scholarly journals Single-Domain SARS-CoV-2 S1 and RBD Antibodies Isolated from Immunized Llama Effectively Bind Targets of the Wuhan, UK, and South African Strains in vitro

2021 ◽  
Author(s):  
Divora Yemane ◽  
Ivan Lu ◽  
Winson Tiahjono ◽  
Lauren Rubidoux ◽  
Abbas Hussain ◽  
...  
Keyword(s):  
South African ◽  
False Negative ◽  
Single Domain ◽  
Original Strain ◽  
Rapid Antigen Detection Test ◽  
The United Kingdom ◽  
The Us ◽  
Single Domain Antibodies ◽  
The Uk

AbstractThe spreading of SARS-CoV-2 variants has become a major challenge of the current fight against the pandemic. Of particular concerns are the strains that have arisen from the United Kingdom (UK) and South Africa. The UK variant spreads rapidly and is projected to overtake the original strain in the US as early as in March 2021, while the South African variant appears to evade some effects of the current vaccines. Potential false-negative diagnosis using currently available antigen kits that may not recognize these variants could cause another wave of community infection. Therefore, it is imperative that antibodies used in the detection kits are validated for binding against these variants. Here we report that the nanoantibodies (nAbs in our terminology, also referred to as VHH fragments, single domain antibodies, nanobodies™) that we have developed for rapid antigen detection test bind the receptor binding domain (RBD) of the S1 protein from the original COVID-SARS-2 virus as well as those from the UK and South African variants. This finding validates our antibodies used in our assay for the detection of these major variant strains.

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

Home and Away. The Enlistment of Australian, Canadian, New Zealand, and South African Men in Dominion Expeditionary Forces in the United Kingdom during the Great War

Itinerario ◽  
2014 ◽  
Vol 38 (3) ◽  
pp. 45-58
Author(s):  
John Connor
Keyword(s):  
United Kingdom ◽  
New Zealand ◽  
South African ◽  
British Empire ◽  
Australian Government ◽  
South Africans ◽  
The United Kingdom ◽  
Canadian Citizenship ◽  
The Uk ◽  
The Great War

On the outbreak of war, men from the Dominions were scattered across the British Empire. As each Dominion began recruiting their expeditionary forces at home, the issue arose whether these expatriates, especially those resident in the United Kingdom, should join the British Army or be able to enlist in their Dominion's force. Canada and New Zealand allowed recruiting for the CEF and NZEF in the UK. Many Anglophone White South Africans joined a “colonial” battalion of the Royal Fusiliers. The Australian Government refused to allow Australians in the UK to join the AIF, despite the repeated requests of the Australian expatriate community. This paper examines the questions of British and sub-Imperial Dominion identities as well as the practical policy considerations raised by this issue. It argues that there is some evidence of nascent Dominion nationalism—the Canadian High Commission in London issued what became known as “a Certificate of Canadian Citizenship” to expatriates— but that Dominion Governments generally based their decisions on this issue based on cost and domestic political considerations.

Antitrust Regulation of IT Giants` Activities: Main Trends of Foreign and Russian Legislation

2021 ◽  
Author(s):  
D.V. Shram ◽  
Keyword(s):  
House Of Representatives ◽  
Network Effects ◽  
The United States ◽  
The European Union ◽  
The United Kingdom ◽  
The Us ◽  
The Usa ◽  
Economic Concentration ◽  
The Uk ◽  
Antitrust Regulation

The article is devoted to the antimonopoly regulation of IT giants` activities. The author presents an overview of the main trends in foreign and Russian legislation in this area. The problems the antimonopoly regulation of digital markets faces are the following: the complexity of determining the criteria for the dominant position of economic entities in the digital economy and the criteria for assessing the economic concentration in the commodity digital markets; the identification and suppression of cartels; the relationship between competition law and intellectual property rights in the digital age. Some aspects of these problems are considered through the prism of the main trends in the antimonopoly policy in the United States, the European Union, the United Kingdom and Russia. The investigation findings of the USA House of Representatives Antitrust Subcommittee against Apple, Google, Amazon and Facebook are presented. The author justifies the need to separate them, which requires the adoption of appropriate amendments to the antimonopoly legislation. The article analyzes the draft law of the European Commission on the regulation of digital markets – Digital Markets Act, reveals the criteria for classifying IT companies as «gatekeepers», and notes the specific approaches to antimonopoly regulation in the UK and the US. The article describes the concepts «digital platform» and «network effects», presented in the «fifth antimonopoly package of amendments», developed in 2018 by the Federal Antimonopoly Service of the Russian Federation, and gives an overview of the comments of the Ministry of Economic Development regarding these concepts wording in the text of the draft law, which formed the basis for the negative conclusion of the regulator. It is concluded that in the context of the digital markets’ globalization, there is a need for the international legal nature antitrust norms formation, since regional legislation obviously cannot cope with the monopolistic activities of IT giants.

Stella Artois in South Africa: Cause Marketing and the Building of a Global Brand

2019 ◽  
pp. 1-8
Author(s):  
Julie Hennessy
Keyword(s):  
South Africa ◽  
South African ◽  
Consumer Perceptions ◽  
Export Market ◽  
International Expansion ◽  
Export Markets ◽  
Cause Marketing ◽  
Global Brand ◽  
The Us ◽  
The Uk

Stella Artois, an AB InBev brand, is the world's best-selling Belgian beer. In early 2017, Ricardo Tadeu, AB InBev Zone President for Africa, is planning the brand's entry into its next export market: South Africa. The case explores Stella's introduction strategies into three of its export markets—the UK (1976), the US (2000), and Mexico (2016)—examining the drivers of the brand's success as well as its failures. Students will analyze the brand's previous launches to determine what made it successful in some markets and not in others. They will apply these learnings to develop a strategy for the brand's introduction to the South African market. Beyond the central discussion of growth through international expansion, the case addresses issues of brand positioning for premium products, changing consumer perceptions, the use of cause marketing, category development and maturity, and competitive strategy.

Efficacy of antibiotic-impregnated shunt catheters in reducing shunt infection: data from the United Kingdom Shunt Registry

2009 ◽  
Vol 4 (4) ◽  
pp. 389-393 ◽  
Author(s):  
Hugh K. Richards ◽  
Helen M. Seeley ◽  
John D. Pickard
Keyword(s):  
United Kingdom ◽  
Shunt Infection ◽  
Matched Pair ◽  
Csf Shunt ◽  
Accurate Information ◽  
Chi Square ◽  
The United Kingdom ◽  
Chi Square Test ◽  
The Uk

Object In recent years CSF shunt catheters impregnated with rifampicin and clindamycin have been introduced to the United Kingdom (UK) market. These catheters have been shown to be effective in vitro against cultures of Staphylococcus epidermidis. The authors used data collected by the UK Shunt Registry to assess the efficacy of antibiotic-impregnated catheters (AICs) against shunt infection by using a matched-pair study design. Methods The UK Shunt Registry contains data on nearly 33,000 CSF shunt-related procedures. The authors identified 1139 procedures in which impregnated catheters had been used, and accurate information was known about diagnosis, number of revisions, sex, and age in these cases. The database was ordered chronologically and searched forward and backward for cases with these same characteristics but involving conventional catheters. Matches were found for 994 procedures. Results Among the 994 procedures in which AICs had been used, 30 shunts were subsequently revised because of shunt infection. Among the 994 controls, 47 were subsequently revised for infection (p = 0.048, chi-square test). Conclusions The UK Shunt Registry does not collect data on causative organisms, and the surgeon is relied on entirely for the diagnosis of infection. However, with the large number of matched pairs evaluated, the authors attempted to reduce bias to a minimum. Their data suggest that AICs have the potential to significantly reduce shunt infections.

scholarly journals Article Commentary: Mitochondrial Replacement Techniques: Genetic Relatedness, Gender Implications, and Justice

2017 ◽  
Vol 1 (4) ◽  
pp. 1-6 ◽  
Author(s):  
Tetsuya Ishii ◽  
César Palacios-González
Keyword(s):  
Genetic Relatedness ◽  
Genetic Diagnosis ◽  
The United Kingdom ◽  
The Us ◽  
Child Centered ◽  
And Gender ◽  
Relevant Regulation ◽  
The Uk ◽  
Transfer Procedures ◽  
Mitochondrial Replacement Techniques

In 2015 the United Kingdom (UK) became the first nation to legalize egg and zygotic nuclear transfer procedures using mitochondrial replacement techniques (MRTs) to prevent the maternal transmission of serious mitochondrial DNA diseases to offspring. These techniques are a form of human germline genetic modification and can happen intentionally if female embryos are selected during the MRT clinical process, either through sperm selection or preimplantation genetic diagnosis (PGD). In the same year, an MRT was performed by a United States (U.S.)-based physician team. This experiment involved a cross-border effort: the MRT procedure per se was carried out in the US, and the embryo transfer in Mexico. The authors examine the ethics of MRTs from the standpoint of genetic relatedness and gender implications, in places that lack adequate laws and regulation regarding assisted reproduction. Then, we briefly examine whether MRTs can be justified as a reproductive option in the US and Mexico, after reassessing their legalization in the UK. We contend that morally inadequate and ineffective regulations regarding egg donation, PGD, and germline genetic modifications jeopardize the ethical acceptability of the implementation of MRTs, suggesting that MRTs are currently difficult to justify in the US and Mexico. In addition to relevant regulation, the initiation and appropriate use of MRTs in a country require a child-centered follow-up policy and more evidence for its safety.

Market volatility endangers moves to replace LIBOR

2020 ◽  
Keyword(s):  
United States ◽  
Interest Rates ◽  
Banking Sector ◽  
Market Volatility ◽  
Content Type ◽  
Consumer Loans ◽  
The United Kingdom ◽  
Interest Rate Swaps ◽  
The Us ◽  
The Uk

Subject The transition away from LIBOR. Significance The London Interbank Offered Rate (LIBOR) has been relied upon worldwide since 1970 for setting interest rates on syndicated loans, corporate debt, consumer loans, interest rate swaps and other derivatives. Following the 'LIBOR scandal' of 2008, the UK Financial Conduct Authority took over the regulation and administration of the rate, and no manipulation has emerged since 2013. Nevertheless, the United Kingdom and United States are determined to replace LIBOR. Impacts COVID-19 could prompt the US Fed to increase its support to the repo market, exacerbating fears that SOFR is not market determined. The scale and duration of COVID-19-related economic disruptions loom over banking sector profitability. Banks will struggle to balance immediate priorities triggered by COVID-19, and the need to devote staff and funds to the LIBOR transition.

FORMAL INSTITUTIONAL CONTEXTS AS OWNERSHIP OF INTELLECTUAL PROPERTY RIGHTS AND THEIR IMPLICATIONS FOR THE ORGANIZATION OF COMMERCIALIZATION OF INNOVATIONS AT UNIVERSITIES — COMPARATIVE DATA FROM SWEDEN AND THE UNITED KINGDOM

2011 ◽  
Vol 15 (05) ◽  
pp. 1069-1092 ◽  
Author(s):  
PETER LINDELÖF
Keyword(s):  
Technology Transfer ◽  
Transfer System ◽  
Science Parks ◽  
The United Kingdom ◽  
The Us ◽  
Institutional Contexts ◽  
The Individual ◽  
Historical Developments ◽  
The Uk ◽  
Similar Legislation

This paper identifies differences in institutional contexts (legislation) between Sweden and the UK and their effects on technology transfer policies. It then proceeds to examine how such activities are organized by universities. Empirical evidence from surveys conducted with technology transfer managers at eight Swedish universities and eleven UK universities gathered in Sweden and the UK during 2004 is analyzed. It is argued that the historical developments of these systems depend on different institutional contexts, which influence the modes of organization. The UK technology transfer system is based on similar legislation to that of the US, with IPRs being granted to the universities. The Swedish system, however, grants IPRs to the individual researchers, though with some new features — such as science parks and incubators — suggesting a change towards greater agent (university) involvement in encouraging technology transfer. This change indicates a breakthrough for the "entrepreneurial university" in Sweden.

scholarly journals Comparison in intersectional discrimination

Legal Studies ◽  
2018 ◽  
Vol 38 (3) ◽  
pp. 379-395 ◽  
Author(s):  
Shreya Atrey
Keyword(s):  
Black Women ◽  
South African ◽  
White Women ◽  
Personal Characteristics ◽  
White Men ◽  
Test Cases ◽  
Flexible Approach ◽  
The Us ◽  
Strict Requirement ◽  
The Uk

AbstractThis article considers the use of comparison in establishing multi-ground claims of intersectional discrimination. Leading examples of test cases from the US and the UK exemplify the challenges in using comparison to establish discrimination against Black women, based on the grounds of both race and sex. These challenges include: the insistence on using a single mirror comparator (viz white men) or the difficulties in choosing multiple comparators from a range of options (viz white women, Asian women, Black men, white men etc); the missing rationale for the selection; and the unwieldiness in actually appreciating the nature of intersectional discrimination based on this exercise. To overcome these, Canadian courts have relaxed the strict requirement of necessarily resorting to comparison for proving discrimination and switched to the flexible approach. However, in practice, flexible approach appears as fastidious as strict comparison in its selection and use of comparators. Thus, neither of the two approaches has been too helpful in supporting intersectional claims. The article argues that instead, a useful way of proving intersectional discrimination is to follow the South African approach of making comparisons contextually: (i) between all relevant comparators, identified in reference to one, some, and all of the grounds or personal characteristics; and (ii) sifting through comparative evidence with the purpose of establishing similar and different patterns of group disadvantage which characterise the nature of intersectional discrimination. This approach brings both principle and purpose to employing comparison and can be especially useful in appreciating intersectional discrimination as based on multiple grounds.

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