Ionic Fragmentation Mechanisms of 2,2,2‐Trifluoroethanol Following Excitation with Synchrotron Radiation

Gaseous 2,2,2‐trifluoroethanol (TFE) is excited with synchrotron radiation between 10 and 1000 eV and the ejected electrons and positive ions are detected in coincidence. In the valence‐electron energy region, the most abundant species is CH₂OH⁺. Other fragments, including ions produced by atomic rearrangements, are also detected; the most abundant are COH⁺, CFH₂⁺ and CF₂H₂⁺. The energies of electronic transitions from C 1 s, O 1 s and F 1 s orbitals to vacant molecular orbitals are determined. A site‐specific C 1 s excitation is observed. The photofragmentation mechanisms after the excitation of core‐shell electrons are inferred from analysis of the shape and slope of the coincidence between two charged fragments in the bi‐dimensional coincidence spectra. The spectra are dominated by islands that correspond to the coincidence of H⁺ with several charged fragments. One of the most important channels leads to the formation of CH₂OH⁺ and CF₃⁺ in a concerted mechanism.     

Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.

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Graphical abstract In this work, polymeric nanoparticles functionalized with a liver cancer-specific aptamer were examined as potential targeted drug delivery vehicles. The aptamer-functionalized nanoparticles were found to significantly improve doxorubicin drug delivery and cell-killing capacity in vitro versus non-targeted controls, supporting their use as a targeted treatment toward liver cancer tumors.

     

Optimization of Monte Carlo trial moves for protein simulations

Closed rigid-body rotations of residue segments under bond-angle restraints are simple and effective Monte Carlo moves for searching the conformational space of proteins. The efficiency of these moves is examined here as a function of the number of moving residues and the magnitude of their displacement. It is found that the efficiency of folding and equilibrium simulations can be significantly improved by tailoring the distribution of the number of moving residues to the simulation temperature. In general, simulations exploring compact conformations are more efficient when the average number of moving residues is smaller. It is also demonstrated that the moves do not require additional restrictions on the magnitude of the rotation displacements and perform much better than other rotation moves that do not restrict the bond angles a priori. As an example, these results are applied to the replica exchange method. By assigning distributions that generate a smaller number of moving residues to lower temperature replicas, the simulation times are decreased as long as the higher temperature replicas are effective.     

Drug encapsulation within self-assembled microglobules formed by thermoresponsive supramolecules

An 8-(phenyl)-2'-deoxyguanosine derivative self-assembles in aqueous media into discrete hexadecamers that further self-assemble above 32 °C into microglobules that encapsulate the drug doxorubicin.     

Strangeness enhancement in Cu-Cu and Au-Au collisions at √S(NN)=200 GeV

We report new STAR measurements of midrapidity yields for the Λ, Λ[over ˉ], K(S)(0), Ξ(-), Ξ[over ˉ](+), Ω(-), Ω[over ˉ](+) particles in Cu+Cu collisions at √S(NN)==200 GeV, and midrapidity yields for the Λ, Λ[over ˉ], K(S)(0) particles in Au+Au at √S(NN)==200 GeV. We show that, at a given number of participating nucleons, the production of strange hadrons is higher in Cu+Cu collisions than in Au+Au collisions at the same center-of-mass energy. We find that aspects of the enhancement factors for all particles can be described by a parametrization based on the fraction of participants that undergo multiple collisions.     

Influence of Ta,Y substitutions on the thermal stability,microhardness and magnetic properties of melt spun Fe–B–Si amorphous alloys

In the present research work, thermal stability, magnetic properties and microhardness of Fe₇₂B_19.2Si_4.8M₄ (M = Ta or Y) amorphous ribbons obtained by chill block melt-spinning technique are reported. The crystallization temperatures resulted as high as 1129 K (for M = Ta) and of 1167 K (for M = Y), which indicate a considerable thermal stability for both alloys. On the other hand, the saturation polarization (μ₀M_s) together with the Curie temperature (T_c) also showed excellent combination of values, with 0.95 ± 0.12 T and 586 ± 8 K, respectively (for the Ta-containing alloy) and of 1.55 ± 0.18 T and 698 ± 6 K, respectively (for the Y-containing alloy). Additionally, the Vickers microhardness exhibited values over 1100 kg/mm² for both alloys.     

Automated interpretation of low-energy collision-induced dissociation spectra by SeqMS, a software aid for de novo sequencing by tandem mass spectrometry

SeqMS, a software aid for de novo sequencing by tandem mass spectrometry (MS/MS), which was initially developed for the automated interpretation of high-energy collision-induced dissociation (CID) MS/MS spectra of peptides, has been applied to the interpretation of low-energy CID and post-source decay (PSD) spectra of peptides. Based on peptide backbone fragmented ions and their related ions, which are the dominant ions observed in the latter two techniques, the types of ions and their propensities to be observed have been optimized for efficient interpretation of the spectra. In a typical example, the modified SeqMS allowed the complete sequencing of a 31-amino acid synthetic peptide, except for the isobaric amino acids (Leu or Ile, and Lys or Gln), based on only the low-energy CID-MS/MS spectrum.     

Automated interpretation of mass spectra of complex mixtures by matching of isotope peak distributions

Mass spectrometry is now firmly established as a powerful technique for the identification and characterization of proteins when used in conjunction with sequence databases. Various approaches involving stable-isotope labeling have been developed for quantitative comparisons between paired samples in proteomic expression analysis by mass spectrometry. However, interpretation of such mass spectra is far from being fully automated, mainly due to the difficulty of analyzing complex patterns resulting from the overlap of multiple peaks arising from the assortment of natural isotopes. In order to facilitate the interpretation of a complex mass spectrum of such a mixture, such as an MS spectrum of a stable-isotope-enriched ion species, we report on the development of a software application, 'Matching' (web accessible), that enables the automatic matching of theoretical isotope envelopes to multiple ion peaks in a raw spectrum. It is particularly useful for resolving the relative abundances of narrow-split paired peaks caused by enrichment with a stable isotope, such as 18O, 13C, 2H, or 15N.