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- Chang, Lei, et al.
(författare)
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Environmental harshness and unpredictability, life history, and social and academic behavior of adolescents in nine countries.
- 2019
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 55:4, s. 890-903
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Tidskriftsartikel (refereegranskat)abstract
- Safety is essential for life. To survive, humans and other animals have developed sets of psychological and physiological adaptations known as life history (LH) tradeoff strategies in response to various safety constraints. Evolutionarily selected LH strategies in turn regulate development and behavior to optimize survival under prevailing safety conditions. The present study tested LH hypotheses concerning safety based on a 6-year longitudinal sample of 1,245 adolescents and their parents from 9 countries. The results revealed that, invariant across countries, environmental harshness, and unpredictability (lack of safety) was negatively associated with slow LH behavioral profile, measured 2 years later, and slow LH behavioral profile was negatively and positively associated with externalizing behavior and academic performance, respectively, as measured an additional 2 years later. These results support the evolutionary conception that human development responds to environmental safety cues through LH regulation of social and learning behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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| 2. |
- Saher, Osama
(författare)
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Pharmaceutical insights into improving oligonucleotide delivery and efficacy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The power of gene therapy lies in their capacity to target a disease on a genetic level. Nucleic acid containing therapeutics can be utilized to treat, diagnose or prevent a possible disease or condition. However, the successful delivery of such molecules constitutes a major limitation. The field of gene therapy is revolving around finding the ideal balance between efficacious and safe delivery of gene therapeutics and oligonucleotides (ONs). Different chemistries and delivery vectors were investigated for such purpose. In paper I, the synergism between low generation peptide dendrimers and lipids demonstrated high transfection efficiency of splice-switching ONs compared to peptide dendrimers alone. 20 peptide dendrimers/lipid mixtures were tested to deliver a splice-switching ON in a HeLa Luc/705 reporter cell line (a cervical cancer cell line). Under serum-free conditions optimal complexes displayed 30-fold higher correction levels compared to untreated cells. However, their activity was abolished under serum condition. Surprisingly, sucrose addition to the formulation completely restored complexes efficacy in the presence of serum. Optimal sucrose-containing formulation altered the biodistribution profile more towards the liver and less towards the kidneys following systemic delivery in mice. The in vitro and in vivo results obtained with sucrose addition demonstrated the potential positive effect of excipient addition on the formulation efficacy and biodistribution behavior. Paper II was based on our findings in paper I aiming to optimize the transfection efficacy under serum conditions. We screened different sugar and polymer excipients with the optimal peptide dendrimer and buffer from our previous study. Using this approach, splicing correction levels increased to 95-fold higher in a HeLa Luc/705 reporter cell line compared to untreated cells. We also noticed the enhancement effects of excipients in other reporter cell lines derived from osteosarcoma, hepatocyte-carcinoma and neuroblastoma cells. Cytotoxicity assays highlighted the safety of the formulations which encouraged us to check their biodistribution in mice. We noticed that biodistribution profiles of the ON were influenced by the type of formulations suggesting that excipients can preferentially direct ON therapeutics to certain organs. Despite the success of the approaches used in papers I and II, the presence of many components in the formulation can make them difficult to reproduce. We therefore synthesized another class of peptide dendrimers with lipophilic components (fatty acids or hydrophobic amino acids) conjugated to their core. In paper III, we screened different lipophilic dendrimers and evaluated the efficacy of the transfection of splice-switching ONs in reporter cell models. Factors as composition, stereochemistry, and formulation buffer were investigated. We noticed that 3rd generation peptide dendrimers were more efficient than 2nd generation peptide dendrimers. The effect of stereochemistry was more evident in 3rd generation peptide dendrimers favoring D-amino acid composed dendrimers. Variable results were obtained in different cell lines and levels of correction with the optimal formulation reached 93-fold over untreated in HeLa Luc/705 cells. Toxicity levels were minimal, yet Polyvinyl alcohol 18 (PVA18) addition increased the toxicity of the best candidates. The potential efficacy of the lipophilic peptide dendrimers is inspiring for future optimization and evaluation of different conjugates and /or cargos. Paper IV addressed the possibility to apply a new strategy in which ONs are targeting the DNA structure (anti-gene ONs). Such strategy was tested in a Huntington disease (HD) cell model. HD is a neurodegenerative disorder caused by CAG•CTG repeat expansion at exon 1 of Huntingtin gene (HTT) leading to formation of mutant HTT (mHTT) transcript and protein. The utilized anti-gene ONs were composed of Locked nucleic acids (LNA)/DNA mixmer and are complementary to the template strand of HTT. We were able to down-regulate HTT mRNA using various anti-gene ONs lengths, LNA content, and fatty acid modifications. We observed that high LNA content was necessary for activity. However, ON length and phosphorothioate (PS) content had minimal impact. Additionally, ON containing palmitoyl-modified LNA were superior to conventional LNA/DNA mixmers in serum starvation conditions. Finally, it was apparent that the number and positioning of palmitoyl-modified LNA nucleotides greatly affected activity. Overall, our screening highlighted optimal designs of anti-gene ONs targeting HTT DNA. Further investigation may include other chemistries and other classes of trinucleotide repeat (TNR) disorders.
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| 5. |
- Edman, Ludvig, 1967-, et al.
(författare)
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Influence of the anion on the kinetics and stability of a light-emitting electrochemical cell
- 2003
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Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 138:3, s. 441-446
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Tidskriftsartikel (refereegranskat)abstract
- The selection of the anion is shown to be crucial for the response time and the lifetime of light-emitting electrochemical cells (LECs) fabricated with [co-block phenyl-substituted poly(para phenylene vinylene)]-PEO-LiX (X = Tf, TFSI, Tf-TFSI). With a mixed-anion (X = Tf-TFSI) salt. the LEC turned on in less than 0.4 s at ΔU = 4.0 V, with X = TFS1 it turned on in a few seconds, while X = Tf produced devices with significantly larger response times with a strong dependence on the film thickness. We attribute this significant variation in the response to the morphology of the PEO-LiX phase at room temperature: PEO-LiTf is largely crystalline with a correspondingly limited ionic mobility: PEO-LiTf-TFSI is amorphous with a relatively high mobility; and heat-treated PEO-LiTFSI is typically partially amorphous. For lifetimes. we focused on 3.0 ≤ ΔU ≤ 4.0 V since this range coincided with a crossover in performance for the X = Tf devices. At ΔU = 3.0 V, these lasted the entire measurement cycle (=55 h) with constant efficiency and only a small decrease in light output. At ΔU ≥ 3.25 V. the same devices exhibited a limited lifetime with a linear dependence on the salt concentration and a decrease in the efficiency with time. For X = TFSI. Tf-TFSI short lifetimes and a decrease in efficiency with time were obtained independent of the applied voltage. Considering recently published data on electrochemical stability, we propose that an irreversible overreduction of the anion is a significant side reaction that limits the lifetime of LEC systems.
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| 6. |
- Edman, Ludvig, 1967-
(författare)
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Ion Association and Ion Solvation Effects at the Crystalline−Amorphous Phase Transition in PEO−LiTFSI
- 2000
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 104:31, s. 7254-7258
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Tidskriftsartikel (refereegranskat)abstract
- From band shape analyses of the strong 740 cm-1 Raman mode of the TFSI anion, we deduce that the crystalline state of the P(EO)nLiTFSI system contains a very small amount of ion pairs (approximate to 7%), most probably belonging to the minor amorphous phase, for the n greater than or equal to 6 range. For all-amorphous samples, we found a small amount of ion pairs for n greater than or equal to 8, but a significant amount (approximate to 24%) for n = 6. This increase in ion pair formation coincides with a decrease in the relative solvation of lithium cations by polymeric ether oxygens, as detected from a careful study of the 863 cm-1 polymer-cation "breathing mode". We therefore propose that the local ionic structure is preserved during the melting of n greater than or equal to 8 compositions, but that there is a changeover from a predominately ether oxygen lithium coordination to a combined ether oxygen and anionic coordination of the lithium cations for more concentrated samples upon melting.
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| 9. |
- Edman, Ludvig, et al.
(författare)
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On-demand photochemical stabilization of doping in light-emitting electrochemical cells
- 2011
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Ingår i: Electrochimica Acta. - : Elsevier. - 0013-4686 .- 1873-3859. ; 56:28, s. 10473-10478
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Tidskriftsartikel (refereegranskat)abstract
- A highly functional p-n junction doping structure can be realized within a light-emitting electrochemical cell under applied voltage via ion redistribution and electrochemical doping. This doping structure will however dissipate when the formation voltage is removed due to the mobility of the dopant counter-ions. A number of concepts aimed at a spatial immobilization of the ions and the related stabilization of the doping structure have been presented, but they all suffer from long and poorly controlled stabilization periods and/or unpractical operational conditions. Here, we ntroduce a markedly fast and easy-to-control stabilization procedure involving the inclusion of a UV-sensitive photo-initiator compound into a carefully tuned active material in an light-emitting electrochemical cell device, and demonstrate that it is possible to cross-link the ions and stabilize the p-n junction doping via a short UV exposure step executed at room temperature. 1.
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