Adventures in critical reagent lot changes in ligand-binding assays: redevelopment, bridging and additional processing requirements

Bioanalysis ◽  
2021 ◽  
Author(s):  
Alissa Rauwerdink ◽  
Michael Benson ◽  
Allison Jayne ◽  
Sathyapriya Babu ◽  
Jessica St Charles ◽  
...  

Aim: Critical reagents have significant impact on ligand-binding assay performance. The critical reagents selected during method development should be well-evaluated, as the quality of these reagents will dictate performance of the assay over time. Critical reagents in ligand-binding assays are almost always produced using a biological system, so batch yield, purity and performance tend to vary greatly. Due to the essential nature of critical reagents in the assay, changes in critical reagents can have dramatic impact on the assay and results, so close monitoring of assay performance is required. Methodology & results: We present here three examples of critical reagent lot changes that required creative solutions to maintain assay performance. The first case study is an example of the impact of different lots of analyte within a quantitative assay that resulted in the need to redevelop the assay in a different format. Case study two outlines an assay where a surrogate matrix is the critical reagent in an assay and the difficulties encountered over the course of several years and lot changes. The third case study covers an immunogenicity assay with a commercial detection that did not have sufficient quantity to cover the entire study lifecycle. As a result of the reagent change, a new assay was developed. Discussion & conclusion: A robust plan for critical reagent generation and lifecycle management should be adapted in order to avoid costly delays and rework. The performance of an assay depends on the continuity of the critical reagent supply. Reagents should be carefully selected to include the binding and performance properties required for an assay.

2021 ◽  
Vol 13 (14) ◽  
pp. 7600
Author(s):  
Wenting Ma ◽  
Rui Mu ◽  
Martin de Jong

Co-production is a solution by which the government provides public services. Co-production theory is built upon Western experience and currently focuses on the types of co-production in different policy stages, the barriers and governance strategies for co-production. However, little attention is paid to how political background will influence the co-production process. To fill the gap, we analyzed a case of co-production that occurred in China, and we characterized the political background as consisting of three main political features: political mobility, central–local relations, and performance measurement. Based on an in-depth case study of a government project in a medium-sized Chinese city, the impact and the changes of political features affecting governmental projects in different co-production stages are analyzed and assessed. We find that political features play a critical role in the co-production of China’s large government projects and may separately and jointly affect co-production. Government performance measurement affects the co-design and co-implementation of projects. Political mobility and changes in local government and performance measurement also affect the co-implementation continuity of the project. Political focus affects the co-design of projects. Central-local relations influence the support from higher government and the actual practices of lower government in the co-implementation stage.


1989 ◽  
Vol 2 (3) ◽  
pp. 204-212 ◽  
Author(s):  
Carol K. Jacobson

A Conceptual Framework for Evaluating Joint Venture Opportunities Between Hospitals and Physicians This paper reviews the changes in the competitive and regulatory environment and examines the impact of those changes on the relationships between hospitals and physicians. Transaction cost economics (TCE) provides a conceptual framework for examining the emergence of closer linkages between hospitals and physicians than the traditional independent hospital and medical staff organisations. TCE predicts that as investments in support of transactions become more specialised, closer linkages are more efficient. To illustrate, two case studies of successful hospital-physician joint ventures are presented. The first case study describes a joint venture between hospitals and physicians to purchase durable medical equipment. The second case describes the breakdown of an informal arrangement and the subsequent formation of a joint venture to organise a clinical programme. The discussion reports the rationale for choosing these structural arrangements and their key features, pointing out how TCE would account for the decision to establish a joint venture. The conclusion discusses the implications of this argument for the strategic decisions of health care managers.


2017 ◽  
pp. 869-893
Author(s):  
Ben Tran

Research suggests, according to Branch, Ramsay, and Barker (2013), that a significant number of people are exposed to persistent abusive treatment within the workplace, with the majority of studies within Europe indicating that between 10% and 15% of the workforce are exposed to workplace bullying (Zapf, Escartin, Einarsen, Hoel, & Vartia, 2011), with North American research reporting similar prevalence rates. This is a significant, ongoing dilemma for researchers and practitioners, for which an agreed resolution would be useful because of legal and policy implications. Hence, the purpose of this chapter is on the impact of organizational trauma on workplace behavior and performance based on workplace bullying. The chapter is based on a case study regarding a program that is funded by the Department of Education within a community college in the State of California. The community college is one of four community colleges under the same community college district.


2014 ◽  
Vol 2014 (DPC) ◽  
pp. 000545-000566
Author(s):  
John Hunt ◽  
Adren Hsieh ◽  
Eddie Tsai ◽  
Chienfan Chen ◽  
Tsaiying Wang

Nearly half a century ago the first die bumping was developed by IBM that would later enable what we call Wafer Level Packaging. It took nearly 40 years for Wafer Level Chip Scale Packaging (WLCSP), with all of the “packaging” done while still in wafer form to come into volume production. It began with very small packages having solderball counts of 2–6 I/Os. Over the years, the I/O count has grown, but much of the industry perception has remained that WLCSPs are limited to low I/O count, low power applications. But within the last few years, there have been growing demands for WLCSP packages to expand into applications with higher levels of complexity. With the ever increasing density and performance requirements for components in mobile electronic systems, the need has developed for an expansion of applicability for Wafer Level Package (WLP) technology. Wafer Level packaging has demonstrated a higher level of component density and functionality than has been traditionally available using standard packaging. This has led to the development of WLCSPs with larger die and increasing solderball connectivity counts. Development activity has been ongoing for improved materials and structures to achieve the required reliability performance for these larger die. For this study, we have evaluated several different metallic structures used for polymer core solderballs with two different WLCSP structures. The WLCSP structures which were evaluated included a standard 4-mask design with redistribution layer (RDL), using a Polymer 1, Metal RDL, Polymer2, and Under Bump Metallization (UBM); as well as a 3-mask design with RDL, using a Polymer 1, Metal RDL, and Polymer 2. In the first case, the solderballs are bonded to the UBM, while in the second case the balls are bonded to the RDL, using the Polymer 2 layer as the solder wettable defining layer. All of the combinations are tested using the standard JEDEC Temperature Cycling on Board (TCOB) and Drop Test (DT) methodologies. The two different metallurgies of the polymer core solderballs appear to react differently to the two different WLCSP structures. This suggests that the polymer core solderball compositions may perform best when optimized for the specific WLCSP structures that are manufactured. We will review the results of the impact of the different polymer core metallurgies on the TCOB and DT reliability performance of the WLCSPs, showing the interactions of these materials with the two WLCSP structures.


2013 ◽  
Vol 19 ◽  
pp. 157-174 ◽  
Author(s):  
Ellen D. Currano

Leaf-compression fossils with insect feeding traces are unique in providing rich, direct evidence of two levels in a fossil food web. Plant-insect associations dominate terrestrial trophic interactions, emphasizing the need to understand their ecological and evolutionary history. This paper first discusses methods of recognizing insect herbivore damage on fossil leaves and quantifying fossil insect herbivory. By conducting an unbiased insect damage census, damage frequency (percent of leaves with insect feeding damage), percent of leaf surface area removed by insects, and damage diversity (the number of discrete damage morphotypes, or DTs, found on a fossil flora or individual host plant) can all be measured. Three examples of responses of past plant-insect trophic interactions to environmental stresses are examined. In the first case study, late Oligocene fossil floras from Ethiopia document forest response to local perturbation and key characteristics to recognize disturbance in the plant fossil record. The second case study considers the terrestrial ecosystem response to the catastrophic global perturbation at the Cretaceous–Paleogene boundary. In the third case study, the impact of past global warming events—including the Paleocene–Eocene Thermal Maximum—on insect herbivory is discussed. Productive avenues for further research include: insect damage studies conducted outside the North American Cretaceous and Paleogene, actualistic and taphonomic studies of insect herbivory, and tighter collaboration across paleobotany, paleoentomology, botany, and entomology.


2019 ◽  
Vol 26 (5) ◽  
pp. 669-690
Author(s):  
Federico M Mucciarelli

This work addresses the impact of language diversity and nation-specific doctrinal structures on harmonized company law in the EU. With this aim, two emblematic case studies will be analysed. The first case study is related to the definition of ‘merger’ adopted in the Company Law Directive 2017/1132 (originally in the Third Company Law Directive and the Cross-Border Merger Directive); by relying on the example of the SEVIC case decided by the Court of Justice of the European Union (CJEU), it will be shown that scholars’ and courts’ conception of the definition of ‘merger’ varies according to own domestic doctrinal structures. The second case study is related to the notion of ‘registered office’, which is key for establishing the scope of several harmonizing provisions and the freedom of establishment; this paper analyses terminological fluctuations across language versions of EU legislation and the impact of domestic taxonomies and legal debates upon the interpretation of these notions. These case studies show that company law concepts, despite their highly technical nature, are influenced by discourse constructions conducted within national interpretative communities, and by the language used to draft statutory instruments and discuss legal issues. The task of the CJEU is to counterbalance these local tendencies, and yet it is unlikely that doctrinal structures, rooted in national languages and legal cultures, will disappear.


Author(s):  
Pablo Bellocq ◽  
Inaki Garmendia ◽  
Jordane Legrand ◽  
Vishal Sethi

Direct Drive Open Rotors (DDORs) have the potential to significantly reduce fuel consumption and emissions relative to conventional turbofans. However, this engine architecture presents many design and operational challenges both at engine and aircraft level. At preliminary design stages, a broad design space exploration is required to identify potential optimum design regions and to understand the main trade offs of this novel engine architecture. These assessments may also aid the development process when compromises need to be performed as a consequence of design, operational or regulatory constraints. Design space exploration assessments are done with 0-D or 1-D models for computational purposes. These simplified 0-D and 1-D models have to capture the impact of the independent variation of the main design and control variables of the engine. Historically, it appears that for preliminary design studies of DDORs, Counter Rotating Turbines (CRTs) have been modelled as conventional turbines and therefore it was not possible to assess the impact of the variation of the number of stages (Nb) of the CRT and rotational speed of the propellers. Additionally, no preliminary design methodology for CRTs was found in the public domain. Part I of this two-part publication proposes a 1-D preliminary design methodology for DDOR CRTs which allows an independent definition of both parts of the CRT. A method for calculating the off-design performance of a known CRT design is also described. In Part II, a 0-D design point efficiency calculation for CRTs is proposed and verified with the 1-D methods. The 1-D and 0-D CRT models were used in an engine control and design space exploration case study of a DDOR with a 4.26m diameter an 10% clipped propeller for a 160 PAX aircraft. For this application: • the design and performance of a 20 stage CRT rotating at 860 rpm (both drums) obtained with the 1-D methods is presented. • differently from geared open rotors, negligible cruise fuel savings can be achieved by an advanced propeller control. • for rotational speeds between 750 and 880 rpm (relatively low speeds for reduced noise), 22 and 20 stages CRTs are required. • engine weight can be kept constant for different design rotational speeds by using the minimum required Nb. • for any target engine weight, TOC and cruise SFC are reduced by reducing the rotational speeds and increasing Nb (also favourable for reducing CRP noise). However additional CRT stages increase engine drag, mechanical complexity and cost.


2013 ◽  
Vol 332 ◽  
pp. 218-223 ◽  
Author(s):  
Alina Ninett Panfir ◽  
Răzvan Boboc ◽  
Gheorghe Leonte Mogan

This paper proposes a new method of collaboration within a team of twoindividual NAO robots that should execute together a complex operation. The Naorobots are developed so as not only to act individually, but also to cooperatewith other robots if they cannot accomplish the operation alone. This paperpresents a case study demonstrating the integration of the humanoid roboticsplatform Nao within a cooperation application. This specific scenario ofinterest takes place in a small simulated manufacturing environment; while thetask being the storage of a big object, with different shape and weight. Thisscenario is used to observe the impact and performance that this particularteam of humanoid robots has in an industrial environment.Finally we present the successful implementation of robot – robot cooperationcapabilities inspired by human behaviour.


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