22 research outputs found
Conversions between barycentric, RKFUN, and Newton representations of rational interpolants
We derive explicit formulas for converting between rational interpolants in
barycentric, rational Krylov (RKFUN), and Newton form. We show applications of
these conversions when working with rational approximants produced by the AAA
algorithm [Y. Nakatsukasa, O. S\`ete, L. N. Trefethen, arXiv preprint
1612.00337, 2016] within the Rational Krylov Toolbox and for the solution of
nonlinear eigenvalue problems
Oxidative Radical Transnitrilation of Arylboronic Acids with Trityl Isocyanide
We report a radical transnitrilation of arylboronic acids
with
trityl isocyanide in the presence of manganese(III) acetate. Many
functional groups can be tolerated in this transformation, and a special
positive effect of benzoic acid in this reaction has been observed
Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer
<p>HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic Y<u>C</u>DGFYA<u>C</u>YMDV-NH<sub>2</sub> (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDY<u>C</u>DGFYA<u>C</u>YMDV-NH<sub>2</sub>, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX <i>via</i> a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as <i>in vitro</i> model systems and nude mice with BT474 xenografts as an <i>in vivo</i> model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower <i>in vitro</i> IC<sub>50</sub>, and its <i>in vivo</i> extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.</p
Significant SNPs and each one's associated phenotype numbers at the significance level of .
<p>Top 3 SNP-phenotype associations are listed with corresponding P-values.</p
Comparison of the Manhattan plots for genome-wide p-values for phenotype volume of right inferior lateral ventricle from longitudinal analysis (left) and cross-sectional analysis (right); SNP rs429358 is not included.
<p>Comparison of the Manhattan plots for genome-wide p-values for phenotype volume of right inferior lateral ventricle from longitudinal analysis (left) and cross-sectional analysis (right); SNP rs429358 is not included.</p
The number (percentage) of non-missing observations at each time point in Figure 1.
<p>The number (percentage) of non-missing observations at each time point in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102312#pone-0102312-g001" target="_blank">Figure 1</a>.</p
The baseline characteristics of 638 subjects, including gender, age, years of education, handedness (R/L) and intracranial volume (ICV).
<p>P-values were calculated to test for differences among the diagnostic groups, HC, MCI and AD.</p
Comparison of the Q-Q plots without (left) or with (right) top 10 PCs.
<p>Comparison of the Q-Q plots without (left) or with (right) top 10 PCs.</p
The numbers of the significant SNP-phenotype associations at various levels of false discovery rate (FDR).
<p>The numbers of the significant SNP-phenotype associations at various levels of false discovery rate (FDR).</p
Comparison of the Manhattan plots without (left) or with (right) top 10 PCs.
<p>Comparison of the Manhattan plots without (left) or with (right) top 10 PCs.</p