Interaction of tRNA with Eukaryotic Ribosome

This paper is a review of currently available data concerning interactions of tRNAs with the eukaryotic ribosome at various stages of translation. These data include the results obtained by means of cryo-electron microscopy and X-ray crystallography applied to various model ribosomal complexes, site-directed cross-linking with the use of tRNA derivatives bearing chemically or photochemically reactive groups in the CCA-terminal fragment and chemical probing of 28S rRNA in the region of the peptidyl transferase center. Similarities and differences in the interactions of tRNAs with prokaryotic and eukaryotic ribosomes are discussed with concomitant consideration of the extent of resemblance between molecular mechanisms of translation in eukaryotes and bacteria.     

Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines

Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam₃CysSK₄. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.     

Size Effects on the Mechanical Properties of Nanoporous Graphene Networks

It is essential to understand the size scaling effects on the mechanical properties of graphene networks to realize the potential mechanical applications of graphene assemblies. Here, a “highly dense‐yet‐nanoporous graphene monolith (HPGM)” is used as a model material of graphene networks to investigate the dependence of mechanical properties on the intrinsic interplanar interactions and the extrinsic specimen size effects. The interactions between graphene sheets could be enhanced by heat treatment and the plastic HPGM is transformed into a highly elastic network. A strong size effect is revealed by in situ compression of micro‐ and nanopillars inside electron microscopes. Both the modulus and strength are drastically increased as the specimen size reduces to ≈100 nm, because of the reduced weak links in a small volume. Molecular dynamics simulations reveal the deformation mechanism involving slip‐stick sliding, bending, buckling of graphene sheets, collapsing, and densification of graphene cells. In addition, a size‐dependent brittle‐to‐ductile transition of the HPGM nanopillars is discovered and understood by the competition between volumetric deformation energy and critical dilation energy.     

Direct Optical Patterning of Quantum Dot Light-Emitting Diodes via In Situ Ligand Exchange

Precise patterning of quantum dot (QD) layers is an important prerequisite for fabricating QD light-emitting diode (QLED) displays and other optoelectronic devices. However, conventional patterning methods cannot simultaneously meet the stringent requirements of resolution, throughput, and uniformity of the pattern profile while maintaining a high photoluminescence quantum yield (PLQY) of the patterned QD layers. Here, a specially designed nanocrystal ink is introduced, “photopatternable emissive nanocrystals” (PENs), which satisfies these requirements. Photoacid generators in the PEN inks allow photoresist-free, high-resolution optical patterning of QDs through photochemical reactions and in situ ligand exchange in QD films. Various fluorescence and electroluminescence patterns with a feature size down to ≈1.5 µm are demonstrated using red, green, and blue PEN inks. The patterned QD films maintain ≈75% of original PLQY and the electroluminescence characteristics of the patterned QLEDs are comparable to thopse of non-patterned control devices. The patterning mechanism is elucidated by in-depth investigation of the photochemical transformations of the photoacid generators and changes in the optical properties of the QDs at each patterning step. This advanced patterning method provides a new way for additive manufacturing of integrated optoelectronic devices using colloidal QDs.     

Adaptive reshaping of objects in (multiparameter) Hilbert space for enhanced detection and classification: an application of receiver operating curve statistics to laser-based mass spectroscopy

We propose a new approach to the classical detection problem of discrimination of a true signal of interest from an interferent signal, which may be applied to the area of chemical sensing. We show that the detection performance, as quantified by the receiver operating curve (ROC), can be substantially improved when the signal is represented by a multicomponent data set that is actively manipulated by means of a shaped laser probe pulse. In this case, the signal sought (agent) and the interfering signal (interferent) are visualized by vectors in a multidimensional detection space. Separation of these vectors can be achieved by adaptive modification of a probing laser pulse to actively manipulate the Hamiltonian of the agent and interferent. We demonstrate one implementation of the concept of adaptive rotation of signal vectors to chemical agent detection by means of strong-field time-of-flight mass spectrometry.     

Temperature-tuning of near-infrared monodisperse quantum dot solids at 1.5 microm for controllable forster energy transfer

We present the first time-resolved cryogenic observations of Forster energy transfer in large, monodisperse lead sulfide quantum dots with ground-state transitions near 1.5 microm (0.8 eV), in environments from 160 K to room temperature. The observed temperature-dependent dipole-dipole transfer rate occurs in the range of (30-50 ns) (-1), measured with our confocal single-photon counting setup at 1.5 microm wavelengths. By temperature-tuning the dots, 94% efficiency of resonant energy transfer can be achieved for donor dots. The resonant transfer rates match well with proposed theoretical models.     

Targeted tumor cell internalization and imaging of multifunctional quantum dot-conjugated immunoliposomes in vitro and in vivo

Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages in the development and application of nanomedicines. To incorporate the unique optical properties of luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis and treatment, we describe the synthesis, biophysical characterization, tumor cell-selective internalization, and anticancer drug delivery of QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic properties and in vivo imaging capability of QD-ILs were also investigated. Freeze-fracture electron microscopy was used to visualize naked QDs, liposome controls, nontargeted QD-conjugated liposomes (QD-Ls), and QD-ILs. QD-ILs prepared by insertion of anti-HER2 scFv exhibited efficient receptor-mediated endocytosis in HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells but not in control MCF-7 cells as analyzed by flow cytometry and confocal microscopy. In contrast, nontargeted QD-Ls showed minimal binding and uptake in these cells. Doxorubicin-loaded QD-ILs showed efficient anticancer activity, while no cytotoxicity was observed for QD-ILs without chemotherapeutic payload. In athymic mice, QD-ILs significantly prolonged circulation of QDs, exhibiting a plasma terminal half-life ( t 1/2) of approximately 2.9 h as compared to free QDs with t 1/2 < 10 min. In MCF-7/HER2 xenograft models, localization of QD-ILs at tumor sites was confirmed by in vivo fluorescence imaging.     

Transverse susceptibility method in nanoparticulate magnetic media

Transverse susceptibility (TS) method is a reliable method for the determination of anisotropy in nanoparticulate media. To correctly evaluate the value of anisotropy in various modern nanostructured materials, a number of theoretical problems related to the method have to be well understood to avoid significant systematic errors. This paper presents the state of the art in the TS method which includes the expression for single domain particles with any type of anisotropy, the theoretical and micromagnetic, using Landau-Lifshitz-Gilbert (LLG) equation and stochastic LLG equation studies of the effects of ac field amplitude, inter-particle interactions, and magnetic relaxation. The problem of both real and imaginary parts of the TS signal is also discussed.     

Catalytic Activity of Thallium on Electrochemical Degradation of Metronidazole from Aqueous Solutions

The platinum/thallium electrode was prepared by thallium electrodeposition on platinum substrate in order to use it for the increase of the electrochemical degradation rate of some drugs, such as, in our study, metronidazole (MNZ). The platinum/thallium electrode was characterized by chronoamperometry, electrochemical impedance spectroscopy (EIS), and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. 2D progressive nucleation mechanism of thallium layer development was found by chronoamperometry. The value of charge transfer resistance of 537.2 Ω cm² and the double-layer capacitance value of 2.9 mF cm^?2 were deduced by EIS. The scanning electron microscopy showed a relatively fine-grained structure and the uniform distribution of the thallium granules. The electrochemical degradation of metronidazole has been performed using galvanostatic technique associated with UV-Vis spectrophotometry. The degradation degree of metronidazole reached a higher level on platinum/thallium electrode than that on platinum plate, indicating its improved performance and electrocatalytic activity of thallium coating. Moreover, the electrochemical degradation mechanism of this drug was proposed, the best way to fit the experimental data being the kinetics model of the first-order reactions.