerosol Cloud Interactions

Two case studies are discussed that evaluate the effect of ocean emissions on aerosol-cloud interactions. A review of the first case study from the eastern Pacific Ocean shows that simultaneous aircraft and space-borne observations are valuable in detecting links between ocean biota emissions and marine aerosols, but that the effect of the former on cloud microphysics is less clear owing to interference from background anthropogenic pollution and the difficulty with field experiments in obtaining a wide range of aerosol conditions to robustly quantify ocean effects on aerosol-cloud interactions. To address these limitations, a second case was investigated using remote sensing data over the less polluted Southern Ocean region. The results indicate that cloud drop size is reduced more for a fixed increase in aerosol particles during periods of higher ocean chlorophyll A. Potential biases in the results owing to statistical issues in the data analysis are discussed.

scholarly journals Systemic Design: Two Canadian Case Studies

2014 ◽  
Vol 7 (3) ◽  
Author(s):  
Alex Ryan ◽  
Mark Leung
Keyword(s):  
Resource Management ◽  
Case Studies ◽  
Systems Thinking ◽  
Management System ◽  
Design Thinking ◽  
Clean Energy ◽  
Resource Management System ◽  
First Case ◽  
Systemic Design

This paper introduces two novel applications of systemic design to facilitate a comparison of alternative methodologies that integrate systems thinking and design. In the first case study, systemic design helped the Procurement Department at the University of Toronto re-envision how public policy is implemented and how value is created in the broader university purchasing ecosystem. This resulted in an estimated $1.5 million in savings in the first year, and a rise in user retention rates from 40% to 99%. In the second case study, systemic design helped the clean energy and natural resources group within the Government of Alberta to design a more efficient and effective resource management system and shift the way that natural resource departments work together. This resulted in the formation of a standing systemic design team and contributed to the creation of an integrated resource management system. A comparative analysis of the two projects identifies a shared set of core principles for systemic design as well as areas of differentiation that reveal potential for learning across methodologies. Together, these case studies demonstrate the complementarity of systems thinking and design thinking, and show how they may be integrated to guide positive change within complex sociotechnical systems.

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