Molecular effect of an OPTN common variant associated to Paget's disease of bone

Paget's disease of bone (PDB) is a chronic bone disorder and although genetic factors appear to play an important role in its pathogenesis, to date PDB causing mutations were identified only in the Sequestosome 1 (SQSTM1) gene at the PDB3 locus. PDB6 locus, also previously linked to PDB, contains several candidate genes for metabolic bone diseases. We focused our analysis in the most significantly associated variant with PDB, within the Optineurin (OPTN) gene, i.e. the common variant rs1561570. Although it was previously shown to be strongly associated with PDB in several populations, its contribution to PDB pathogenesis remains unclear. In this study we have shown that rs1561570 may contribute to PDB since its Tallele results in the loss of a methylation site in patients' DNA, leading to higher levels of OPTN gene expression and a corresponding increase in protein levels in patients' osteoclasts. This increase in OPTN expression leads to higher levels of NF-KB translocation into the nucleus and increasing expression of its target genes, which may contribute to the overactivity of osteoclasts observed in PDB. We also reported a tendency for a more severe clinical phenotype in the presence of a haplotype containing the rs1561570 T allele, which appear to be re-enforced with the presence of the SQSTM1/P392L mutation. In conclusion, our work provides novel insight towards understanding the functional effects of this variant, located in OPTN intron 7, and its implication in the contribution to PDB pathogenesis.national funds from Foundation for Science and Technology (FCT) [UID/Multi/04326/2013]; Canadian Institutes for Health Research, Canada [MOP130457]; CHU de Quebec Foundation; Canadian Foundation for Innovation; Fonds de recherche du Quebec-sante; Laval University; CHU de Quebec-Universite Laval Research Centre; FCT [SFRH/BD/77227/2011, SFRH/BPD/111898/2015]; Fonds de recherche Quebec-Sante (FRQ-S), Quebec, Canad

Group classification of (1+1)-Dimensional Schr\"odinger Equations with Potentials and Power Nonlinearities

We perform the complete group classification in the class of nonlinear Schr\"odinger equations of the form $i\psi_t+\psi_{xx}+|\psi|^\gamma\psi+V(t,x)\psi=0$ where $V$ is an arbitrary complex-valued potential depending on $t$ and $x,$ $\gamma$ is a real non-zero constant. We construct all the possible inequivalent potentials for which these equations have non-trivial Lie symmetries using a combination of algebraic and compatibility methods. The proposed approach can be applied to solving group classification problems for a number of important classes of differential equations arising in mathematical physics.Comment: 10 page

Universal Heat Conduction in YBa_2Cu_3O_6.9

The thermal conductivity of YBa_2Cu_3O_6.9 was measured at low temperatures in untwinned single crystals with concentrations of Zn impurities from 0 to 3% of Cu. A linear term kappa_0/T = 0.19 mW/K^2.cm is clearly resolved as T -> 0, and found to be virtually independent of Zn concentration. The existence of this residual normal fluid strongly validates the basic theory of transport in unconventional superconductors. Moreover, the observed universal behavior is in quantitative agreement with calculations for a gap function of d-wave symmetry.Comment: Latex file, 4 pages, 3 EPS figures, to appear in Physical Review Letter

Evaluating elbow osteoarthritis within the prehistoric Tiwanaku state using generalized estimating equations (GEE).

OBJECTIVES:Studies of osteoarthritis (OA) in human skeletal remains can come with scalar problems. If OA measurement is noted as present or absent in one joint, like the elbow, results may not identify specific articular pathology data and the sample size may be insufficient to address research questions. If calculated on a per data point basis (i.e., each articular surface within a joint), results may prove too data heavy to comprehensively understand arthritic changes, or one individual with multiple positive scores may skew results and violate the data independence required for statistical tests. The objective of this article is to show that the statistical methodology Generalized Estimating Equations (GEE) can solve scalar issues in bioarchaeological studies. MATERIALS AND METHODS:Using GEE, a population-averaged statistical model, 1,195 adults from the core and one colony of the prehistoric Tiwanaku state (AD 500-1,100) were evaluated bilaterally for OA on the seven articular surfaces of the elbow joint. RESULTS:GEE linked the articular surfaces within each individual specimen, permitting the largest possible unbiased dataset, and showed significant differences between core and colony Tiwanaku peoples in the overall elbow joint, while also pinpointing specific articular surfaces with OA. Data groupings by sex and age at death also demonstrated significant variation. A pattern of elbow rotation noted for core Tiwanaku people may indicate a specific pattern of movement. DISCUSSION:GEE is effective and should be encouraged in bioarchaeological studies as a way to address scalar issues and to retain all pathology information

Transport Anomalies and the Role of Pseudogap in the "60-K Phase" of YBa_{2}Cu_{3}O_{7-\delta}

We report the result of our accurate measurements of the a- and b-axis resistivity, Hall coefficient, and the a-axis thermopower in untwinned YBa_{2}Cu_{3}O_{y} single crystals in a wide range of doping. It is found that both the a-axis resistivity and the Hall conductivity show anomalous dependences on the oxygen content y in the "60-K phase" below the pseudogap temperature T^*. The complete data set enables us to narrow down the possible pictures of the 60-K phase, with which we discuss a peculiar role of the pseudogap in the charge transport.Comment: 4 pages, 4 figures, accepted for publication in PR

Angular position of nodes in the superconducting gap of YBCO

The thermal conductivity of a YBCO single crystal has been studied as a function of the relative orientation of the crystal axes and a magnetic field rotating in the Cu-O planes. Measurements were carried out at several temperatures below T_c and at a fixed field of 30 kOe. A four-fold symmetry characteristic of a superconducting gap with nodes at odd multiples of 45 degrees in k-space was resolved. Experiments were performed to exclude a possible macroscopic origin for such a four-fold symmetry such as sample shape or anisotropic pinning. Our results impose an upper limit of 10% on the weight of the s-wave component of the essentially d-wave superconducting order parameter of YBCO.Comment: 10 pages, 4 figure

Fluid-Induced Propulsion of Rigid Particles in Wormlike Micellar Solutions

In the absence of inertia, a reciprocal swimmer achieves no net motion in a viscous Newtonian fluid. Here, we investigate the ability of a reciprocally actuated particle to translate through a complex fluid that possesses a network using tracking methods and birefringence imaging. A geometrically polar particle, a rod with a bead on one end, is reciprocally rotated using magnetic fields. The particle is immersed in a wormlike micellar (WLM) solution that is known to be susceptible to the formation of shear bands and other localized structures due to shear-induced remodeling of its microstructure. Results show that the nonlinearities present in this WLM solution break time-reversal symmetry under certain conditions, and enable propulsion of an artificial "swimmer." We find three regimes dependent on the Deborah number (De): net motion towards the bead-end of the particle at low De, net motion towards the rod-end of the particle at intermediate De, and no appreciable propulsion at high De. At low De, where the particle time-scale is longer then the fluid relaxation time, we believe that propulsion is caused by an imbalance in the fluid first normal stress differences between the two ends of the particle (bead and rod). At De~1, however, we observe the emergence of a region of network anisotropy near the rod using birefringence imaging. This anisotropy suggests alignment of the micellar network, which is "locked in" due to the shorter time-scale of the particle relative to the fluid

Soil weathering rates in 21 catchments of the Canadian Shield

Soil mineral weathering represents an essential source of nutrient base cation (Ca, Mg and K) for forest growth in addition to provide a buffering power against precipitation acidity for soils and surface waters. Weathering rates of base cations were obtained for 21 catchments located within the temperate and the boreal forest of the Canadian Shield with the geochemical model PROFILE. Weathering rates ranged from 0.58 to 4.46 kmol<sub>c</sub> ha<sup>−1</sup> yr<sup>−1</sup> and their spatial variation within the studied area was mostly in agreement with spatial variations in soil mineralogy. Weathering rates of Ca and Mg were significantly correlated (<i>r</i> = 0.80 and 0.64) with their respective lake concentrations. Weathering rates of K and Na did not correlate with lake concentrations of K and Na. The modeled weathering rates for each catchment were also compared with estimations of net catchment exportations. The result show that modeled weathering rates of Ca were not significantly different than the net catchment exportations while modeled weathering rates of Mg were higher by 51%. Larger differences were observed for K and Na weathering rates that were significantly different than net catchment exportations being 6.9 and 2.2 times higher than net exportations, respectively. The results for K were expected given its high reactivity with biotic compartments and suggest that most of the K produced by weathering reactions was retained within soil catchments and/or above ground biomass. This explanation does not apply to Na, however, which is a conservative element in forest ecosystems because of the insignificant needs of Na for soil microorganisms and above ground vegetations. It raises concern about the liability of the PROFILE model to provide reliable values of Na weathering rates. Overall, we concluded that the PROFILE model is powerful enough to reproduce spatial geographical gradients in weathering rates for relatively large areas as well as adequately predict absolute weathering rates values for the sum of base cations, Ca and Mg

Helmholtz bright and boundary solitons

We report, for the first time, exact analytical boundary solitons of a generalized cubic-quintic Non-Linear Helmholtz (NLH) equation. These solutions have a linked-plateau topology that is distinct from conventional dark soliton solutions; their amplitude and intensity distributions are spatially delocalized and connect regions of finite and zero wave-field disturbances (suggesting also the classification as 'edge solitons'). Extensive numerical simulations compare the stability properties of recently-reported Helmholtz bright solitons, for this type of polynomial non-linearity, to those of the new boundary solitons. The latter are found to possess a remarkable stability characteristic, exhibiting robustness against perturbations that would otherwise lead to the destabilizing of their bright-soliton counterpart

Heterotic Models from Vector Bundles on Toric Calabi-Yau Manifolds

We systematically approach the construction of heterotic E_8 X E_8 Calabi-Yau models, based on compact Calabi-Yau three-folds arising from toric geometry and vector bundles on these manifolds. We focus on a simple class of 101 such three-folds with smooth ambient spaces, on which we perform an exhaustive scan and find all positive monad bundles with SU(N), N=3,4,5 structure groups, subject to the heterotic anomaly cancellation constraint. We find that anomaly-free positive monads exist on only 11 of these toric three-folds with a total number of bundles of about 2000. Only 21 of these models, all of them on three-folds realizable as hypersurfaces in products of projective spaces, allow for three families of quarks and leptons. We also perform a preliminary scan over the much larger class of semi-positive monads which leads to about 44000 bundles with 280 of them satisfying the three-family constraint. These 280 models provide a starting point for heterotic model building based on toric three-folds.Comment: 41 pages, 5 figures. A table modified and a table adde