Newcastle Disease Virus (NDV) is an avian RNA virus, which was shown to be effective and safe for use in oncolytic viral therapy for several tumour malignancies. The presence of a multi basic ...cleavage site (MBCS) in the fusion protein improved its oncolytic efficacy in vitro and in vivo. However, NDV with a MBCS can be virulent in poultry. We aimed to develop an NDV with a MBCS but with reduced virulence for poultry while remaining effective in killing human tumour cells. To this end, the open reading frame of the V protein, an avian specific type I interferon antagonist, was disrupted by introducing multiple mutations. NDV with a mutated V gene was attenuated in avian cells and chicken and duck eggs. Although this virus still killed tumour cells, the efficacy was reduced compared to the virulent NDV. Introduction of various mutations in the fusion (F) and hemagglutinin-neuraminidase (HN) genes slightly improved this efficacy. Taken together, these data demonstrated that NDV with a MBCS but with abrogation of the V protein ORF and mutations in the F and HN genes can be safe for evaluation in oncolytic viral therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Newcastle Disease Virus (NDV) is an avian RNA virus, which was shown to be effective and safe for use in oncolytic viral therapy for several tumour malignancies. The presence of a multi basic ...cleavage site (MBCS) in the fusion protein improved its oncolytic efficacy in vitro and in vivo. However, NDV with a MBCS can be virulent in poultry. We aimed to develop an NDV with a MBCS but with reduced virulence for poultry while remaining effective in killing human tumour cells. To this end, the open reading frame of the V protein, an avian specific type I interferon antagonist, was disrupted by introducing multiple mutations. NDV with a mutated V gene was attenuated in avian cells and chicken and duck eggs. Although this virus still killed tumour cells, the efficacy was reduced compared to the virulent NDV. Introduction of various mutations in the fusion (F) and hemagglutinin-neuraminidase (HN) genes slightly improved this efficacy. Taken together, these data demonstrated that NDV with a MBCS but with abrogation of the V protein ORF and mutations in the F and HN genes can be safe for evaluation in oncolytic viral therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gender differences in academic careers Groeneveld, Sandra; Tijdens, Kea; van Kleef, Daphne
Equality, diversity and inclusion an international journal,
01/2012, Letnik:
31, Številka:
7
Journal Article
Recenzirano
Purpose
The purpose of this paper is to examine gender differences in promotion probabilities of the academic staff of a large university in The Netherlands, taking into account the sex segregated ...context of the faculty.
Design/methodology/approach
The study uses records of the university's personnel information system from 1990 to 2006, covering the data of 1,792 employees in the academic ranks who have entered since 1990. Cox regression models are used to test three hypotheses.
Findings
The findings show that women have lower promotion probabilities than men. The gender differences are primarily explained by differences in years of service and external mobility, and not by the sex segregated context of the faculty. A higher share of women decreases the odds of being promoted for both men and women. Gender differences in working hours do not explain the gender differences in promotion probabilities.
Originality/value
The paper adds to the existing literature because event history analyses have hardly been applied to personnel records for investigating the impact of the sex segregated context on promotion probabilities.
Gender differences in academic careers Groeneveld, Sandra; Tijdens, Kea; van Kleef, Daphne
Equality, Diversity and Inclusion: An International Journal,
10/2012, Letnik:
31, Številka:
7
Journal Article
Recenzirano
Purpose - The purpose of this paper is to examine gender differences in promotion probabilities of the academic staff of a large university in The Netherlands, taking into account the sex segregated ...context of the faculty.Design methodology approach - The study uses records of the university's personnel information system from 1990 to 2006, covering the data of 1,792 employees in the academic ranks who have entered since 1990. Cox regression models are used to test three hypotheses.Findings - The findings show that women have lower promotion probabilities than men. The gender differences are primarily explained by differences in years of service and external mobility, and not by the sex segregated context of the faculty. A higher share of women decreases the odds of being promoted for both men and women. Gender differences in working hours do not explain the gender differences in promotion probabilities.Originality value - The paper adds to the existing literature because event history analyses have hardly been applied to personnel records for investigating the impact of the sex segregated context on promotion probabilities.
An internship in another country has its perks Groeneveld, Margit; Verhoeven, Stefan; Westgeest, Daphne
Tijdschrift voor diergeneeskunde,
2008-Sep-15, Letnik:
133, Številka:
18
Magazine Article