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101.
Joaquín Gomis-Fons Hubert Schwarz Liang Zhang Niklas Andersson Bernt Nilsson Andreas Castan Anita Solbrand Joanne Stevenson Véronique Chotteau 《Biotechnology progress》2020,36(4):e2995
A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained. 相似文献
102.
Lucy E. Ridding Adrian C. Newton Sally A. Keith Robin M. Walls Anita Diaz Richard F. Pywell James M. Bullock 《Ecography》2021,44(1):33-43
The extinction debt, delayed species extinctions following landscape degradation, is a widely discussed concept. But a consensus about the prevalence of extinctions debts is hindered by a multiplicity of methods and a lack of comparisons among habitats. We applied three contrasting species–area relationship methods to test for plant community extinction debts in three habitats which had different degradation histories over the last century: calcareous grassland, heathland and woodland. These methods differ in their data requirements, with the first two using information on past and current habitat area alongside current species richness, whilst the last method also requires data on past species richness. The most data‐intensive, and hence arguably most reliable method, identified extinction debts across all habitats for specialist species, whilst the other methods did not. All methods detected an extinction debt in calcareous grassland, which had undergone the most severe degradation. We conclude that some methods failed to detect an extinction debt, particularly in habitats that have undergone moderate degradation. Data on past species numbers are required for the most reliable method; as such data are rare, extinction debts may be under‐reported. 相似文献
103.
Amino Acids - Solid-phase synthesis of cyclic, branched or side-chain-modified peptides typically involves introduction of a residue carrying a temporary side-chain protecting group that undergoes... 相似文献
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106.
Jean Guillon Anita Cohen Clotilde Boudot Alessandra Valle Vittoria Milano Rabindra Nath Das 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):432-459
Abstract A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in?vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in?vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays. 相似文献
107.
Daniela Nicole Filoni Rossana Pesi Maria Giovanna Careddu Marcella Camici Simone Allegrini Anita Collavoli 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1155-1160
IMP preferring cytosolic 5 ′-nucleotidase II (cN-II) is a widespread enzyme whose amino acid sequence is highly conserved among vertebrates. Fluctuations of its activity have been reported in some pathological conditions and its mRNA levels have been proposed as a prognostic factor for poor outcome in patients with adult acute myeloid leukemia. As a member of the oxypurine cycle, cN-II is involved in the regulation of intracellular concentration of 5′-inosine monophosphate (IMP), 5′-guanosine monophosphate (GMP), and also 5-phosphoribose 1-pyrophosphate (PRPP) and is therefore involved in the regulation of purine and pyrimidine de novo and salvage synthesis. In addition, several studies demonstrated the involvement of cN-II in pro-drug metabolism. Notwithstanding some publications indicating that cN-II is essential for the survival of several cell types, its role in cell metabolism remains uncertain. To address this issue, we built two eucaryotic cellular models characterized by different cN-II expression levels: a constitutive cN-II knockdown in the astrocytoma cell line (ADF) by short hairpin RNA (shRNA) strategy and a cN-II expression in the diploid strain RS112 of Saccharomyces cerevisiae. Preliminary results suggest that cN-II is essential for cell viability, probably because it is directly involved in the regulation of nucleotide pools. These two experimental approaches could be very useful for the design of a personalized chemotherapy. 相似文献
108.
Charles A. Krauth Anita T. Shortnacy John K Montgomery John A. Secrist III 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):915-917
Abstract The antiviral activity of adenosine-N1-oxide (1) and a variety of substituted 1-(benzyloxy) adenosines (2) has been re-investigated and significant in vitro activity vs. Vaccinia virus has been shown. In vivo activity in mice has also been demonstrated. 相似文献
109.
Arylamines and nitroarenes are very important intermediates in the industrial manufacture of dyes, pesticides and plastics, and are significant environmental pollutants. The metabolic steps of N-oxidation and nitroreduction to yield N-hydroxyarylamines are crucial for the toxic properties of arylamines and nitroarenes. Nitroarenes are reduced by microorganisms in the gut or by nitroreductases and aldehyde dehydrogenase in hepatocytes to nitrosoarenes and N-hydroxyarylamines. N-Hydroxyarylamines can be further metabolized to N-sulphonyloxyarylamines, N-acetoxyarylamines or N-hydroxyarylamine N-glucuronide. These highly reactive intermediates are responsible for the genotoxic and cytotoxic effects of this class of compounds. N-Hydroxyarylamines can form adducts with DNA, tissue proteins, and the blood proteins albumin and haemoglobin in a dose-dependent manner. DNA and protein adducts have been used to biomonitor humans exposed to such compounds. All these steps are dependent on enzymes, which are present in polymorphic forms. This article reviews the metabolism of arylamines and nitroarenes and the biomonitoring studies performed in animals and humans exposed to these substances. 相似文献
110.