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1.
Heliyon ; 10(17): e37117, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39296206

RESUMO

The increasing frequency of climate-related hazards poses a significant risk to supply chains and marine insurance companies, which are already grappling with complex and interdependent global operations. Through a survey, this research examines the perceptions of an international cohort of marine insurers regarding their organization's participation in the Supply Chain Risk Management (SCRM) framework for climate change. In addition, the influence of respondents' experience levels and the World Bank's country classifications by income level are investigated. A repeated measures analysis of variance (ANOVA) is conducted to examine the effect of the SCRM framework's steps on perception, revealing significant variations among the steps and identifying gaps for improvement. While experience levels do not significantly affect involvement in the SCRM framework, distinct patterns emerge within each experience group, highlighting nuanced risk management practices. Comparing perceptions across World Bank income level categories reveals that higher country income levels generally correlate with higher average perception scores, indicating a potential association with greater awareness and management of climate change risks. The research also highlights the need for comprehensive involvement in all steps of the SCRM framework. Addressing climate change and building resilient supply chains requires a multi-faceted approach that includes enhanced risk management practices, and to this end, the authors' present areas for future research.

2.
Gene Ther ; 25(6): 415-424, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30069004

RESUMO

Recombinant adeno-associated virus (rAAV) has become the vector of choice for the development of novel human gene therapies. High-yield manufacturing of high-quality vectors can be achieved using the baculovirus expression vector system. However, efficient production of rAAV in this insect cell-based system requires a genetic redesign of the viral protein 1 (VP1) operon. In this study, we generated a library of rationally designed rAAV serotype 5 variants with modulations in the translation-initiation region of VP1 and investigated the potency of the resulting vectors. We found that the initiation strength at the VP1 translational start had downstream effects on the VP2/VP3 ratio. Excessive incorporation of VP3 into a vector type decreased potency, even when the VP1/VP2 ratio was in balance. Finally, we successfully generated a potent rAAV vector based on serotype 5 with a balanced VP1/VP2/VP3 stoichiometry.


Assuntos
Terapia Genética , Vetores Genéticos/genética , Parvovirinae/genética , Proteínas Virais/genética , Baculoviridae/genética , Proteínas do Capsídeo/genética , Dependovirus , Vetores Genéticos/uso terapêutico , Humanos , Óperon/genética , Sorogrupo , Proteínas Virais/uso terapêutico
3.
Proc Natl Acad Sci U S A ; 108(19): 7775-80, 2011 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-21518907

RESUMO

Protein translocation in Escherichia coli is mediated by the translocase that in its minimal form consists of the protein-conducting channel SecYEG, and the motor protein, SecA. SecYEG forms a narrow pore in the membrane that allows passage of unfolded proteins only. Molecular dynamics simulations suggest that the maximal width of the central pore of SecYEG is limited to . To access the functional size of the SecYEG pore, the precursor of outer membrane protein A was modified with rigid spherical tetraarylmethane derivatives of different diameters at a unique cysteine residue. SecYEG allowed the unrestricted passage of the precursor of outer membrane protein A conjugates carrying tetraarylmethanes with diameters up to , whereas a sized molecule blocked the translocation pore. Translocation of the protein-organic molecule hybrids was strictly proton motive force-dependent and occurred at a single pore. With an average diameter of an unfolded polypeptide chain of , the pore accommodates structures of at least , which is vastly larger than the predicted maximal width of a single pore by molecular dynamics simulations.


Assuntos
Proteínas de Escherichia coli/química , Adenosina Trifosfatases/química , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Conformação Proteica , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Transporte Proteico , Força Próton-Motriz , Canais de Translocação SEC , Proteínas SecA
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