1,721,015 research outputs found
An amphipathic cell penetrating peptide aids cell penetration of cyclosporin A and increases its therapeutic effect in an in vivo mouse model for dry eye disease
No full textCell penetrating peptide (CPP), LK-3, causes a ca. 10-fold increase in the cell penetration of cyclosporin A (CsA) at nanomolar concentrations. The results of an in vivo dry eye mouse model demonstrated that a 100-fold lower dose of the CsA/LK-3 complex than that of Restasis (R) is sufficient to cause the same therapeutic effect.N
A dimeric alpha-helical cell penetrating peptide mounted with an HER2-selective affibody
No full textWe have developed a cell penetrating peptide (CPP) system with high selectivity and penetrability at nanomolar concentrations with a combination of an HER2-selective affibody, Z(HER2:342) (Z(HER2)), and a dimeric alpha-helical leucine- and lysine-rich peptide, LK-2. Z(HER2) and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-Z(HER2) protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-Z(HER2) has the ability to intracellularly deliver doxorubicin as a conjugate form to enhance its anti-cancer effect on HER2-overexpressing breast cancer cells with a great selectivity. The selective penetrability was confirmed in vitro, in 3D spheroids, and in in vivo models. LK-2-Z(HER2) has the capability to overcome the weak points of current CPPs, such as poor penetrability at low concentrations and a lack of selectivity, by combining powerful CPP and affibody sequences.N
One-bead-one-compound screening approach to the identification of cyclic peptoid inhibitors of cyclophilin D as neuroprotective agents from mitochondrial dysfunction
No full textIn an effort designed to discover superior inhibitors of cyclophilin D (CypD), we identified and screened members of a one-bead-one-compound (OBOC) library of cyclic peptoid analogues of cyclosporin A (CsA). The results show that the one member of this cyclic peptoid family, I11, inhibits mitochondrial membrane potential changes mediated by CypD.11Nsciescopu
Intracellular delivery of immunoglobulin G at nanomolar concentrations with domain Z-fused multimeric alpha-helical cell penetrating peptides
No full textA new vehicle is designed for the intracellular delivery of antibodies at nanomolar concentrations by combination of domain Z, a small affibody with strong binding affinity to Fc regions of immunoglobulin G (IgG), and the multimers of LK sequences, alpha-helical cell penetrating peptides (CPP) with powerful cell penetrating activities. Domain Z and multimeric LK are fused together to form LK-domain Z proteins. The LK-domain Z can bind with IgG at a specific ratio at nanomolar concentrations by simple mixing. The IgG/LK-domain Z complexes can successfully penetrate live cells at nanomolar concentration and the delivery efficiency is strongly dependent upon the concentrations of IgG/LK-domain Z complex as well as the species and subclasses of IgGs. The IgG/LK-domain Z complexes penetrate cells via ATP-dependent endocytosis pathway and the majority of delivered IgG seems to escape endosome to cytosol. Remarkably, the delivered IgGs are able to control the targeted intracellular signaling pathway as shown in the down-regulation of pro-survival genes by the delivery of anti-NF-kappa B using an LK-domain Z vehicle with a cathepsin B-cleavable linker between the LK sequence and domain Z. The simple but very efficient intracellular delivery method of antibodies at nanomolar concentrations is expected to facilitate profound understanding of cell mechanisms and development of new future therapeutics on the basis of intracellular antibodies.N
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Enhancing the sensitivity to seesaw mechanism predictions in gauged <math display="inline"><mi>B</mi><mo>-</mo><mi>L</mi></math> scenarios
Get PDFNew gauge bosons coupled to heavy neutral leptons (HNLs) are simple and well-motivated extensions of the Standard Model. In searches for HNLs in proton fixed-target experiments, we find that a large population of gauge bosons (Z′) produced by proton bremsstrahlung may decay to HNLs, leading to a significant improvement in existing bounds on the (mHNL,Uα), where Uα represent the mixing between HNL and the active neutrinos with flavor α. We study this possibility in fixed target experiments with the 8 GeV proton beams, including SBND, MicroBooNE, and ICARUS, as well as DUNE and DarkQuest at 120 GeV. We find the projected sensitivities to additional Z′-mediated HNL production can bring the seesaw mechanism of the neutrino masses within a broadened experimental reach.New gauge bosons coupled to heavy neutral leptons (HNLs) are simple and well-motivated extensions of the Standard Model. In searches for HNLs in proton fixed-target experiments, we find that a large population of gauge bosons () produced by proton bremsstrahlung may decay to HNLs, leading to a significant improvement in existing bounds on the (), where represent the mixing between HNL and the active neutrinos with flavor . We study this possibility in fixed target experiments with the 8 GeV proton beams, including SBND, MicroBooNE, and ICARUS, as well as DUNE and DarkQuest at 120 GeV. We find the projected sensitivities to additional -mediated HNL production can bring the seesaw mechanism of the neutrino masses within a broadened experimental reach
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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