Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.

Ischemic Stroke in Young Adults

Stroke is the second leading cause of death and the leading cause of disability worldwide. Of all strokes, up to 80% to 85% are ischemic, and of these, less than 10% occur in young individuals. Stroke in young adults—most often defined as stroke occurring under the age of 45 or 50—can be particularly devastating due to long expected life-span ahead and marked socio-economic consequences. Current basic knowledge on ischemic stroke in this age group originates mostly from rather small and imprecise patient series. Regarding emergency treatment, systematic data on use of intravenous thrombolysis are absent. For this Thesis project, we collected detailed clinical and radiological data on all consecutive patients aged 15 to 49 with first-ever ischemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital. The aims of the study were to define demographic characteristics, risk factors, imaging features, etiology, and long-term mortality and its predictors in this patient population. We additionally sought to investigate, whether intravenous thrombolysis is safe and beneficial for the treatment of acute ischemic stroke in the young. Of our 1008 patients, most were males (ratio 1.7:1), who clearly outnumbered females after the age of 44, but females were preponderant among those aged <30. Occurrence increased exponentially. The most frequent risk factors were dyslipidemia (60%), smoking (44%), and hypertension (39%). Risk factors accumulated in males and along aging. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups, followed by small-vessel disease (14%), and large-artery atherosclerosis (8%). A total of 33% had undetermined etiology. Left hemisphere strokes were more common in general. Posterior circulation infarcts were more common among those aged <45. Multiple brain infarcts were present in 23% of our patients, 13% had silent infarcts, and 5% had leukoaraiosis. Of those with silent brain infarcts, majority (54%) had only a single lesion, and most of the silent strokes were located in basal ganglia (39%) and subcortical regions (21%). In a logistic regression analysis, type 1 diabetes mellitus in particular predicted the presence of both silent brain infarcts (odds ratio 5.78, 95% confidence interval 2.37-14.10) and leukoaraiosis (9.75; 3.39-28.04). We identified 48 young patients with hemispheric ischemic stroke treated with intravenous tissue plasminogen activator, alteplase. For comparisons, we searched 96 untreated control patients matched by age, gender, and admission stroke severity, as well as 96 alteplase-treated older controls aged 50 to 79 matched by gender and stroke severity. Alteplase-treated young patients recovered more often completely (27% versus 10%, P=0.010) or had only mild residual symptoms (40% versus 22%, P=0.025) compared to age-matched controls. None of the alteplase-treated young patients had symptomatic intracerebral hemorrhage or died within 3-month follow-up. Overall long-term mortality was low in our patient population. Cumulative mortality risks were 2.7% (95% confidence interval 1.5-3.9%) at 1 month, 4.7% (3.1-6.3%) at 1 year, and 10.7% (9.9-11.5%) at 5 years. Among the 30-day survivors who died during the 5-year follow-up, more than half died due to vascular causes. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large-artery atherosclerosis causing the index stroke independently predicted 5-year mortality when adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype. In sum, young adults with ischemic stroke have distinct demographic patterns and they frequently harbor traditional vascular risk factors. Etiology in the young is extremely diverse, but in as many as one-third the exact cause remains unknown. Silent brain infarcts and leukoaraiosis are not uncommon brain imaging findings in these patients and should not be overlooked due to their potential prognostic relevance. Outcomes in young adults with hemispheric ischemic stroke can safely be improved with intravenous thrombolysis. Furthermore, despite their overall low risk of death after ischemic stroke, several easily recognizable factors—of which most are modifiable—predict higher mortality in the long term in young adults.

Vibration characteristics and damage detection in a suspension bridge

Suspension bridges are flexible and vibration sensitive structures that exhibit complex and multi-modal vibration. Due to this, the usual vibration based methods could face a challenge when used for damage detection in these structures. This paper develops and applies a mode shape component specific damage index (DI) to detect and locate damage in a suspension bridge with pre-tensioned cables. This is important as suspension bridges are large structures and damage in them during their long service lives could easily go un-noticed. The capability of the proposed vibration based DI is demonstrated through its application to detect and locate single and multiple damages with varied locations and severity in the cables of the suspension bridge. The outcome of this research will enhance the safety and performance of these bridges which play an important role in the transport network.

The Palu Metamorphic Complex, NW Sulawesi, Indonesia: Origin and evolution of a young metamorphic terrane with links to Gondwana and Sundaland

The Palu Metamorphic Complex (PMC) is exposed in a late Cenozoic orogenic belt in NW Sulawesi, Indonesia. It is a composite terrane comprising a gneiss unit of Gondwana origin, a schist unit composed of meta-sediments deposited along the SE Sundaland margin in the Late Cretaceous and Early Tertiary, and one or more slivers of amphibolite with oceanic crust characteristics. The gneiss unit forms part of the West Sulawesi block underlying the northern and central sections of the Western Sulawesi Province. The presence of Late Triassic granitoids and recycled Proterozoic zircons in this unit combined with its isotopic signature suggests that the West Sulawesi block has its origin in the New Guinea margin from which it rifted in the late Mesozoic. It docked with Sundaland sometime during the Late Cretaceous. U–Th–Pb dating results for monazite suggest that another continental fragment may have collided with the Sundaland margin in the earliest Miocene. High-pressure (HP) and ultrahigh-pressure (UHP) rocks (granulite, peridotite, eclogite) are found as tectonic slices within the PMC, mostly along the Palu–Koro Fault Zone, a major strike-slip fault that cuts the complex. Mineralogical and textural features suggest that some of these rocks resided at depths of 60–120 km during a part of their histories. Thermochronological data (U–Th–Pb zircon and 40Ar/39Ar) from the metamorphic rocks indicate a latest Miocene to mid-Pliocene metamorphic event, which was accompanied by widespread granitoid magmatism and took place in an extensional tectonic setting. It caused recrystallization of, and new overgrowths on, pre-existing zircon crystals, and produced andalusite–cordierite–sillimanite–staurolite assemblages in pelitic protoliths, indicating HT–LP (Buchan-type) metamorphism. The PMC was exhumed as a core complex at moderate rates (c. 0.7–1.0 mm/yr) accompanied by rapid cooling in the Plio-Pleistocene. Some of the UHP rocks were transported to the surface at significantly higher rates (⩾16 mm/yr). The results of our study do not support recent plate tectonic reconstructions that propose a NW Australia margin origin for the West Sulawesi block (e.g. Hall et al., 2009).

Primer-independent initiation of RNA synthesis by SeMV recombinant RNA-dependent RNA polymerase

Sesbania mosaic virus (SeMV),a single-strand positive-sense RNA plant virus, belongs to the genus Sobemoviruses. Mechanism of replication in Sobemoviruses is poorly understood. In the present study, SeMV RNA-dependent RNA polymerase (RdRp) was overexpressed and purified as a thioredoxin-tagged protein. The recombinant SeMV RdRp could synthesize RNA from genomic or subgenomic RNA templates, even in the absence ofthe protein primer, VPg. Analysis of the product indicated that it was double-stranded and that the mode of initiation was de novo. Mutational analysis of the 3' UTR of subgenomic RNA revealed that a stem-loop structure at the 3' end was important. Further, analysis of this stem-loop showed that the SeMV RdRp was capable of recognizing stem-loop structures of various lengths and forms. These results demonstrate that the SeMV RdRp is capable of primer-independent RNAsynthesis in vitro. (C) 2010 Elsevier Inc. All rights reserved.

Main chain and segmental dynamics of semi interpenetrating based on polyisoprene and poly(methyl methacrylate)

Main chain and segmental dynamics of polyisoprene (PI) and poly(methyl methacrylate)(PMMA) chains in semi IPNs were systematically studied over a wide range of temperatures (above and below T-g of both polymers) as a function of composition, crosslink density, and molecular weight. The immiscible polymers retained most of its characteristic molecular motion; however, the semi IPN synthesis resulted in dramatic changes in the motional behavior of both polymers due to the molecular level interpenetration between two polymer chains. ESR spin probe method was found to be sensitive to the concentration changes of PMMA in semi IPNs. Low temperature spectra showed the characteristics of rigid limit spectra, and in the range of 293-373 K.complex spectra were obtained with the slow component mostly arisingout of the PMMA rich regions and fast component from the PI phase. We found that the rigid PMMA chains closely interpenetrated into thehighly mobile PI network imparts motional restriction in nearby PI chains, and the highly mobile PI chains induce some degree of flexibility in highly rigid PMMA chains. Molecular level interchain mixing was found to be more efficient at a PMMA concentration of 35 wt.%. Moreover, the strong interphase formed in the above mentionedsemi IPN contributed to the large slow component in the ESR spectra at higher temperature. The shape of the spectra along with the data obtained from the simulations of spectra was correlated to the morphology of the semi IPNs. The correlation time measurement detected the motional region associated with the glass transition of PI and PMMA, and these regions were found to follow the same pattern of shifts in a-relaxation of PI and PMMA observed in DMA analysis. Activation energies associated with the T-g regions were also calculated. T-50G was found to correlate with the T-g of PMMA, and the volume of polymer segments undergoing glass transitional motion was calculated to be 1.7 nm(3).C-13 T-1 rho measurements of PMMA carbons indicate that the molecular level interactions were strong in semi IPN irrespective of the immiscible nature of polymers. The motional characteristics of H atoms attached to carbon atoms in both polymers were analyzed using 2D WISE NMR. Main relaxations of both components shifted inward, and both SEM and TEM analysis showed the development of a nanometer sized morphology in the case of highly crosslinked semi IPN. (C) 2010 Elsevier Ltd. All rights reserved.

Observation of the Ωb- baryon and measurement of the properties of the Ξb- and Ωb- baryons

We report the observation of the bottom, doubly-strange baryon Omega^-_b through the decay chain Omega^-_b -> J/psi Omega^-, where J/psi -> mu^+ mu^-, Omega^- -> Lambda K^-, and Lambda -> p pi^-, using 4.2 fb^{-1} of data from p\bar p collisions at sqrt{s}=1.96 TeV, and recorded with the Collider Detector at Fermilab. A signal is observed whose probability of arising from a background fluctuation is 4.0 * 10^{-8}, or 5.5 Gaussian standard deviations. The Omega^-_b mass is measured to be 6054.4 +/- 6.8 (stat.) +/- 0.9 (syst.) MeV/c^2. The lifetime of the Omega^-_b baryon is measured to be 1.13^{+0.53}_{-0.40}(stat.) +/- 0.02(syst.)$ ps. In addition, for the \Xi^-_b baryon we measure a mass of 5790.9 +/- 2.6(stat.) +/- 0.8(syst.) MeV/c^2 and a lifetime of 1.56^{+0.27}_{-0.25}(stat.) +/-0.02(syst.) ps. Under the assumption that the \Xi_b^- and \Omega_b^- are produced with similar kinematic distributions to the \Lambda^0_b baryon, we find sigma(Xi_b^-) B(Xi_b^- -> J/psi Xi^-)}/ sigma(Lambda^0_b) B(Lambda^0_b -> J/psi Lambda)} = 0.167^{+0.037}_{-0.025}(stat.) +/-0.012(syst.) and sigma(Omega_b^-) B(Omega_b^- -> J/psi Omega^-)/ sigma(Lambda^0_b) B(Lambda^0_b -> J/psi Lambda)} = 0.045^{+0.017}_{-0.012}(stat.) +/- 0.004(syst.) for baryons produced with transverse momentum in the range of 6-20 GeV/c.

Microbially induced separation of quartz from hematite using sulfate reducing bacteria

Cells and metabolic products of Desulfovibrio desulfuricans were successfully used to separate quartz from hematite through environmentally benign microbially induced flotation. Bacterial metabolic products such as extracellular proteins and polysaccharides were isolated from both unadapted and mineral-adapted bacterial metabolite and their basic characteristics were studied in order to get insight into the changes brought about on bioreagents during adaptation. Interaction between bacterial cells and metabolites with minerals like hematite and quartz brought about significant surface-chemical changes on both the minerals. Quartz was rendered more hydrophobic, while hematite became more hydrophilic after biotreatment.The predominance of bacterial polysaccharides on interacted hematite and of proteins on quartz was responsible for the above surface-chemical changes, as attested through adsorption studies. Surface-chemical changes were also observed on bacterial cells after adaptation to the above minerals. Selective separation of quartz from hematite was achieved through interaction with quartz-adapted bacterial cells and metabolite. Mineral-specific proteins secreted by quartz-adapted cells were responsible for conferment of hydrophobicity on quartz resulting in enhanced separation from hematite through flotation. (C) 2010 Elsevier B.V. All rights reserved.

An electron diffraction investigation of the molecular structure of trichloroacetonitrile

The molecular structure of trichloroacetonitrile has been studied by electron diffraction by the visual interpretation of sectored photographs. These parameters were obtained: C-N = 1.165 ± 0.025, C-C = 1.465 ± 0.025, C-Cl = 1.765 ± 0.01 A., and < CCCl = 109.5 ± 1°.

Crystallographic Evolution, Dielectric, and Piezoelectric Properties of Bi4Ti3O12:W/Cr Ceramics

W/Cr codoped Bi4Ti3O12 ceramics, Bi4Ti3-xWxO12+x+0.2 wt%Cr2O3 (BITWC, x=0-0.15), were prepared using a solid-state reaction method. The crystallographic evolution and phase analysis were distinctly determined focusing on the X-ray diffraction peak changes in (020)/(200) and (220)/(1115) diffraction planes, by which the lattice parameters, a, b, and c can be refined. The thermal variations of permittivity, dielectric loss (tan delta), impedance, and electrical conductivity properties were characterized. A decrease in the values of Curie temperature from 675 degrees to 640 degrees C and an increase in the values of the dielectric constant due to an increase of W6+/Cr3+ content were observed. The highest piezoelectric constant, d(33) of 22 pC/N, was achieved with the composition of Bi4Ti2.975W0.025O12.025+0.2 wt% Cr2O3. Also, this composition had a lower electrical conductivity than the other investigated compositions.

On superconducting Y-Ba-Cu-O films prepared by printing on lumina substrates

This Letter attempts to examine the impact of the chemical interaction of the alumina substrate on the Y-Ba-Cu-O film deposited on it.

Search for new transparent conductors: Effect of Ge doping on the conductivity of Ga2O3, In2O3 and Ga1.4In0.6O3

Only a small amount (<= 3.5 mol%) of Ge can be doped in Ga2O3, Ga1.4In0.6O3 and In2O3 by means of solid state reactions at 1400 degrees C. All these samples are optically transparent in the visible range, but Ge-doped Ga2O3 and Ga1.4In0.6O3 are insulating. Only Ge-doped In2O3 exhibits a significant decrease in resistivity, the resistivity decreasing further on thermal quenching and H-2 reduction.The resistivity of 2.7% Ge-doped In2O3 after H-2 reduction shows a metallic behavior, and a resistivity of similar to 1 m Omega cm at room temperature, comparable to that of Sn-doped In2O3. (C) 2010 Elsevier Ltd. All rights reserved.

Hormones andCuscuta development: interaction of cytokinin and indole-3-acetic acid in the growth and curvature of subapical stem segments

Cuscuta stem (vines) exhibits two modes of growth—longitudinal elongation forming free-hanging vines, or coiling growth to twine around the host. The elongation zone of free-hanging vine extended up to 160 mm from the stem apex and in vivo growth rate (during 8 h of growth) was maximal in the 20-to-40-mm region. While gibberellic acid (GA3) or fusicoccin (FC) could maintain (GA3) or enhance (FC) the growth rate of apical (10 or 25 mm) segments, indole-3-acetic acid (IAA) (10 mgrM) induced growth only in subapical (5–160 mm) segments. In vitro growth rate induced by IAA (10 mgrM) was similar to the in vivo growth rate up to 40 mm. Thereafter, up to 100 mm, IAA induced growth rate exceeded in vivo growth. p ]Subapical segments (sim13 mm) from 5- to 40-mm regions responded to a cytokinin (BA, Z, or iP) or to low IAA (0.1 mgrM) with curved growth, whereas the segments grew straight in the presence of high IAA (10 mgrM). Curvature (measured as the angle subtended at the center of the circle of which the segment formed an arc) induced by BA and low (0.1 mgrM) IAA was greater than either added separately. Besides, segments induced to curve in BA + low-IAA solution could be made to straighten out by transferring to a solution containing high IAA (10 mgrM) with or without BA. Thus in vivo patterns of straight and coiling growth could be mimicked reversibly in vitro by adjusting the relative concentrations of cytokinin and auxin; low auxin and cytokinin induced coiling growth, whereas high auxin and cytokinin induced straight growth. p ]Beyond 40 mm, BA had no growth-promoting or curvative-inducing effect.Cuscuta vine segments thus showed sequential sensitivity to applied hormones, the apical region (0–25 mm) to GA3, the subapical (5–40 mm) region to BA and IAA and the region beyond (40–160 mm) to IAA alone.

A lock-type cell for NMR studies at high hydrostatic pressures and low temperatures

Details of a simple and convenient high-pressure cell for continuous-wave, wide-line nuclear magnetic resonance investigation at high pressures and low temperatures are described. Experimental results obtained with the cell at 14*108 Pa and 77K for ammonium iodide are presented briefly.

Improved growth of GaN layers on ultra thin silicon nitride/Si (111) by RF-MBE

High-quality GaN epilayers were grown on Si (1 1 1) substrates by molecular beam epitaxy using a new growth process sequence which involved a substrate nitridation at low temperatures, annealing at high temperatures, followed by nitridation at high temperatures, deposition of a low-temperature buffer layer, and a high-temperature overgrowth. The material quality of the GaN films was also investigated as a function of nitridation time and temperature. Crystallinity and surface roughness of GaN was found to improve when the Si substrate was treated under the new growth process sequence. Micro-Raman and photoluminescence (PL) measurement results indicate that the GaN film grown by the new process sequence has less tensile stress and optically good. The surface and interface structures of an ultra thin silicon nitride film grown on the Si surface are investigated by core-level photoelectron spectroscopy and it clearly indicates that the quality of silicon nitride notably affects the properties of GaN growth. (C) 2010 Elsevier Ltd. All rights reserved.