Dual-Functionalized PAMAM Dendrimers with Improved P‑Glycoprotein Inhibition and Tight Junction Modulating Effect

This study aims to surface modify poly­(amido amine) or PAMAM dendrimers by sequentially grafting poly­(ethylene glycol) or PEG and 4-thiobutylamidine (TBA) so as to reduce PAMAM cytotoxicity while improving the ability of PAMAM to modulate P-glycoprotein (P-gp) efflux and tight junction integrity. Conjugation of functional groups was determined by NMR spectroscopy, FT-IR, thiol group quantification and molecular weight estimation. The yield of the dual-functionalized dendrimers was >80%. The dual-functionalized dendrimer could significantly reduce PAMAM cytotoxicity to <15% as reflected by LDH release in Caco-2 and MDCK/MDR1 cells after 72 h of exposure. Thiolated dendrimers could increase cellular accumulation and permeation of the P-gp substrate R-123, and such effect could be affected by the extent of PEGylation of the dendrimer. Surface-modified PAMAM dendrimers, either by single or dual functionalization, could better modulate tight junction integrity in comparison with unmodified PAMAM, as demonstrated through immunostaining of the tight junction marker ZO-1, permeation of the model compound Lucifer Yellow (LY) and transepithelial electrical resistance (TEER). Of importance, reversible tight junction modulating effect was only observed in the dual-functionalized dendrimers. Collectively, dual functionalization with PEG and TBA represented a promising approach in altering PAMAM dendrimer surface for potential application in oral drug delivery

Dual-functionalized PAMAM dendrimers with improved P-glycoprotein inhibition and tight junction modulating effect

10.1021/bm401057cBiomacromolecules14124226-4235BOMA

Multiplicity and transverse-momentum dependence of two- and four-particle correlations in pPb and PbPb collisions

Measurements of two- and four-particle angular correlations for charged particles emitted in pPb collisions are presented over a wide range in pseudorapidity and full azimuth. The data, corresponding to an integrated luminosity of approximately 31 inverse nanobarns, were collected during the 2013 LHC pPb run at a nucleon-nucleon center-of-mass energy of 5.02 TeV by the CMS experiment. The results are compared to 2.76 TeV semi-peripheral PbPb collision data, collected during the 2011 PbPb run, covering a similar range of particle multiplicities. The observed correlations are characterized by the near-side (abs(Delta(phi)~0) associated pair yields and the azimuthal anisotropy Fourier harmonics (v[n]). The second-order (v[2]) and third-order (v[3]) anisotropy harmonics are extracted using the two-particle azimuthal correlation technique. A four-particle correlation method is also applied to obtain the value of v[2] and further explore the multi-particle nature of the correlations. Both associated pair yields and anisotropy harmonics are studied as a function of particle multiplicity and transverse momentum. The associated pair yields, the four-particle v[2], and the v[3] become apparent at about the same multiplicity. A remarkable similarity in the v[3] signal as a function of multiplicity is observed between the pPb and PbPb systems. Predictions based on the color glass condensate and hydrodynamic models are compared to the experimental results

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present