Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids

The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η³-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC₅₀ values fall in the range 0.02–0.5 μm ). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η³-allyl fragment. The effectiveness of a representative complex, 4 c , was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids.     

Numerical study of the noninertial systems: application to train coupler systems

Car coupler forces have a significant effect on the longitudinal train dynamics and stability. Because the coupler inertia is relatively small in comparison with the car inertia; the high stiffness associated with the coupler components can lead to high frequencies that adversely impact the computational efficiency of train models. The objective of this investigation is to study the effect of the coupler inertia on the train dynamics and on the computational efficiency as measured by the simulation time. To this end, two different models are developed for the car couplers; one model, called the inertial coupler model, includes the effect of the coupler inertia, while in the other model, called the noninertial model, the effect of the coupler inertia is neglected. Both inertial and noninertial coupler models used in this investigation are assumed to have the same coupler kinematic degrees of freedom that capture geometric nonlinearities and allow for the relative translation of the draft gears and end of car cushioning (EOC) devices as well as the relative rotation of the coupler shank. In both models, the coupler kinematic equations are expressed in terms of the car body and coupler coordinates. Both the inertial and noninertial models used in this study lead to a system of differential and algebraic equations that are solved simultaneously in order to determine the coordinates of the cars and couplers. In the case of the inertial model, the coupler kinematics is described using the absolute Cartesian coordinates, and the algebraic equations describe the kinematic constraints imposed on the motion of the system. In this case of the inertial model, the constraint equations are satisfied at the position, velocity, and acceleration levels. In the case of the noninertial model, the equations of motion are developed using the relative joint coordinates, thereby eliminating systematically the algebraic equations that represent the kinematic constraints. A quasistatic force analysis is used to determine a set of coupler nonlinear force algebraic equations for a given car configuration. These nonlinear force algebraic equations are solved iteratively to determine the coupler noninertial coordinates which enter into the formulation of the equations of motion of the train cars. The results obtained in this study showed that the neglect of the coupler inertia eliminates high frequency oscillations that can negatively impact the computational efficiency. The effect of these high frequencies that are attributed to the coupler inertia on the simulation time is examined using frequency and eigenvalue analyses. While the neglect of the coupler inertia leads, as demonstrated in this investigation, to a much more efficient model, the results obtained using the inertial and noninertial coupler models show good agreement, demonstrating that the coupler inertia can be neglected without having an adverse effect on the accuracy of the solution.     

A resting state network in the motor control circuit of the basal ganglia

Background  

In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond.     

LC Separation and Online MS Characterization of Saturated and Unsaturated Alginic Acid Oligomers

We report the complete separation and characterization by online high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) of fully saturated alginic acid (AA) oligosaccharides from DP1 to beyond DP23, obtained by a chemical process, and unsaturated oligomers from DP1 to DP10, produced by lyase treatment. A series of negatively charged species of different m/z ratio are seen for each oligosaccharide. Smaller AA species, from DP1 to DP4, mainly furnish [M–H]^? anions whereas the DP5 to DP9-10 oligomers predominantly exist as the 2- charge state. The AA oligomers from DP10 to DP17 are mainly represented by the [M–3H]^3? anions whereas species from DP18 to DP23 are characterized by the 4? charge state. Online LC-ESI-MS enabled separation and simultaneous characterization of complex saturated and unsaturated AA oligomer mixtures without previous sample treatment, in particular extensive removal of salts to obtain species compatible with ESI-MS.     

On the Positive Parts of Second Order Symmetric Pseudodifferential Operators

Using microlocalization, the positive and the negative parts for a class of second order formally self-adjoint pseudodifferential operators are constructed.      

Strength vs. toughness optimization of microstructured composites

Aim of this paper is to present a new fractal approach linking the macroscopic mechanical properties of micro- and nano-structured materials with the main parameters: composition, grain size and structural dimension, as well as contiguity and mean free path. Assuming the key role played by the interfaces, the proposed fractal energy approach unifies the influences of all the above parameters, through the introduction of a fractal structural parameter (FSP), which represents an extension of the Gurland’s structural parameter. This modeling approach is assessed through an extensive comparison with experimental data on poly crystalline diamond (PCD) and WC–Co alloys. The results clearly show that the theoretical fractal predictions are in a fairly good agreement with the experiments on both hardness and toughness. This new synthetic parameter is thus proposed to investigate, design and optimize new micro- and nano-grained materials. Eventually, FSP-based optimization maps are developed, that allow to design new materials with high hardness and toughness.     

Urea Unfolding of Opsin in Phospholipid Bicelles†

Opsin is the unstable apo‐protein of the light‐activated G protein‐coupled receptor rhodopsin. We investigated the stability of bovine opsin, solubilized in 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC)/detergent bicelles, against urea‐induced unfolding. A single irreversible protein unfolding transition was observed from changes in intrinsic tryptophan fluorescence and far‐UV circular dichroism. This unfolding transition correlated with loss of protein activity. Changes in tertiary structure, as indicated by fluorescence measurements, were concomitant with an approximate 50% reduction in α‐helical content of opsin, indicating that global unfolding had been induced by urea. The urea concentration at the midpoint of unfolding was dependent on the lipid/detergent environment, occurring at approximately 1.2 m urea in DMPC/1,2‐dihexanoyl‐sn‐glycero‐3‐phosphocholine bicelles, while being significantly stabilized to approximately 3.5 m urea in DMPC/3‐[(cholamidopropyl)dimethylammonio]‐1‐propanesulfonate bicelles. These findings demonstrate that interactions with the surrounding lipids and detergent are highly influential in the unfolding of membrane protein structure. The urea/bicelle system offers the possibility for a more detailed understanding of the structural changes that take place upon irreversible unfolding of opsin.     

3-Quasi-Sasakian manifolds

We correct the results in section 6 of [B. Cappelletti Montano, A. De Nicola, G. Dileo, 3-Quasi-Sasakian manifolds, Ann. Global Anal. Geom. 33 (2008), 397–409], concerning the corrected energy of the Reeb distribution of a compact 3-quasi-Sasakian manifold. The results are slightly different than what was originally claimed and they are obtained by using results in [B. Cappelletti Montano, A. De Nicola, G. Dileo, The geometry of a 3-quasi-Sasakian manifold, Int. J. Math., to appear, arXiv:0801.1818], where the geometry of these manifolds is more deeply investigated. The online version of the original article can be found under doi:.     

On the shape factor of interaction laws for a non-local approximation of the Sobolev norm and the total variation

We consider the family of non-local and non-convex functionals introduced by H. Brézis and H.-M. Nguyen in a recent paper. These functionals Gamma-converge to a multiple of the Sobolev norm or the total variation, depending on a summability exponent, but the exact values of the constants are unknown in many cases.We describe a new approach to the Gamma-convergence result that leads in some special cases to the exact value of the constants, and to the existence of smooth recovery families.