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Hydrated transition metal ions are prototypical systems that can be used to model properties of transition metals in complex chemical environments. These seemingly simple systems present challenges for computational chemistry and are thus crucial in evaluations of quantum chemical methods for spin-state and redox energetics. In this work, we explore the applicability of the domain-based pair natural orbital implementation of coupled cluster (DLPNO-CC) theory to the calculation of ionization energies and redox potentials for hydrated ions of all first transition row (3d) metals in the 2+/3+ oxidation states, in connection with various solvation approaches. In terms of model definition, we investigate the construction of a minimally explicitly hydrated quantum cluster with a first and second hydration layer. We report on the convergence with respect to the coupled cluster expansion and the PNO space, as well as on the role of perturbative triple excitations. A recent implementation of the conductor-like polarizable continuum model (CPCM) for the DLPNO-CC approach is employed to determine self-consistent redox potentials at the coupled cluster level. Our results establish conditions for the convergence of DLPNO-CCSD(T) energetics and stress the absolute necessity to explicitly consider the second solvation sphere even when CPCM is used. The achievable accuracy for redox potentials of a practical DLPNO-based approach is, on average, 0.13 V. Furthermore, multilayer approaches that combine a higher-level DLPNO-CCSD(T) description of the first solvation sphere with a lower-level description of the second solvation layer are investigated. The present work establishes optimal and transferable methodological choices for employing DLPNO-based coupled cluster theory, the associated CPCM implementation, and cost-efficient multilayer derivatives of the approach for open-shell transition metal systems in complex environments.

A nearly linear scaling implementation of coupled-cluster with singles and doubles excitations (CCSD) can be achieved by means of the domain-based local pair natural orbital (DLPNO) method. The combination of DLPNO-CCSD with implicit solvation methods allows the calculation of accurate energies and chemical properties of solvated systems at an affordable computational cost. We have efficiently implemented different schemes within the conductor-like polarizable continuum model (C-PCM) for DLPNO-CCSD in the ORCA quantum chemistry suite. In our implementation, the overhead due to the additional solvent terms amounts to less than 5% of the time the equivalent gas phase job takes. Our results for organic neutrals and open-shell ions in water show that for most systems, adding solvation terms to the coupled-cluster amplitudes equations and to the energy leads to small changes in the total energy compared to only considering solvated orbitals and corrections to the reference energy. However, when the solute contains certain functional groups, such as carbonyl or nitrile groups, the changes in the energy are larger and estimated to be around 0.04 and 0.02 kcal/mol for each carbonyl and nitrile group in the solute, respectively. For solutes containing metals, the use of accurate CC/C-PCM schemes is crucial to account for correlation solvation effects. Simultaneously, we have calculated the electrostatic component of the solvation energy for neutrals and ions in water for the different DLPNO-CCSD/C-PCM schemes. We observe negligible changes in the deviation between DLPNO-CCSD and canonical-CCSD data. Here, DLPNO-CCSD results outperform those for Hartree-Fock and density functional theory calculations.

In urban contexts, the increasing density of electronic devices equipped with Global Navigation Satellite System (GNSS) receivers and complementary positioning technologies is attracting research and development efforts devoted to an improvement of the quality of life towards the smart city paradigm. Vehicular and pedestrian positioning and navigation capabilities are among the major drivers for innovation in this process. Ultra-low-cost electronics such as smartphones and Internet of Things (IoT) sensors aim at providing accurate and reliable positioning solutions through a set of promising solutions. Among these, snapshot positioning allows to remotely perform the post-processing of GNSS signals in IoT sensor networks while Wi-Fi&trade, ranging and cooperative positioning provide auxiliary anchors of opportunity to enhance indoor/outdoor positioning capabilities. This paper presents an innovative platform to perform a centralised testing and assessment of such positioning and navigation technologies along with a set of results obtained in the context of the European project HANSEL, by relying on current network technologies and infrastructures (i.e., Wi-Fi&trade, and cellular connectivity).

Herein, we provide new insights into the intermolecular interactions responsible for the intrinsic stability of the duplex structure of a large portion of human B-DNA by using advanced quantum mechanical methods. Our results indicate that (i) the effect of non-neighboring bases on the inter-strand interaction is negligibly small, (ii) London dispersion effects are essential for the stability of the duplex structure, (iii) the largest contribution to the stability of the duplex structure is the Watson–Crick base pairing – consistent with previous computational investigations, (iv) the effect of stacking between adjacent bases is relatively small but still essential for the duplex structure stability and (v) there are no cooperativity effects between intra-strand stacking and inter-strand base pairing interactions. These results are consistent with atomic force microscope measurements and provide the first theoretical validation of nearest neighbor approaches for predicting thermodynamic data of arbitrary DNA sequences., Advanced electronic structure methods provide a new insight into the intermolecular interactions responsible for the intrinsic stability of the duplex structure of human DNA.

Altres ajuts: ICREA Academia Award Background/objectives: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. Methods: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. Results: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. Conclusions: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity.

FLAMINGO is developing a service to facilitate for high accuracy positioning in smartphones and IOT devices. Currently, smartphones can only achieve accuracies of several meters at best, and IOT systems desire low power, connectivity, and a highly accurate location. FLAMINGO will deliver a service that targets sub-meter accuracies in both client- and server-side positioning scenarios. Through this, a new suite of location-based applications will be enabled, that were before infeasible, as well as enhancing existing location products. Substantial server infrastructure is developed to remove user GNSS knowledge needs, where an Application Program Interface (API) is provided to simplify integration. Modified PPP and RTK processing procedures are used to provide the high accuracy positioning.

In this work, we introduce a new way of improving the sligthly best performing global ionospheric model (GIM) within the International GNSS Service, the UQRG produced by UPC-IonSAT with the TOMION dual-layer voxel model solved with ground-based dual-frequency carrier phase GPS data combined with kriging interpolation. This is done by increasing its vertical resolution consistently with the heights of the now involved GNSS and DORIS LEO receivers. This has allowed the synergestic combination of vessel-, LEO- and ground-based measurements, providing an increase of the VTEC accuracy at global scale in large regions with sparse GPS ground-based data. The performance of the new resulting multiTOMION model is illustrated with a first application to one of the infrequent datasets, including the whole day of June 5, 2017, with all the involved input data collocated, in particular the vessel-based GNSS ones. The results show in particular: (1) an overall GIM improvement of 3% in standard deviation versus independent JASON-3 VTEC measurements when LEO- and ground- based GPS data are combined with DORIS measurements. And (2) a local improvement of 6–9% in performance versus observed differences of STEC from independent GPS receivers placed at several hundreds of km far from the vessel., This work has been developed thanks to the Atmosfiller project funded by the European Space Agency (ESA) and leaded by Rokubun S.L.

In this paper, a new methodology for the determination of the boundaries between oscillatory and non-oscillatory motion for nonviscously damped nonproportional systems is proposed. It is assumed that the damping forces are expressed as convolution integrals of the velocities via hereditary exponential kernels. Oscillatory motion is directly related to the complex nature of eigensolutions in a frequency domain and, in turn, on the value of the damping parameters. New theoretical results are derived on critical eigenmodes for viscoelastic systems with multiple degrees of freedom, with no restrictions on the number of hereditary kernels. Furthermore, these outcomes enable the construction of a numerical approach to draw the critical curves as solutions of certain parameter-dependent eigenvalue problems. The method is illustrated and validated through two numerical examples, covering discrete and continuous systems.

The shape control of nanoparticles constitutes one of the main challenges in today’s nanotechnology. The synthetic procedures are based on trial-and-error methods and are difficult to rationalize as many ingredients are typically used. For instance, concave nanoparticles exhibiting high-index facets can be obtained from Pt with different HCl treatments. These structures present exceptional capacities when are employed as catalysts in electrochemical processes, as they maximize the activity per mass unit of the expensive material. Here we show how atomistic simulations based on density functional theory that take into account the environment can predict the morphology for the nanostructures and how it is even possible to address the appearance of concave structures. To describe the control by etching, we have reformulated the Wulff construction through the use of a geometric model that leads to concave polyhedra, which have a larger surface-to-volume ratio compared to that for nanocubes. Such an increase makes these sorts of nanoparticles excellent candidates to improve electrocatalytic performance

The treatment of the solvation charges using Gaussian functions in the polarizable continuum model results in a smooth potential energy surface. These charges are placed on top of the surface of the solute cavity. In this article, we study the effect of the solute cavity (van der Waals-type or solvent-excluded surface-type) using the Gaussian charge scheme within the framework of the conductor-like polarizable continuum model on (a) the accuracy and computational cost of the self-consistent field (SCF) energy and its gradient and on (b) the calculation of free energies of solvation. For that purpose, we have considered a large set of systems ranging from few atoms to more than 200 atoms in different solvents. Our results at the DFT level using the B3LYP functional and the def2-TZVP basis set show that the choice of the solute cavity does neither affect the accuracy nor the cost of calculations for small systems (< 100 atoms). For larger systems, the use of a vdW-type cavity is recommended, as it prevents small oscillations in the gradient (present when using a SES-type cavity), which affect the convergence of the SCF energy gradient. Regarding the free energies of solvation, we consider a solvent-dependent probe sphere to construct the solvent-accessible surface area required to calculate the nonelectrostatic contribution to the free energy of solvation. For this part, our results for a large set of organic molecules in different solvents agree with available experimental data with an accuracy lower than 1 kcal/mol for both polar and nonpolar solvents.

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Nanoparticles are applied in a variety of industrially relevant transformations as heterogeneous catalysts typically with the help of an external force (pressure, temperature, or voltage) to steer the chemistry. The modification of platinum nanoparticles by a phosphate–amino surfactant enables catalysis without external energy supply in the hydrogenation of nitrobenzene to aniline. This can be attributed to the complex surfactant/metal interface which is able to split hydrogen into protons and electrons. The subsequent hydrogenation process mimics the electrochemical reduction described by Haber. The surfactant decorated Pt catalyst is two orders of magnitude more active than the state-of-the-art Pb-poisoned Pt catalyst. Our study provides a new approach to understand the functionality of emerging catalytic systems and can be applied to design new materials with optimal interfaces.

Continuum solvation models have become a widespread approach for the study of environmental effects in Density Functional Theory (DFT) methods. Adding solvation contributions mainly relies on the solution of the Generalized Poisson Equation (GPE) governing the behavior of the electrostatic potential of a system. Although multigrid methods are especially appropriate for the solution of partial differential equations, up to now, their use is not much extended in DFT-based codes because of their high memory requirements. In this Article, we report the implementation of an accelerated multigrid solver-based approach for the treatment of solvation effects in the Vienna ab initio Simulation Package (VASP). The stated implicit solvation model, named VASP-MGCM (VASP-Multigrid Continuum Model), uses an efficient and transferable algorithm for the product of sparse matrices that highly outperforms serial multigrid solvers. The calculated solvation free energies for a set of molecules, including neutral and ionic species, as well as adsorbed molecules on metallic surfaces, agree with experimental data and with simulation results obtained with other continuum models.

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This is a post-peer-review, pre-copyedit version of an article published in Gps solutions. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10291-018-0767-1 The number of existing global positioning system (GPS) single-frequency receivers continues growing. More than 90% of GPS receivers are implemented as low-cost single-frequency chipsets embedded in smartphones. This provides new opportunities, in particular for ionospheric sounding. In this context, we present the new sidereal days ionospheric graphic (SIg) combination of single-frequency GNSS measurements. SIg is able to monitor, for each given GNSS transmitter–receiver pair, the vertical total electron content (VTEC) relative to the previous observation with the same or almost the same line-of-sight (LOS) vector. In such arrangements the SIg multipath error mostly cancels, thus increasing the accuracy of the ¿VTEC significantly. This happens for the GPS constellation after one sidereal day (about 23 h 56 m) and for Galileo after 10 sidereal days approximately. Moreover, we show that the required calibration of the corresponding carrier phase ambiguity can be accurately performed by means of VTEC global ionospheric maps (GIMs). The results appear almost as accurate as those based on the dual-frequency technique, i.e., about 1 TECU or better, and with much more precision and resolution than the GIM values in the ionospheric region sounded by each given single-frequency receiver. The performance is demonstrated using actual data from 9 permanent GPS receivers during a total solar eclipse on August 21, 2017 over North America, where the corresponding ionospheric footprint is clearly detected in agreement with the total solar eclipse predictions. The advantages of extending SIg to lower carrier frequencies and the feasibility of applying it to other global navigation satellite system (GNSS) systems are also studied. This is shown in terms of a fully consistent VTEC depletion signature of the same eclipse phenomena, obtained with Galileo-only data in North America at mid and low latitude. Finally the SIg feasibility, including the cycle slip detection, is shown as well with actual mass-market single frequency GPS receivers at mid and high latitude.

Obesity and type 2 diabetes are strongly associated and a major health problem because of their alarmingly growing prevalence worldwide. The hypertrophic expansion of white adipose tissue (WAT) promotes ectopic fat accumulation and development of insulin resistance whereas WAT hyperplasia is associated with preservation of insulin sensitivity. Several members of the Bone Morphogenetic Protein (BMP) family have been shown to play a role in white and/or brown adipogenesis and energy homeostasis. Although BMP7 has extensively been reported to induce brown adipogenesis in vitro, its role on WAT expandability and its potential contribution to insulin sensitivity remains to be elucidated. Here, we showed that local administration of adeno-associated viral vectors (AAV) encoding BMP7 in WAT resulted in hyperplasic expansion of WAT together with reduced liver steatosis and amelioration of insulin sensitivity in both HFD-fed and ob/ob obese mice. In contrast, the AAV-mediated overexpression of BMP7 specifically in the liver did not promote WAT hyperplasia although the circulating levels of BMP7 achieved were similar to those obtained after intra-WAT administration of AAV vectors. Nevertheless, when liver-derived BMP7 circulating levels were further increased, body weight and insulin sensitivity were normalised in HFD-fed as well as in ob/ob mice. Altogether, these results unravel a new role of BMP7 on white adipogenesis. In addition, this study suggests the potential of BMP7 gene therapy to ameliorate obesity and insulin resistance. Disclosure E. Casana Lorente: None. V. Jimenez: None. V. Sacristán Fraile: None. S.A. Muñoz: None. C. Jambrina Pallarés: None. J. Rodó: None. S. Darriba: None. C. Mallol: None. M. Garcia: None. X. Leon: None. I. Grass: None. S. Franckhauser: None. F. Bosch: None.

The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function.

The selective C2 epimerization of the glucose/mannose pair on a set of Mo-based catalysts was studied by means of density functional theory. The process, known as the Bilik reaction, encompasses a 1,2 C-shift of the C3 centers at the sugars. Molybdic acid was initially proposed as a catalyst in this reaction, and recent experimental studies have shown that the polyoxometalate (POM) Keggin cluster H3PMo12O40 also presents a good performance. In the present work, we propose a reaction mechanism for the epimerization on the Keggin cluster with different heteroatoms and extend it to a larger POM, H6P2Mo18O62, and the continuous α-MoO3(010) surface. We have found that in the transition state corresponding to the 1,2 C-shift the Mo center acts as an electron buffer that promotes the transformation of the aldehyde group in C1 into an alkoxy group and the C2 alkoxy into an aldehyde group. As a consequence, the activity of Mo-containing compounds can be traced back to the reducibility of the Mo center and a simple microkinetic model illustrates that this descriptor generates an activity volcano. This allows the identification of a new POM that shall be 4.7 times more active than the parent compound. We have thus shown that continuum models linking the properties of molecular cluster-like catalysts and oxide surfaces can be derived and this paves the way towards a unified theory in catalysis.

The Radio Occultation instrument at the upcoming EUMETSAT Polar System – Second Generation (EPS-SG) mission will be devoted primarily to monitor the neutral atmosphere through this payload, consisting of a GNSS receiver and occultation antennae pointing slightly below the Earth's limb. The resulting data will be processed by EUMETSAT (primarily for L1B data) and by the ROMSAF's Radio Occultation Processing Package (ROPP) software to obtain the vertical profiles of temperature, pressure and other relevant level 2 parameters of the neutral atmosphere. Newer versions of this software might include a feature by which empirical models of the ionosphere (i.e. vertical profiles of electron density) can be included in the processing in order to increase the accuracy of the inverted bending angle profiles. In order to test this new feature, this work includes the efforts that have been made in order to provide an empirical model of the ionosphere purely based on vertical profiles of electron density inverted from data of previous radio occultation (RO) missions (i.e. COSMIC/FORMOSAT-3). The methodology used in this work is based on using the separability hypothesis, to overcome the spherical symmetry assumption of the Abel inversion as well as a new mechanization of the inversion process, based on a joint processing of all the occultation data via a linear mean square filter, rather than adopting the classical peel onion approach. Additionally, with the development of this empirical model, efforts have been made to construct a proxy index for scintillation monitoring based on the inverted profiles (Occultation Scintillation Proxy Index or OSPI), which shows reasonable correlation with the amplitude scintillation index S4.

Solvation is crucial in many chemical and electrochemical processes related to alcohol conversion on metal surfaces. Particularly, understanding the dehydrogenation mechanism of methanol on solvated Pd, Pt, and Ru surfaces could allow the design of efficient methanol fuel cells. The large computational cost related to adopting an explicit solvation approach into density functional theory can be reduced drastically by using implicit solvation methods. In this study, we use our recently developed continuum solvation model (MGCM) to elucidate the minimum number of explicit water molecules to add to the solvated methanol/metal surface systems to reproduce experimental data with an optimized balance between time and reliability. Our results stress the importance of adding two explicit water molecules, especially for the case of Ru surfaces. For this later system, we provide a first insight into the decomposition mechanism of methanol using first-principles calculations. Our predictions can be then a useful reference for future studies that aim at designing more efficient heterogeneous catalysts with solvents.

Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have distinct cognitive enhancement effects, it remains unclear whether their amplitudes can be independently enhanced. Furthermore, demands for top-down attention control, postural restraint and maintenance of cognitive set processes, all requiring low-beta frequencies, might masquerade as learning and confound interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes was investigated with the addition of a random frequency control condition that also requires the potentially confounding cognitive processes. A comprehensive approach to assessing neurofeedback learning was undertaken through the calculation of learning indices within- and across-session and pre-to-post baseline. Herein we provide the first demonstration of beta1 within-session amplitude learning that was not attributable to extraneous cognitive processes, for it was not found with random frequency training. On the other hand, within-session SMR learning might have been obscured by high interindividual variability and methodological limitations such as the type of feedback screen, the insufficient number of sessions, and the exclusion of simultaneous theta and high-beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions in the three groups suggesting unspecific effects of neurofeedback in the low beta frequency band. Moreover, there was no clear evidence of frequency specificity associated with either SMR or beta1 training. Some methodological limitations may underpin the divergent results with previous studies.

The dynamics of water encapsulated in the well-known polyoxomolybdate nanocapsules of the type Mo-132 is studied through molecular dynamics simulations. Two different ligands, namely, formate and sulfate ligands, are considered as decoration of the inner surface of the capsule. In both cases it is found that 172 water molecules are trapped inside, 72 of which are coordination water molecules, and the remaining 100 form a water nanodrop whose properties are studied. We find that the dynamic behavior of the nanodrop is significantly different between the two types of capsules considered as they have different interiors. We argue that the commensurability of the sulfate ligand nanocapsule imposes a high degree of tetrahedrality that confers rigidity to the three-dimensional water network affecting the whole water nanodrop in the cavity. The formate ligand capsule, instead, permits additional degrees of freedom that confer the water nanodrop a more liquid-like behavior. The overall size of the inner cavity is of the order of 1 nm which is comparable to the crossover length observed for effects related to the rigidity of water layers in contact with hydrophobic molecules.(1) The results could stimulate the investigation of encapsulated water in the presently used capsule, the interior of which can be widely tuned (even from hydrophilic to hydrophobic) in context with the fact that knowledge about water under confined conditions is of extreme importance.

[1] This work evaluates various approaches to compute the second order ionospheric correction (SOIC) to Global Positioning System (GPS) measurements. When estimating the reference frame using GPS, applying this correction is known to primarily affect the realization of the origin of the Earth's reference frame along the spin axis (Z coordinate). Therefore, the Z translation relative to the International Terrestrial Reference Frame 2008 is used as the metric to evaluate various published approaches to determining the slant total electron content (TEC) for the SOIC: getting the slant TEC from GPS measurements, and using the vertical total electron content (TEC) given by a Global Ionospheric Model (GIM) to transform it to slant TEC via a mapping function. All of these approaches agree to 1 mm if the ionospheric shell height needed in GIM-based approaches is set to 600 km. The commonly used shell height of 450 km introduces an offset of 1 to 2 mm. When the SOIC is not applied, the Z axis translation can be reasonably modeled with a ratio of +0.23 mm/TEC units of the daily median GIM vertical TEC. Also, precise point positioning (PPP) solutions (positions and clocks) determined with and without SOIC differ by less than 1 mm only if they are based upon GPS orbit and clock solutions that have consistently applied or not applied the correction, respectively. Otherwise, deviations of few millimeters in the north component of the PPP solutions can arise due to inconsistencies with the satellite orbit and clock products, and those deviations exhibit a dependency on solar cycle conditions.

Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase–activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenic mice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against diet-induced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases.

The relationship between the homogeneous and heterogeneous phases of a catalyst is widely neglected in part due to the inherent differences between the experimental and theoretical techniques employed to study them. It is well- known that, under reaction conditions, many homogeneous catalysts deactivate and generate black metals (i.e., nano- particles). Simultaneously, heterogeneous catalysts tend to suffer of leaching processes under harsh conditions, which produce the formation of species in the homogeneous phase (i.e., volatile or organometallic species). To unravel the links between these two types of catalytic species, we have taken PdAu catalysts in the oxidation of crotyl alcohol to crotonaldehyde and investigated the reaction process for both homogeneous and heterogeneous phases. We show that the process is possible in both phases and, essentially, contains the same elementary steps. The results indicate that the homogeneous catalyst is slightly more active; however, the enhanced stability of the heterogeneous phase provides a better performance under relevant reaction conditions. Both catalytic systems are connected through two simple steps that can be computed: oxidative leaching and deposition. The oxidative leaching of the PdAu nanoparticles in the presence of dioxygen can produce Pd(II) monomeric species able to catalyze the alcohol oxidation in homogeneous conditions. After the reaction the reduced Pd(0) homogeneous catalyst is reabsorbed onto the PdAu nanoparticles, preventing the aggregation process. The present work shows that the full homogeneous/heterogeneous catalytic cycle can be analyzed in a holistic manner with computational techniques.

The 30 cationic {(Mo2O4)-O-V(acetate)}(+) units linking 12 negatively charged pentagonal "ligands," {(Mo-VI)-(Mo5O21)-O-VI(H2O)(6)}(6-) of the porous metal-oxide capsule, [{(Mo6O21)-O-VI(H2O)(6)}(12){(Mo2O4)-O-V(acetate)}(30)](42-) provide active sites for catalytic transformations of organic "guests". This is demonstrated using a well-behaved model reaction, the fully reversible cleavage and formation of methyl tert-butyl ether (MTBE) under mild conditions in water. Five independent lines of evidence demonstrate that reactions of the MTBE guests occur in the ca. 6 x 10(3) angstrom(3) interior of the spherical capsule. The Mo atoms of the {(Mo2O4)-O-V(acetate)}(+) linkers-spanning an ca. 3-nm truncated icosahedron-are sterically accessible to substrate, and controlled removal of their internally bound acetate ligands generates catalytically active {(Mo2O4)-O-V(H2O)(2)}(2+) units with labile water ligands, and Lewis- and Bronsted-acid properties. The activity of these units is demonstrating by kinetic data that reveal a first-order dependence of MTBE cleavage rates on the number of acetate-free {(Mo2O4)-O-V(H2O)(2)}(2+) linkers. DFT calculations point to a pathway involving both Mo(V) centers, and the intermediacy of isobutene in both forward and reverse reactions. A plausible catalytic cycle satisfying microscopic reversibility is supported by activation parameters for MTBE cleavage, deuterium and oxygen-18 labeling studies, and by reactions of deliberately added isobutene and of a water-soluble isobutene analog. More generally, pore-restricted encapsulation, ligand-regulated access to multiple structurally integral metal-centers, and options for modifying the microenvironment within this new type of nanoreactor, suggest numerous additional transformations of organic substrates by this and related molybdenum-oxide based capsules.

The structure and dynamics of water confined inside a polyoxomolybdate molecular cluster [{(Mo)Mo(5)O(21)(H(2)O)(6)}(12){Mo(2)O(4)(SO(4))}(30)](72-) metal oxide nanocapsule have been studied by means of molecular dynamics simulations under ambient conditions. Our results are compared to experimental data and theoretical analyses done in reverse micelles, for several properties. We observe that the characteristic three-dimensional hydrogen bond network present in bulk water is distorted inside the cavity where water organizes instead in concentric layered structures. Hydrogen bonding, tetrahedral order, and orientational distribution analyses indicate that these layers are formed by water molecules hydrogen bonded with three other molecules of the same structure. The remaining hydrogen bond donor/acceptor site bridges different layers as well as the whole structure with the hydrophilic inner side of the cavity. The most stable configuration of the layers is thus that of a buckyball with 12 pentagons and a variable number of hexagons. The geometrical constraints make it so that the bridges between the layers display a significant degree of frustration. The main modes of motion at short times are correlated fluctuations of the entire system with a characteristic frequency. Switches of water molecules between layers are rare events, due to the stability of the layers. At long times, the system shows a power law decay (pink noise) in properties like the fluctuations in the number of molecules in the structures and the total dipole moment. Such behavior has been attributed to the complex relaxation of the hydrogen bond network, and the exponents found are close to those encountered in bulk water for the relaxation of the potential energy. Our results reveal the importance of the competition between the confinement and the long-range structure induced in this system by the hydrogen bond network.

High-Mobility-Group-A1 (HMGA1) proteins are non-histone proteins that regulate chromatin structure and gene expression during embryogenesis, tumourigenesis and immune responses. In vitro studies suggest that HMGA1 proteins may be required to regulate adipogenesis. To examine the role of HMGA1 in vivo, we generated transgenic mice overexpressing HMGA1 in adipose tissues. HMGA1 transgenic mice showed a marked reduction in white and brown adipose tissue mass that was associated with downregulation of genes involved in adipogenesis and concomitant upregulation of preadipocyte markers. Reduced adipogenesis and decreased fat mass were not associated with altered glucose homeostasis since HMGA1 transgenic mice fed a regular-chow diet exhibited normal glucose tolerance and insulin sensitivity. However, when fed a high-fat diet, overexpression of HMGA1 resulted in decreased body-weight gain, reduced fat mass, but improved insulin sensitivity and glucose tolerance. Although HMGA1 transgenic mice exhibited impaired glucose uptake in adipose tissue due to impaired adipogenesis, the increased glucose uptake observed in skeletal muscle may account for the improved glucose homeostasis. Our results indicate that HMGA1 plays an important function in the regulation of white and brown adipogenesis in vivo and suggests that impaired adipocyte differentiation and decreased fat mass is not always associated with impaired whole-body glucose homeostasis.