Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

Phylogenetic position of the acariform mites: sensitivity to homology assessment under total evidence

Background: Mites (Acari) have traditionally been treated as monophyletic, albeit composed of two major lineages: Acariformes and Parasitiformes. Yet recent studies based on morphology, molecular data, or combinations thereof, have increasingly drawn their monophyly into question. Furthermore, the usually basal (molecular) position of one or both mite lineages among the chelicerates is in conflict to their morphology, and to the widely accepted view that mites are close relatives of Ricinulei. Results: The phylogenetic position of the acariform mites is examined through employing SSU, partial LSU sequences, and morphology from 91 chelicerate extant terminals (forty Acariformes). In a static homology framework, molecular sequences were aligned using their secondary structure as guide, whereby regions of ambiguous alignment were discarded, and pre-aligned sequences analyzed under parsimony and different mixed models in a Bayesian inference. Parsimony and Bayesian analyses led to trees largely congruent concerning infraordinal, well-supported branches, but with low support for inter-ordinal relationships. An exception is Solifugae + Acariformes (P. P = 100%, J. = 0.91). In a dynamic homology framework, two analyses were run: a standard POY analysis and an analysis constrained by secondary structure. Both analyses led to largely congruent trees; supporting a (Palpigradi (Solifugae Acariformes)) clade and Ricinulei as sister group of Tetrapulmonata with the topology (Ricinulei (Amblypygi (Uropygi Araneae))). Combined analysis with two different morphological data matrices were run in order to evaluate the impact of constraining the analysis on the recovered topology when employing secondary structure as a guide for homology establishment. The constrained combined analysis yielded two topologies similar to the exclusively molecular analysis for both morphological matrices, except for the recovery of Pedipalpi instead of the (Uropygi Araneae) clade. The standard (direct optimization) POY analysis, however, led to the recovery of trees differing in the absence of the otherwise well-supported group Solifugae + Acariformes. Conclusions: Previous studies combining ribosomal sequences and morphology often recovered topologies similar to purely morphological analyses of Chelicerata. The apparent stability of certain clades not recovered here, like Haplocnemata and Acari, is regarded as a byproduct of the way the molecular homology was previously established using the instrumentalist approach implemented in POY. Constraining the analysis by a priori homology assessment is defended here as a way of maintaining the severity of the test when adding new data to the analysis. Although the strength of the method advocated here is keeping phylogenetic information from regions usually discarded in an exclusively static homology framework; it still has the inconvenience of being uninformative on the effect of alignment ambiguity on resampling methods of clade support estimation. Finally, putative morphological apomorphies of Solifugae + Acariformes are the reduction of the proximal cheliceral podomere, medial abutting of the leg coxae, loss of sperm nuclear membrane, and presence of differentiated germinative and secretory regions in the testis delivering their products into a common lumen.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.

CHARACTERIZATION OF EXPONENTIAL DIVERGENCE OF THE KALMAN FILTER FOR TIME-VARYING SYSTEMS

This paper studies semistability of the recursive Kalman filter in the context of linear time-varying (LTV), possibly nondetectable systems with incorrect noise information. Semistability is a key property, as it ensures that the actual estimation error does not diverge exponentially. We explore structural properties of the filter to obtain a necessary and sufficient condition for the filter to be semistable. The condition does not involve limiting gains nor the solution of Riccati equations, as they can be difficult to obtain numerically and may not exist. We also compare semistability with the notions of stability and stability w.r.t. the initial error covariance, and we show that semistability in a sense makes no distinction between persistent and nonpersistent incorrect noise models, as opposed to stability. In the linear time invariant scenario we obtain algebraic, easy to test conditions for semistability and stability, which complement results available in the context of detectable systems. Illustrative examples are included.

Synchrotron X-ray powder diffraction and extended X-ray absorption fine structure spectroscopy studies on nanocrystalline ZrO(2)-CaO solid solutions

The crystal structure and the local atomic order of a series of nanocrystalline ZrO(2)-CaO solid solutions with varying CaO content were studied by synchrotron radiation X-ray powder diffraction and extended X-ray absorption fine structure (EXAFS) spectroscopy. These samples were synthesized by a pH-controlled nitrate-glycine gel-combustion process. For CaO contents up to 8 mol%, the t' form of the tetragonal phase (c/a > 1) was identified, whereas for 10 and 12 mol% CaO, the t '' form (c/a=1; oxygen anions displaced from their ideal positions in the cubic phase) was detected. Finally, the cubic phase was observed for solid solutions with CaO content of 14 mol% CaO or higher. The t'/t '' and t ''/cubic compositional boundaries were determined to be at 9 (1) and 13 (1) mol% CaO, respectively. The EXAFS study demonstrated that this transition is related to a tetragonal-to-cubic symmetry change of the first oxygen coordination shell around the Zr atoms.

Systematic studies of elliptic flow measurements in Au plus Au collisions at s(NN)=200 GeV

We present inclusive charged hadron elliptic flow (v(2)) measured over the pseudorapidity range vertical bar eta vertical bar < 0.35 in Au+Au collisions at s(NN)=200 GeV. Results for v(2) are presented over a broad range of transverse momentum (p(T)=0.2-8.0 GeV/c) and centrality (0-60%). To study nonflow effects that are correlations other than collective flow, as well as the fluctuations of v(2), we compare two different analysis methods: (1) the event-plane method from two independent subdetectors at forward (vertical bar eta vertical bar=3.1-3.9) and beam (vertical bar eta vertical bar>6.5) pseudorapidities and (2) the two-particle cumulant method extracted using correlations between particles detected at midrapidity. The two event-plane results are consistent within systematic uncertainties over the measured p(T) and in centrality 0-40%. There is at most a 20% difference in the v(2) between the two event-plane methods in peripheral (40-60%) collisions. The comparisons between the two-particle cumulant results and the standard event-plane measurements are discussed.

Stability, causality, and quasinormal modes of cosmic strings and cylinders

In this work we consider the evolution of a massive scalar field in cylindrically symmetric space-times. Quasinormal modes have been calculated for static and rotating cosmic cylinders. We found unstable modes in some cases. Rotating as well as static cosmic strings, i.e., without regular interior solutions, do not display quasinormal oscillation modes. We conclude that rotating cosmic cylinder space-times that present closed timelike curves are unstable against scalar perturbations.

Topology Studies of Hydrodynamics Using Two-Particle Correlation Analysis

The effects of fluctuating initial conditions are studied in the context of relativistic heavy ion collisions where a rapidly evolving system is formed. Two-particle correlation analysis is applied to events generated with the NEXSPHERIO hydrodynamic code, starting with fluctuating nonsmooth initial conditions (IC). The results show that the nonsmoothness in the IC survives the hydroevolution and can be seen as topological features of the angular correlation function of the particles emerging from the evolving system. A long range correlation is observed in the longitudinal direction and in the azimuthal direction a double peak structure is observed in the opposite direction to the trigger particle. This analysis provides clear evidence that these are signatures of the combined effect of tubular structures present in the IC and the proceeding collective dynamics of the hot and dense medium.

Phase transitions and regions of stability in Reissner-Nordstrom holographic superconductors

The phase transition of Reissner-Nordstrom AdS(4) interacting with a massive charged scalar field has been further revisited. We found exactly one stable and one unstable quasinormal mode region for the scalar field. The two of them are separated by the first marginally stable solution.

Experimental studies of di-jet survival and surface emission bias in Au plus Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at the BNL Relativistic Heavy Ion Collider (RHIC). Pairs of back-to-back high-transverse-momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two-and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudorapidity Delta eta or relative azimuthal angle Delta phi from d + Au to central Au + Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.

Gravitational stability of simply rotating Myers-Perry black holes: Tensorial perturbations

We study the stability of D >= 7 asymptotically flat black holes rotating in a single two-plane against tensor-type gravitational perturbations. The extensive search of quasinormal modes for these black holes did not indicate any presence of growing modes, implying the stability of simply rotating Myers-Perry black holes against tensor-type perturbations.

Stability of higher dimensional Reissner-Nordstrom-anti-de Sitter black holes

We investigate stability of the D-dimensional Reissner-Nordstrom-anti-de Sitter metrics as solutions of the Einstein-Maxwell equations. We have shown that asymptotically anti-de Sitter (AdS) black holes are dynamically stable for all values of charge and anti-de Sitter radius in D=5,6...11 dimensional space-times. This does not contradict dynamical instability of RNAdS black holes found by Gubser in N=8 gauged supergravity, because the latter instability comes from the tachyon mode of the scalar field, coupled to the system. Asymptotically AdS black holes are known to be thermodynamically unstable for some region of parameters, yet, as we have shown here, they are stable against gravitational perturbations.

(In)stability of D-dimensional black holes in Gauss-Bonnet theory

We make an extensive study of evolution of gravitational perturbations of D-dimensional black holes in Gauss-Bonnet theory. There is an instability at higher multipoles l and large Gauss-Bonnet coupling alpha for D = 5, 6, which is stabilized at higher D. Although a small negative gap of the effective potential for the scalar type of gravitational perturbations exists for higher D and whatever alpha, it does not lead to any instability.

Detection of catechol using mixed Langmuir-Blodgett films of a phospholipid and phthalocyanines as voltammetric sensors

The combination of metallic phthalocyanines (MPcs) and biomolecules has been explored in the literature either as mimetic systems to investigate molecular interactions or as supporting layers to immobilize biomolecules. Here, Langmuir-Blodgett (LB) films containing the phospholipid dimyristoyl phosphatidic acid (DMPA) mixed either with iron phthalocyanine (FePc) or with lutetium bisphthalocyanine (LuPc(2)) were applied as ITO modified-electrodes in the detection of catechol using cyclic voltammetry. The mixed Langmuir films of FePc + DMPA and LuPc(2) + DMPA displayed surface-pressure isotherms with no evidence of molecular-level interactions. The Fourier Transform Infrared (FTIR) spectra of the multilayer LB films confirmed the lack of interaction between the components. The DMPA and the FePc molecules were found to be oriented perpendicularly to the substrate, while LuPc(2) molecules were randomly organized. The phospholipid matrix induced a remarkable electrocatalytic effect on the phthalocyanines; as a result the mixed LB films deposited on ITO could be used to detect catechol with detection limits of 4.30 x 10(-7) and 3.34 x 10(-7) M for FePc + DMPA and LuPc(2) + DMPA, respectively. Results from kinetics experiments revealed that ion diffusion dominated the response of the modified electrodes. The sensitivity was comparable to that of other non-enzymatic sensors, which is sufficient to detect catechol in the food industry. The higher stability of the electrochemical response of the LB films and the ability to control the molecular architecture are promising for further studies with incorporation of biomolecules.

Structural models for yttrium aluminium borate laser glasses: NMR and EPR studies of the system (Y(2)O(3))(0.2)-(Al(2)O(3))(x)-(B(2)O(3))(0.8-x)

The structure of laser glasses in the system (Y(2)O(3))(0.2){(Al(2)O(3))(x))(B(2)O(3))(0.8-x)} (0.15 <= x <= 0.40) has been investigated by means of (11)B, (27)Al, and (89)Y solid state NMR as well as electron spin echo envelope modulation (ESEEM) of Yb-doped samples. The latter technique has been applied for the first time to an aluminoborate glass system. (11)B magic-angle spinning (MAS)-NMR spectra reveal that, while the majority of the boron atoms are three-coordinated over the entire composition region, the fraction of three-coordinated boron atoms increases significantly with increasing x. Charge balance considerations as well as (11)B NMR lineshape analyses suggest that the dominant borate species are predominantly singly charged metaborate (BO(2/2)O(-)), doubly charged pyroborate (BO(1/2)(O(-))(2)), and (at x = 0.40) triply charged orthoborate groups. As x increases along this series, the average anionic charge per trigonal borate group increases from 1.38 to 2.91. (27)Al MAS-NMR spectra show that the alumina species are present in the coordination states four, five and six, and the fraction of four-coordinated Al increases markedly with increasing x. All of the Al coordination states are in intimate contact with both the three-and the four-coordinate boron species and vice versa, as indicated by (11)B/(27)Al rotational echo double resonance (REDOR) data. These results are consistent with the formation of a homogeneous, non-segregated glass structure. (89)Y solid state NMR spectra show a significant chemical shift trend, reflecting that the second coordination sphere becomes increasingly ""aluminate-like'' with increasing x. This conclusion is supported by electron spin echo envelope modulation (ESEEM) data of Yb-doped glasses, which indicate that both borate and aluminate species participate in the medium range structure of the rare-earth ions, consistent with a random spatial distribution of the glass components.