Mass spectrometry fingerprinting coupled to National Institute of Standards and Technology Mass Spectral search algorithm for pattern recognition

A new analytical strategy based on mass spectrometry fingerprinting combined with the NIST-MS search program for pattern recognition is evaluated and validated. A case study dealing with the tracing of the geographical origin of virgin olive oils (VOOs) proves the capabilities of mass spectrometry fingerprinting coupled with NIST-MS search program for classification. The volatile profiles of 220 VOOs from Liguria and other Mediterranean regions were analysed by secondary electrospray ionization-mass spectrometry (SESI-MS). MS spectra of VOOs were classified according to their origin by the freeware NIST-MS search v 2.0. The NIST classification results were compared to well-known pattern recognition techniques, such as linear discriminant analysis (LDA), partial least-squares discriminant analysis (PLS-DA), k-nearest neighbours (kNN), and counter-propagation artificial neural networks (CP-ANN). The NIST-MS search program predicted correctly 96% of the Ligurian VOOs and 92% of the non-Ligurian ones of an external independent data set; outperforming the traditional chemometric techniques (prediction abilities in the external validation achieved by kNN were 88% and 84% for the Ligurian and non-Ligurian categories respectively). This proves that the NIST-MS search software is a useful classification tool.     

Atomic imaging of atomic layer deposition oxide nucleation with trimethylaluminum on As-rich InGaAs(001) 2 × 4 vs Ga/In-rich InGaAs(001) 4 × 2

Formation of a contaminant free, flat, electrically passive interface to a gate oxide such as a-Al(2)O(3) is the critical step in fabricating III-V metal oxide semiconductor field effect transistors; while the bulk oxide is amorphous, the interface may need to be ordered to prevent electrical defect formation. A two temperature in situ cleaning process is shown to produce a clean, flat group III or group V rich InGaAs surface. The dependence of initial surface reconstruction and dosing temperature of the seeding of aluminum with trimethylaluminum dosing is observed to produce an ordered unpinned passivation layer on InGaAs(001)-(4 × 2) surface at sample temperatures below 190 °C. Conversely, the InGaAs(001)-(2 × 4) surface is shown to generate an unpinned passivation layer with a seeding temperature up to 280 °C. For both reconstructions, the chemical drive force is consistent with formation of As-Al-As bonds. The optimal seed layer protects the surface from background contamination.     

An ultrasonic array sensor for spacecraft leak direction finding

We have developed an ultrasonic array sensor useable for locating air leaks in manned spacecraft and have found that this sensor locates leaks in a 1-m² plate to within 2 cm. The sensor consists of a 63-element multiplexed array plus a reference element, all constructed from a single PZT disc and a printed circuit board. Cross-correlations of signals from the array elements with signals from the single reference element provide a measurement of the leak noise passing through the spacecraft skin under the array. A spatial Fourier transform reveals the dominant direction of propagation. Triangulation from multiple sensor locations can be used to find the source of the leak.     

(1)H-(13)C INEPT MAS NMR correlation experiments with (1)H-(1)H mediated magnetization exchange to probe organization in lipid biomembranes

Two-dimensional (1)H-(13)C INEPT MAS NMR experiments utilizing a (1)H-(1)H magnetization exchange mixing period are presented for characterization of lipid systems. The introduction of the exchange period allows for structural information to be obtained via (1)H-(1)H dipolar couplings but with (13)C chemical shift resolution. It is shown that utilizing a RFDR recoupling sequence with short mixing times in place of the more standard NOE cross-relaxation for magnetization exchange during the mixing period allowed for the identification and separation of close (1)H-(1)H dipolar contacts versus longer-range inter-molecular (1)H-(1)H dipolar cross-relaxation. These 2D INEPT experiments were used to address both intra- and inter-molecular contacts in lipid and lipid/cholesterol mixtures.     

Binding affinity of alkynes and alkenes to low-coordinate iron

We report the synthesis, spectroscopy, and structural characterization of iron-alkyne and -alkene complexes of the type L(Me)Fe(ligand) [L(Me) = bulky beta-diketiminate, ligand = HCCPh, EtCCEt, CH2CHPh, EtCHCHEt, HCC(p-C6H4OCH3), HCC(p-C6H4CF3)]. The neutral ligand exchanges rapidly at room temperature, and the equilibrium constants have been measured or estimated. The binding affinity toward the low-coordinate Fe follows the trend HCCPh > EtCCEt > CH2CHPh > EtCHCHEt approximately PPh3 > benzene > N2. This trend is consistent with a model in which pi back-bonding from the formally Fe(I) center is the dominant interaction in determining the relative binding affinities. In nitrogenase, alkynes are reduced while alkenes are unreactive, and this work suggests that the different binding affinities to low-coordinate Fe might explain the differential activity of the enzyme toward these two substrates.     

The use of recently described ionisation techniques for the rapid analysis of some common drugs and samples of biological origin

Three ionisation techniques that require no sample preparation or extraction prior to mass analysis have been used for the rapid analysis of pharmaceutical tablets and ointments. These methods were (i) the novel direct analysis in real time (DART), (ii) desorption electrospray ionisation (DESI), and (iii) desorption atmospheric pressure chemical ionisation (DAPCI). The performance of the three techniques was investigated for a number of common drugs. Significant differences between these approaches were observed. For compounds of moderate to low polarity DAPCI produced more effective ionisation. Accurate DESI and DAPCI tandem mass spectra were obtained and these greatly enhance the selectivity and information content of the experiment. The detection from human skin of the active ingredients from ointments is reported together with the detection of ibuprofen metabolites in human urine.     

Can the nearly conformal sextet gauge model hide the Higgs impostor?

New results are reported from large scale lattice simulations of a frequently discussed strongly interacting gauge theory with a fermion flavor doublet in the two-index symmetric (sextet) representation of the SU(3) color gauge group. We find that the chiral condensate and the mass spectrum of the sextet model are consistent with chiral symmetry breaking in the limit of vanishing fermion mass. In contrast, sextet fermion mass deformations of spectral properties are not consistent with leading conformal scaling behavior near the critical surface of a conformal theory. A recent paper could not resolve the conformal fixed point of the gauge coupling from the slowly walking scenario of a very small nearly vanishing β-function (DeGrand et al. [3]). It is argued that overall consistency with our new results is resolved if the sextet model is close to the conformal window, staying outside with a very small non-vanishing β-function. The model would exhibit then the simplest composite Higgs mechanism leaving open the possibility of a light scalar state with quantum numbers of the Higgs impostor. It would emerge as the pseudo-Goldstone dilaton state from spontaneous symmetry breaking of scale invariance. We will argue that even without association with the dilaton, the scalar Higgs-like state can be light very close to the conformal window. A new Higgs project of sextet lattice simulations is outlined to resolve these important questions.     

A rotaxane-based platform for tailoring the pharmacokinetics of cancer-targeted radiotracers

Radiolabelled monoclonal antibodies (mAbs) are a cornerstone of molecular diagnostic imaging and targeted radioimmunotherapy in nuclear medicine, but one of the major challenges in the field is to identify ways of reducing the radiation burden to patients. We reasoned that a rotaxane-based platform featuring a non-covalent mechanical bond between the radionuclide complex and the biologically active mAb could offer new ways of controlling the biophysical properties of cancer-specific radiotracers for positron emission tomography (PET). Herein, we present the photoradiosynthesis and characterisation of [⁸⁹Zr]ZrFe-[4]rotaxane-azepin-onartuzumab ([⁸⁹Zr]ZrFe-2), a unique rotaxane-antibody conjugate for PET imaging and quantification of the human hepatocyte growth factor receptor (c-MET). Multiple component self-assembly reactions were combined with simultaneous ⁸⁹Zr-radiolabelling and light-induced bioconjugation methods to give [⁸⁹Zr]ZrFe-2 in 15 ± 1% (n = 3) decay-corrected radiochemical yield, with >90% radiochemical purity, and molar activities suitable for PET imaging studies (>6.1 MBq mg⁻¹ of protein). Cellular assays confirmed the specificity of [⁸⁹Zr]ZrFe-2 binding to the c-MET receptor. Temporal PET imaging in athymic nude mice bearing subcutaneous MKN-45 gastric adenocarcinoma xenografts demonstrated specific binding of [⁸⁹Zr]ZrFe-2 toward c-MET in vivo, where tumour uptake reached 9.8 ± 1.3 %ID g⁻¹ (72 h, n = 5) in a normal group and was reduced by ∼56% in a control (blocking) group. Head-to-head comparison of the biodistribution and excretion profile of [⁸⁹Zr]ZrFe-2versus two control compounds, alongside characterisation of two potential metabolites, showed that the rotaxane-radiotracer has an improved clearance profile with higher tumour-to-tissue contrast ratios and reduced radiation exposure to critical (dose-limiting) organs including liver, spleen, and kidneys. Collectively, the experimental results suggested that non-covalent mechanical bonds between the radionuclide and mAb can be used to fine-tune the pharmacokinetic profile of supramolecular radiopharmaceuticals in ways that are simply not accessible when using traditional covalent design.

Mechanically interlocked rotaxanes are transformed into positron-emitting radiotracers for cancer biomarker imaging. Mechanical bonding offers new possibilities for controlling drug delivery, metabolism, and excretion profiles in vivo.