Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na⁺ adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na⁺/K⁺ ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na⁺ and K⁺ adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results.

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A biocatalytic approach to synthesizing optically active orthogonally protected trans-cyclopentane-1,2-diamine derivatives

A straightforward chemoenzymatic synthesis of optically active trans-N,N-dialkylcyclopentane-1,2-diamines has been efficiently developed starting out from their analogous (+/-)-trans-2-(N,N-dialkylamino)cyclopentanols. The route involves the one-pot stereospecific transformation of the racemic amino alcohols into racemic diamines and a subsequent kinetic resolution by means of lipase-B from Candida antarctica-catalyzed acylation reactions. The careful selection of both the alkyl substituents present in the diamine and the derivatization strategy applied to the enzymatic reaction enabled the easy preparation of other synthetically valuable optically active trans-cyclopentane-1,2-diamines derivatives.     

Algebra of Efficient Sets for Multiobjective Complex Systems

Complex systems are modeled as collections of multiobjective programs representing interacting subsystems of the overall system. Since the calculation of efficient sets of these complex systems is challenging, it is desirable to decompose the overall system into component multiobjective programs, that are more easily solved and then construct the efficient set of the overall system. For some classes of complex systems, algebraic properties of set operations and relations are developed between the efficient set of the overall system and the efficient sets of subproblems. The properties indicate that multiple decomposition and coordination schemes, with varying assumptions regarding the system, may be applied to the same initial system.     

Analysis of the vaporization process in TG apparatus and its incidence in pyrolysis

An analysis of the evaporation process of n-hexadecane in a thermogravimetric apparatus was carried out. n-Hexadecane represents a typical example of a high boiling point compound and its study is interesting for understanding those processes where vaporization takes place in parallel with pyrolysis during thermal treatment. The process has been studied under different operating conditions: nitrogen and air atmospheres, and isothermal and dynamic runs with three different heating rates from 5 K/min to 20 K/min. The experimental data were satisfactorily correlated to a n-order model with zero process order and the same apparent activation energy for all runs, but the exponential factors of the different runs depended on the initial mass and the heating rate. The experimental results were compared with those predicted considering the diffusion process inside the crucible, taking into account the vapor pressure and the diffusion coefficient of n-hexadecane. A parameter, product of these two variables, can be estimated from a single TG run, so the vaporization process in other equipment and/or operating conditions can also be estimated.     

Bis-amidocarbazolyl urea receptor for short-chain dicarboxylate anions

Urea receptor 1 based on two (1-amino-8-amido-3,6-dichloro)carbazole units shows a strong association with dicarboxylate anions such as oxalate, malonate and succinate guests through multiple hydrogen bonds from the carbazole, urea and amide NH groups. (1)H NMR complexation studies exhibit high values of association constants in DMSO-d(6). X-ray structures of the 1?:?1 complexes of 1 with oxalate and malonate as their ditetrabutylammonium salts were obtained. A modelling study of the complex of receptor 1 with succinate (as its diTBA salt) showed a more reduced geometric complementarity than its homologue malonate.     

Statistical anisotropy from vector curvaton in D-brane inflation

We investigate the possibility of embedding the vector curvaton paradigm in D-brane models of inflation in type IIB string theory in a simple toy model. The vector curvaton is identified with the U(1)$U(1)$ gauge field that lives on the world volume of a D3-brane, which may be stationary or undergoing general motion in the internal space. The dilaton is considered as a spectator field which modulates the evolution of the vector field. In this set-up, the vector curvaton is able to generate measurable statistical anisotropy in the spectrum and bispectrum of the curvature perturbation assuming that the dilaton evolves as e^−?∝a²$e^{-?}\propto a^2$ where a(t)$a(t)$ is the scale factor. Our work constitutes a first step towards exploring how such distinctive features may arise from the presence of several light fields that naturally appear in string theory models of cosmology.     

Acute and chronic MRI changes in the spine and spinal cord after surgical stem cell grafting in patients with definite amyotrophic lateral sclerosis: Post-infusion injuries are unrelated with clinical impairment

ObjectiveTo report MRI spinal changes after surgical infusion of bone marrow stem cells (BMSc) in ALS patients and assess their correlation with clinical events and functional performance.MethodsBMSc were surgically injected in the thoracic spinal cord of 11 ALS patients (6/5 male/female; median age 46 years). We performed first-week and third, sixth, ninth and twelfth post-surgical months spinal MRIs. The spinal changes in the postsurgical week and follow-up MRIs, as well as clinical events, functional scales and respiratory and electromyography data, were longitudinally monitored. Correlations between the imaging and clinical data were evaluated with the Spearman's test.ResultsTransient extradural fluid collections (100%), transient spinal cord T2 hyperintensity (81.8%), and chronic spinal cord deformities (63.6%) were the dominating MRI changes. Spinal cord hemorrhages (27.3%) and cystic myelomalacia (1/11 patients) were important although unusual findings. During the follow-up, minor adverse events of mild to moderate intensity eventually improved. Initial and follow-up imaging scores showed a strongly positive correlation (r 0.879, P < 0.001). The initial and delayed clinical scores did not correlate. There was no significant correlation between any of the imaging scores and clinical data.ConclusionsInfusion of BMSc produces a variety of spinal changes apparently unrelated with clinical events and disease worsening.     

Analysis of trans fatty acids production and squalene variation during amaranth oil extraction

The purpose of this study was to evaluate the decay of squalene and the formation of trans fatty acids (TFAs) in the amaranth oil extracted with hexane with and without heat. Oils were analyzed by determining their chemical values, and the fatty acids were identified and quantified by using Fourier-transform infrared (FTIR) spectroscopy, in the mid-region of 400?C4000 cm^?1, and gas chromatography. The FTIR analysis shows that two oil extracts (with and without heat) present a well-defined peak at 968 cm^?1, which represents the trans double bonds. The quantified TFAs are <0.5 g per 100 g of oil, which is considered as TFAs-free. The squalene content in the oil extracted without and with heat are 6.98±1.1% and 7.12±1.3%, respectively. Our data suggest that the TFAs formation is directly promoted by thermal processing and that squalene content is not affected by the application of heat during the oil extraction process in amaranth.      

Xanthone Receptors as Oxyanion‐Hole Mimics in Artificial Enzymes

Different xanthone‐based receptors ( 2 – 10 ) for lactones and lactams have been prepared, and the feasibility of these compounds to mimic the known enzymatic ‘oxyanion‐hole’ structure is discussed. The self‐association of the receptors was found to pose a serious drawback for complex formation. X‐Ray crystal structures of receptor dimers allowed us to understand the reasons for their self‐association and to improve the design of the catalysts. The catalytic activity of the receptors has been tested towards the nucleophilic addition of pyrrolidine to unsaturated lactones. Since the resulting complexes were very weak in organic solvents, new receptors were developed for lactams, which showed better stabilities, and their catalytic activities were studied.