Nonlinear wave transmission and pressure on the fixed truncated breakwater using NURBS numerical wave tank

Fully nonlinear wave interaction with a fixed breakwater is investigated in a numerical wave tank (NWT). The potential theory and high-order boundary element method are used to solve the boundary value problem. Time domain simulation by a mixed Eulerian-Lagrangian (MEL) formulation and high-order boundary integral method based on non uniform rational B-spline (NURBS) formulation is employed to solve the equations. At each time step, Laplace equation is solved in Eulerian frame and fully non-linear free-surface conditions are updated in Lagrangian manner through material node approach and fourth order Runge-Kutta time integration scheme. Incident wave is fed by specifying the normal flux of appropriate wave potential on the fixed inflow boundary. To ensure the open water condition and to reduce the reflected wave energy into the computational domain, two damping zones are provided on both ends of the numerical wave tank. The convergence and stability of the presented numerical procedure are examined and compared with the analytical solutions. Wave reflection and transmission of nonlinear waves with different steepness are investigated. Also, the calculation of wave load on the breakwater is evaluated by first and second order time derivatives of the potential

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Transcultural adaptation and testing of psychometric properties of the Korean version of the Hip Disability and Osteoarthritis Outcome Score (HOOS)

SummaryObjectiveTranslation and transcultural adaptation of the Hip Disability and Osteoarthritis Outcome Score (HOOS LK 2.0) into Korean language was performed, followed by test of psychometric properties.DesignA Korean version of the HOOS was produced according to internationally recommended guidelines, which included forward translation, reconciliation, back translation, harmonization, cognitive debriefing and proof reading. The psychometric properties including reliability and validity were evaluated. The reliability, including the internal consistency and test–retest reliability, was then evaluated in a hip osteoarthritis population (OA group, n=75). The validity, including the convergent validity was assessed comparing HOOS with the Short Form-36 (SF-36) and pain on a visual analogue scale (VAS) scale. Responsiveness was evaluated in a population scheduled for total hip arthroplasty (THA group, n=35).ResultsAll subscales of the HOOS showed satisfactory internal consistency (Cronbach’s alpha>0.7) without floor and ceiling effects. Intraclass correlation coefficient (ICC) spanned from 0.78 to 0.93. In terms of convergent validity, Activity of Daily Living (ADL) subscale showed the strongest correlations with Physical Function (PF) (r=0.801) and Bodily Pain (BP) (r=0.810) in the subscales of SF-36. For responsiveness, all HOOS subscale scores improved significantly (P<0.05) postoperatively.ConclusionsThe Korean version of HOOS showed satisfactory internal consistency, test–retest reliability, convergent validity, and responsiveness. This study shows that the HOOS questionnaire developed in West is, with transcultural adaptation, relevant for use among patients in East Asia

Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells

Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. In contrast, nontumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death, and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur.Breast Cancer NowWalk the WalkAlzheimer's Research UKDepto. de Biología CelularFac. de Ciencias BiológicasTRUEpu

Systematic analysis snake neurotoxins' functional classification using a data warehousing approach

10.1093/bioinformatics/bth430Bioinformatics20183466-3480BOIN

miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness

Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy

Discovering network topology in the presence of Byzantine faults

Abstract. We study the problem of Byzantine-robust topology discovery in an arbitrary asynchronous network. We formally state the weak and strong versions of the problem. The weak version requires that either each node discovers the topology of the network or at least one node detects the presence of a faulty node. The strong version requires that each node discovers the topology regardless of faults. We focus on non-cryptographic solutions to these problems. We explore their bounds. We prove that the weak topology discovery problem is solvable only if the connectivity of the network exceeds the number of faults in the system. Similarly, we show that the strong version of the problem is solvable only if the network connectivity is more than twice the number of faults. We present solutions to both versions of the problem. Our solutions match the established graph connectivity bounds. The programs are terminating, they do not require the individual nodes to know either the diameter or the size of the network. The message complexity of both programs is low polynomial with respect to the network size.