scholarly journals Accelerated pharmaceutical protein development with integrated cell free expression, purification, and bioconjugation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Dominique Richardson ◽  
Jaakko Itkonen ◽  
Julia Nievas ◽  
Arto Urtti ◽  
Marco G. Casteleijn
2019 ◽  
Vol 16 (4) ◽  
pp. 307-313 ◽  
Author(s):  
Nasrin Zarkar ◽  
Mohammad Ali Nasiri Khalili ◽  
Fathollah Ahmadpour ◽  
Sirus Khodadadi ◽  
Mehdi Zeinoddini

Background: DAB389IL-2 (Denileukin diftitox) as an immunotoxin is a targeted pharmaceutical protein and is the first immunotoxin approved by FDA. It is used for the treatment of various kinds of cancer such as CTCL lymphoma, melanoma, and Leukemia but among all of these, treatment of CTCL has special importance. DAB389IL-2 consists of two distinct parts; the catalytic domain of Diphtheria Toxin (DT) that genetically fused to the whole IL-2. Deamidation is the most important reaction for chemical instability of proteins occurs during manufacture and storage. Deamidation of asparagine residues occurs at a higher rate than glutamine residues. The structure of proteins, temperature and pH are the most important factors that influence the rate of deamidation. Methods: Since there is not any information about deamidation of DAB389IL-2, we studied in silico deamidation by Molecular Dynamic (MD) simulations using GROMACS software. The 3D model of fusion protein DAB389IL-2 was used as a template for deamidation. Then, the stability of deamidated and native form of the drug was calculated. Results: The results of MD simulations were showed that the deamidated form of DAB389IL-2 is more unstable than the normal form. Also, deamidation was carried by incubating DAB389IL-2, 0.3 mg/ml in ammonium hydrogen carbonate for 24 h at 37o C in order to in vitro experiment. Conclusion: The results of in vitro experiment were confirmed outcomes of in silico study. In silico and in vitro experiments were demonstrated that DAB389IL-2 is unstable in deamidated form.


Author(s):  
Evan Osborne

Does humanity progress primarily through leaders organizing and directing followers, or through trial and error by individuals free to chart their own path? For most of human history ruling classes had the capacity and the desire to tightly regiment society, to the general detriment of progress. But beginning in the 1500s, Europeans developed a series of arguments for simply leaving well enough alone. First in the form of the scientific method, then in the form of free expression, and finally in the form of the continuously, spontaneously reordered free market, people began to accept that progress is hard, and requires that an immense number of mistakes be tolerated so that we may learn from them. This book tells the story of the development of these three ideas, and for the first time tells of the mutual influence among them. It outlines the rise, and dramatic triumph, of each of these self-regulating systems, followed by a surprising rise in skepticism, especially in the economic context. Such skepticism in the 20th century was frequently costly and sometimes catastrophic. Under the right conditions, which are more frequent than generally believed, self-regulating systems in which participants organize themselves are superior. We should accept their turbulence in exchange for the immense progress they generate.


2020 ◽  
Vol 37 (2) ◽  
pp. 153-169
Author(s):  
Teresa M. Bejan

AbstractThe classical liberal doctrine of free expression asserts the priority of speech as an extension of the freedom of thought. Yet its critics argue that freedom of expression, itself, demands the suppression of the so-called “silencing speech” of racists, sexists, and so on, as a threat to the equal expressive rights of others. This essay argues that the claim to free expression must be distinguished from claims to equal speech. The former asserts an equal right to express one’s thoughts without interference; the latter the right to address others, and to receive a hearing and consideration from them, in turn. I explore the theory of equal speech in light of the ancient Athenian practice of isegoria and argue that the equality demanded is not distributive but relational: an equal speaker’s voice should be counted as “on a par” with others. This ideal better captures critics’ concerns about silencing speech than do their appeals to free expression. Insofar as epistemic and status-harms provide grounds for the suppression and exclusion of some speech and speakers, the ideal of equal speech is more closely connected with the freedom of association than of thought. Noticing this draws attention to the continuing—and potentially problematic—importance of exclusion in constituting effective sites of equal speech today.


2021 ◽  
Author(s):  
Abhinav Dubey ◽  
Nikolay Stoyanov ◽  
Thibault Viennet ◽  
Sandeep Chhabra ◽  
Shantha Elter ◽  
...  

2020 ◽  
pp. 1-33
Author(s):  
Sandra Botero ◽  
Rachel Ellett ◽  
Thomas M. Keck ◽  
Stephan Stohler

Abstract The growth of judicial power globally has renewed scholarly debates about who benefits from increased judicial authority. Using original data, we examine the full universe of constitutional free expression decisions issued by three apex courts—in Colombia, India, and South Africa—across three categories of disputes that feature a diverse array of rights claimants. By so doing, we shed light on the limits of elite-driven accounts of judicial empowerment. We find that even where constitutional courts are empowered by elites seeking to advance their own interests, activist courts can develop a practice of rights-protection that benefits a diverse range of less powerful actors. Moreover, regardless of whether the speech claimants are elite or non-elite actors, these three apex courts regularly rule in favor of free expression for dissenting or unorthodox speech acts. In sum, where issues are peripheral to the governing regime’s core interests, relatively powerless actors are sometimes able to use legal processes to advance their rights and interests.


ChemBioChem ◽  
2016 ◽  
Vol 17 (10) ◽  
pp. 908-912 ◽  
Author(s):  
Mantas Liutkus ◽  
Samuel A. Fraser ◽  
Karine Caron ◽  
Dannon J. Stigers ◽  
Christopher J. Easton

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