Partial adjustment toward target R&amp;D intensity

Chen, Yan

doi:10.1111/radm.12320

Cited by 11 publications

(9 citation statements)

References 65 publications

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“…We have shown earlier that a highly positive net charge and the presence of a fatty acid are important in complex formation between Transportan analogs and siRNA. 19 Several groups have used a stearic acid modification in histidine containing peptides, 16,25,26 but it has been shown that the length of the fatty acid chain plays a role in the transfection efficacy of nucleic acids by CPPs. 27 Therefore, in order to optimize the hydrophobicity with the fatty acid tail, and to test the optimal conditions for each peptide sequence, saturated fatty acid modifications of C18, C20 or C22 were tested.…”

Section: Design Of Ph-sensitive Histidine Containing Nickfect Peptidesmentioning

confidence: 99%

Enhancement of siRNA transfection by the optimization of fatty acid length and histidine content in the CPP

et al. 2019

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Extracellular synthetic nucleic acids, such as siRNAs, are unable to reach their intended targets efficiently.Therefore, delivery methods such as cell-penetrating peptides (CPP), which increase their transport, could enhance the potency of siRNA as therapeutic agents. The CPP NickFect55 (NF55) is an efficient peptide-based delivery vector, which has been previously used to deliver plasmid DNA into cells in vivo.To achieve higher intracellular delivery and bioactivity from the delivered cargo, we designed a series of histidine-containing peptides by optimizing pH-sensitivity, net charge, hydrophobicity, and charge distribution in the sequence of the CPP NF55. In the current work, we have applied a strategy where we have replaced amino acids in the C-terminus of the peptide in order to distribute hydrophobic and hydrophilic amino acids into distinct regions along the alpha-helical projection, including histidine amino acids into the sequence at the N-terminus, and optimizing the N-terminal fatty acid modification to suit the specific peptide sequence. We tested the CPPs based on the transfection efficacy, CPP/siRNA complex stability, and the properties of the CPPs, such as hemolytic activity, buffering capability and cell toxicity. As a result, we have introduced a new peptide with a completely redesigned N-terminus that displays adaptive response to its physical environment. This peptide -NickFect70 (NF70)efficiently condenses siRNA, protects the cargo against degradation and effectively mediates target gene knockdown both in mammalian cell culture and in vivo, in a mouse model. Fig. 4 Membrane activity of nickfect peptides. Hemolytic activity of peptides was measured after 1 h-incubation of murine red blood cells with peptide solutions at 37°C. After incubation released hemoglobin was quantified in the supernatant by measuring absorbance at 540 nm. (a) Cells in PBS pH 7.5 supplemented with 5% glucose at 37°C. as controls RBC in 2× PBS treated with 0.1% Triton X-100 with 5% glucose (100% hemolysis) and mQ with 5% glucose (0% hemolysis) were used. (b) Modeling of endosomolytic activity of CPPs using buffer solutions with different pH. Peptides were used at 0.75 µm concentrations. Hemolytic activity was assessed in PBS buffer at pH 5.5-7.5.

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Section: Design Of Ph-sensitive Histidine Containing Nickfect Peptidesmentioning

confidence: 99%

Enhancement of siRNA transfection by the optimization of fatty acid length and histidine content in the CPP

et al. 2019

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“…The lengths of gas bubbles and liquid slugs are mainly affected by the different bubble-forming mechanisms as discussed in detail by Ganapathy et al [86] and Fu et al [87]. Research agrees that the inlet design also significantly influences the generated lengths [87][88][89][90][91]. Scaling laws for often employed T-and Y-junctions and rarely applied other inlets such as showerheads and membranes may be found, e.g., in [92][93][94][95].…”

Section: Gas Bubble and Liquid Slug Lengthsmentioning

confidence: 89%

Hydrodynamics and Mass Transfer of Gas‐Liquid and Liquid‐Liquid Taylor Flow in Microchannels

2017

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Dedicated to Professor Rüdiger Lange on the occasion of his 65th birthday Hydrodynamics and mass transfer of both gas-liquid and liquid-liquid Taylor flow simulation in microchannels are reviewed. Theoretical approaches for description of hydrodynamic parameters and mass transfer characteristics are corroborated by comparison with available experimental results. Similarities and peculiarities of liquid-liquid flows versus gas-liquid Taylor flows in capillaries are discussed. Tools of mass transfer intensification of gas-liquid and liquid-liquid Taylor flow in microchannels are analyzed and optimal process conditions for gas-liquid Taylor flows are evaluated.

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“…They also find that these target leverage ratios typically vary a lot in different years and across different firms. Given that the partial adjustment model is a useful framework to analyse the dynamics of an interested variable with target setting, it has also been extended beyond the capital structure adjustment and applied in economic literature including governance structure (Wintoki et al 2012), risk taking (Calvet et al 2009) and R&D intensity (Chen 2018). Our work aims to shed light on studying the dynamics of the CO 2 intensity movement across time, and its relationship with the financial development factor by applying this useful tool in the climate change literature.…”

Section: Literature Reviewmentioning

confidence: 99%

Do countries adjust the carbon intensity of energy towards targets? The role of financial development on the adjustment

Hui¹,

Wong²

2021

SN Bus Econ

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A sign of emerging downward trends in the carbon intensity of energy (CO 2 intensity) is an early indicator of progress in transitioning to low-emission energy. To trade off the obligation of reducing carbon emissions against the cost saving benefits of using fossil fuels, a country may choose an optimal share of using lowemission energy. We apply the partial adjustment to investigate whether countries adjust their CO 2 intensities towards specific targets. Using the sample covering 62 economies from 1992 to 2013, we find that the gaps between their actual and target CO 2 intensities narrow over time, suggesting adjustment towards their optimal levels in the use of low-emission energy. Important determinants of countries' target CO 2 intensities include GDP growth, the share of fossil fuel consumption, shares of electricity production generated from fossil fuels versus non-fossil fuel sources, emission transfers related to trade activities, and emissions generated in cement production. Financial development is shown to have an asymmetrical moderating effect on the adjustment process towards targets among countries. Specifically, countries with a higher degree of financial development display faster downward than upward speeds of adjustment towards their targets. Indeed, countries with a higher degree of financial development consistently adjusted their CO 2 intensities faster downwards and slower upwards towards their targets, while countries with a lower degree of financial development adjusted their CO 2 intensities slower downwards and faster upwards. Such findings are not related to the state of economic development of the countries. This demonstrates that financial development plays an important role in mitigating CO 2 emissions, given that more developed and deeper financial markets could reallocate investment towards cleaner energy and thus increase the supply of low-emission energy.

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Partial adjustment toward target R&D intensity

Cited by 11 publications

References 65 publications

Enhancement of siRNA transfection by the optimization of fatty acid length and histidine content in the CPP

Enhancement of siRNA transfection by the optimization of fatty acid length and histidine content in the CPP

Hydrodynamics and Mass Transfer of Gas‐Liquid and Liquid‐Liquid Taylor Flow in Microchannels

Do countries adjust the carbon intensity of energy towards targets? The role of financial development on the adjustment

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