Laser Beam Filtration for High Spatial Resolution MALDI Imaging Mass Spectrometry

We describe an easy and inexpensive way to provide a highly defined Gaussian shaped laser spot on target of 5 μm diameter for imaging mass spectrometry using a commercial MALDI TOF instrument that is designed to produce a 20 μm diameter laser beam on target at its lowest setting. A 25 μm pinhole filter on a swivel arm was installed in the laser beam optics outside the vacuum ion source chamber so it is easily flipped into or out of the beam as desired by the operator. The resulting ion images at 5 μm spatial resolution are sharp since the satellite secondary laser beam maxima have been removed by the filter. Ion images are shown to demonstrate the performance and are compared with the method of oversampling to achieve higher spatial resolution when only a larger laser beam spot on target is available.

Calix[4]arenes as molecules for second order nonlinear optics

Abstract

The synthesis of a novel class of molecules for second order nonlinear optics, i.e. calix[4]arenes with extended π-systems, is described. These compounds are obtained via Wittig-Horner reactions of the formylated calix[4]arenes 5 and 6 to give the stilbene derivatives 7–9, or by diazotization of calix[4]arene, 1, followed by alkylation to give the phenylazocalix[4]arenes 11 and 12. The molecular second order nonlinear optical properties (β_z) of these calix[4]arenes have been measured by electric field-induced second harmonic generation. The influence of different acceptors as well as the influence of the different conformations of the calix[4]arenes on β_z values were determined. Surprisingly, the wavelength of the charge-transfer band λ_max is lower when β_z increases upon increasing the number of acceptors.     

Ultrasonic approach for formation of erbium oxide nanoparticles with variable geometries

Ultrasound (20 kHz, 29 W·cm(-2)) is employed to form three types of erbium oxide nanoparticles in the presence of multiwalled carbon nanotubes as a template material in water. The nanoparticles are (i) erbium carboxioxide nanoparticles deposited on the external walls of multiwalled carbon nanotubes and Er(2)O(3) in the bulk with (ii) hexagonal and (iii) spherical geometries. Each type of ultrasonically formed nanoparticle reveals Er(3+) photoluminescence from crystal lattice. The main advantage of the erbium carboxioxide nanoparticles on the carbon nanotubes is the electromagnetic emission in the visible region, which is new and not examined up to the present date. On the other hand, the photoluminescence of hexagonal erbium oxide nanoparticles is long-lived (μs) and enables the higher energy transition ((4)S(3/2)-(4)I(15/2)), which is not observed for spherical nanoparticles. Our work is unique because it combines for the first time spectroscopy of Er(3+) electronic transitions in the host crystal lattices of nanoparticles with the geometry established by ultrasound in aqueous solution of carbon nanotubes employed as a template material. The work can be of great interest for "green" chemistry synthesis of photoluminescent nanoparticles in water.     

Single-molecule force spectroscopy of β-peptides that display well-defined three-dimensional chemical patterns

Oligomers of β-amino acids ("β-peptides") can be designed to fold into stable helices that display side chains with a diverse range of chemical functionality in precise arrangements. We sought to determine whether the predictable, three-dimensional side-chain patterns generated by β-peptides could be used in combination with single-molecule force spectroscopy to quantify how changes in nanometer-scale chemical patterns affect intermolecular interactions. To this end, we synthesized β-peptides that were designed to be either globally amphiphilic (GA), i.e., display a global segregation of side chains bearing hydrophobic and cationic functional groups, or non-globally amphiphilic (iso-GA), i.e., display a more uniform distribution of hydrophobic and cationic functional groups in three-dimensions. Single-molecule force measurements of β-peptide interactions with hydrophobic surfaces through aqueous solution (triethanolamine buffer, pH 7.2) reveal that the GA and iso-GA isomers give rise to qualitatively different adhesion force histograms. The data are consistent with the display of a substantial nonpolar domain by the GA oligomer, which leads to strong hydrophobic interactions, and the absence of a comparable domain on the iso-GA oligomer. This interpretation is supported by force measurements in the presence of methanol, which is known to disrupt hydrophobic interactions. Our ability to associate changes in measured forces with changes in three-dimensional chemical nanopatterns projected from conformationally stable β-peptide helices highlights a contrast between this system and conventional peptides (α-amino acid residues): conventional peptides are more conformationally flexible, which leads to uncertainty in the three-dimensional nanoscopic chemical patterns that underlie measured forces. Overall, we conclude that β-peptide oligomers provide a versatile platform for quantifying intermolecular interactions that arise from specific functional group nanopatterns.     

An improved lesion detection approach based on similarity measurement between fuzzy intensity segmentation and spatial probability maps

The application of automatic segmentation methods in lesion detection is desirable. However, such methods are restricted by intensity similarities between lesioned and healthy brain tissue. Using multi-spectral magnetic resonance imaging (MRI) modalities may overcome this problem but it is not always practicable. In this article, a lesion detection approach requiring a single MRI modality is presented, which is an improved method based on a recent publication. This new method assumes that a low similarity should be found in the regions of lesions when the likeness between an intensity based fuzzy segmentation and a location based tissue probabilities is measured. The usage of a normalized similarity measurement enables the current method to fine-tune the threshold for lesion detection, thus maximizing the possibility of reaching high detection accuracy. Importantly, an extra cleaning step is included in the current approach which removes enlarged ventricles from detected lesions. The performance investigation using simulated lesions demonstrated that not only the majority of lesions were well detected but also normal tissues were identified effectively. Tests on images acquired in stroke patients further confirmed the strength of the method in lesion detection. When compared with the previous version, the current approach showed a higher sensitivity in detecting small lesions and had less false positives around the ventricle and the edge of the brain.     

One-step synthesis of novel 2,4-diaminopyrimidine antifolates from bridged alicyclic ketones and cyanoguanidine

A convenient one-step reaction with cyanoguanidine was used to convert alicyclic ketones to previously undescribed 2,4-diamino-5,6,7,8-tetrahydroquinazolines with a one-, two-, or three-carbon bridge in the carbocyclic ring. Although the yields of the desired products were modest, the principal advantage of this one-step process was that it provided easy access to a variety of novel bridged heterocyclic ring systems whose synthesis from sterically hindered ketones by other methods would have required multiple steps with an even lower overall yield. The products were tested as inhibitors of dihydrofolate reductases from Pneumocystis carinii, Toxoplasma gondii, and rat liver with a view to examining the effect of a space-filling bridge on binding. The most potent and selective compound in the group was 4,6-diamino-3,5-diazatricyclo[7.2.1.0^2,7]dodeca-2,4,6-triene ( 13 ), whose potency and selectivity approached those of trimethoprim, a drug commonly used to treat P. carinii and T. gondii infection. 3,5-Diamino-4,6-diazatricyclo[6.2.1.0^2,7]-undeca-2,4,6-triene ( 14 ), the analog of 13 with a one-carbon rather than a two-carbon bridge showed similar potency and selectivity against the T. gondii enzyme, but was a weak and nonselective inhibitor of P. carinii dihydrofolate reductase. The other compounds tested were likewise weak and nonselective.     

MicroRNA Delivery by Graphene-Based Complexes into Glioblastoma Cells

Glioblastoma (GBM) is the most common primary and aggressive tumour in brain cancer. Novel therapies, despite achievements in chemotherapy, radiation and surgical techniques, are needed to improve the treatment of GBM tumours and extend patients’ survival. Gene delivery therapy mostly uses the viral vector, which causes serious adverse events in gene therapy. Graphene-based complexes can reduce the potential side effect of viral carries, with high efficiency of microRNA (miRNA) or antisense miRNA delivery to GBM cells. The objective of this study was to use graphene-based complexes to induce deregulation of miRNA level in GBM cancer cells and to regulate the selected gene expression involved in apoptosis. The complexes were characterised by Fourier transform infrared spectroscopy (FTIR), scanning transmission electron microscopy and zeta potential. The efficiency of miRNA delivery to the cancer cells was analysed by flow cytometry. The effect of the anticancer activity of graphene-based complexes functionalised by the miRNA sequence was analysed using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide salt (XTT) assays at the gene expression level. The results partly explain the mechanisms of miRNA deregulation stress, which is affected by graphene-based complexes together with the forced transport of mimic miR-124, miR-137 and antisense miR-21, -221 and -222 as an anticancer supportive therapy.