Effect of internal and external conditions on ionization processes in the FAPA ambient desorption/ionization source

Ambient desorption/ionization (ADI) sources coupled to mass spectrometry (MS) offer outstanding analytical features: direct analysis of real samples without sample pretreatment, combined with the selectivity and sensitivity of MS. Since ADI sources typically work in the open atmosphere, ambient conditions can affect the desorption and ionization processes. Here, the effects of internal source parameters and ambient humidity on the ionization processes of the flowing atmospheric pressure afterglow (FAPA) source are investigated. The interaction of reagent ions with a range of analytes is studied in terms of sensitivity and based upon the processes that occur in the ionization reactions. The results show that internal parameters which lead to higher gas temperatures afforded higher sensitivities, although fragmentation is also affected. In the case of humidity, only extremely dry conditions led to higher sensitivities, while fragmentation remained unaffected.     

Extremal loading of soft fibrous tissues: multi-scale mechanics and constitutive modeling

In the current contribution, we present a multi-scale constitutive model capturing macroscopic inelastic effects (like stress softening and permanent set) in soft tissues under cyclic loading. Soft biological tissues can be described as a biological composite material. The extracellular matrix is hereby reinforced by collagen fibers which themself are an assembly of collagen fibrils embedded in a proteoglycan (PG) rich matrix. Micro-damage induced by cyclic loading is treated by an interaction scenario between the fibrils and the PGs. At the low strain regime PGs promote sliding between fibrils [1] which leads to the yielding of statistical distributed overlapping segments. The breakage of the PG-bridges is defined by a decreasing PG-density. Due to the accumulated damage of the PG connections at high tissue strains, the strains at the fibril level increases. This finally drives the over-stretching of the fibrils, which is associated with a permanent rupture of the hydrogen bonds inside of the tropocollagen molecules [2]. The so obtained model is in line with recent experimental findings [1, 2] and was additionally validated against experimental data available in literature. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

q value and parent energy optimization using a low-voltage ionization approach increases resolution in linear ion trap mass spectrometry

In this work, the isolation step in the linear ion trap was performed using different “q values” conditions at a low collision-induced dissociation (CID) energy leading to the parent ion resolution improvements, reasonably due to better ion energy distribution. According to the results, we obtained a greater resolution and mass accuracy operating in both traditional electrospray and low voltage ionization near the q value = 0.778 and with a CID energy of 10%. This effect was evaluated with low-molecular-mass compounds (skatole and arginine). The proposed optimization yielded a superior instrument performance without adding technological complexity to mass spectrometry analyses.     

Total Synthesis of Resveratrone and iso-Resveratrone

The first total synthesis of resveratrone and iso-resveratrone based on an epoxide olefination approach is described. The pivotal reaction proceeds by insertion of the lithiated epoxide into a boronic ester and subsequent syn-elimination. Resveratrone has been described to have remarkable photophysical properties, including two-photon absorption. Therefore, an azide derivative has been prepared to allow for use as a biological label.     

Photoinduced Aerobic Iodoarene‐Catalyzed Spirocyclization of N‐Oxy‐amides to N‐Fused Spirolactams**

Iodoarene catalysis is a powerful methodology that usually requires an excess of oxidant, or of redox mediator if the terminal oxidant is dioxygen, to generate the key hypervalent iodine intermediate to proceed efficiently. We report that, using the spiro‐cyclization of amides as a benchmark reaction, aerobic iodoarene catalysis can be enabled by relying on a pyrylium photocatalyst under blue light irradiation. This unprecedented dual organocatalytic system allows the use of low catalytic loading of both catalysts under very mild operating conditions.     

Synthesis,Antiprotozoal Activity,and Cheminformatic Analysis of 2-Phenyl-2H-Indazole Derivatives

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.     

Transport optimization on complex networks

We present a comparative study of the application of a recently introduced heuristic algorithm to the optimization of transport on three major types of complex networks. The algorithm balances network traffic iteratively by minimizing the maximum node betweenness with as little path lengthening as possible. We show that by using this optimal routing, a network can sustain significantly higher traffic without jamming than in the case of shortest path routing. A formula is proved and tested with numerical simulation that allows quick computation of the average number of hops along the path and of the average travel times once the betweennesses of the nodes are computed. Using this formula, we show that routing optimization preserves the small-world character exhibited by networks under shortest path routing, and that it significantly reduces the average travel time on congested networks with only a negligible increase in the average travel time at low loads. Finally, we study the correlation between the weights of the links in the case of optimal routing and the betweennesses of the nodes connected by them.     

3D MRI of non-Gaussian (3)He gas diffusion in the rat lung

In (3)He magnetic resonance images of pulmonary air spaces, the confining architecture of the parenchymal tissue results in a non-Gaussian distribution of signal phase that non-exponentially attenuates image intensity as diffusion weighting is increased. Here, two approaches previously used for the analysis of non-Gaussian effects in the lung are compared and related using diffusion-weighted (3)He MR images of mechanically ventilated rats. One approach is model-based and was presented by Yablonskiy et al., while the other approach utilizes the second order decay contribution that is predicted from the cumulant expansion theorem. Total lung coverage is achieved using a hybrid 3D pulse sequence that combines conventional phase encoding with sparse radial sampling for efficient gas usage. This enables the acquisition of nine 3D images using a total of only approximately 1 L of hyperpolarized (3)He gas. Diffusion weighting ranges from 0 s/cm(2) to 40 s/cm(2). Results show that the non-Gaussian effects of (3)He gas diffusion in healthy rat lungs are directly attributed to the anisotropic geometry of lung microstructure as predicted by the Yablonskiy model, and that quantitative analysis over the entire lung can be reliably repeated in time-course studies of the same animal.     

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

PURPOSE: The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment. RESULTS: Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model. CONCLUSION: The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.