In this paper, we utilize prioritized aggregation operators to develop some single-valued neutrosophic Dombi prioritized aggregation operators: single-valued neutrosophic Dombi prioritized average ...(SVNDPA) operator, single-valued neutrosophic Dombi rioritized geometric (SVNDPG) operator, single-valued neutrosophic Dombi prioritized weighted average (SVNDPWA) operator and single-valued neutrosophic Dombi prioritized weighted geometric (SVNDPWG) operator. The prominent characteristic of these proposed operators are studied. Then, we have utilized the SVNDPWA and SVNDPWG operators to develop some approaches to solve the single-valued neutrosophic multiple attribute decision making problems. Finally, a practical example about talent introduction is given to verify the developed approach and to demonstrate its practicality and effectiveness.
In this paper, we investigate the multiple attribute decision making (MADM) problems with 2-tuple intuitionistic fuzzy linguistic information. Then, we utilize arithmetic and geometric operations to ...develop some 2-tuple intuitionistic fuzzy linguistic aggregation operators. The prominent characteristic of these proposed operators are studied. Then, we have utilized these operators to develop some approaches to solve the 2-tuple intuitionistic fuzzy linguistic MADM problems. Finally, a practical example for enterprise resource planning (ERP) system selection is given to verify the developed approach and to demonstrate its practicality and effectiveness.
Abstract Background Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease ...(ATH), adherence is poor. Objectives The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients. Methods We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files. Results Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio HR: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups. Conclusions Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events.
Increasing evidence indicates that long noncoding RNAs (lncRNAs) have important roles in various physiological processes and dysfunction of lncRNAs could be a prevalent cause in human diseases. Here ...we functionally characterized the nuclear-enriched lncRNA SNHG1, which is highly expressed in multiple types of cancer. We also provide evidence that SNHG1 promotes cancer cell growth by regulating gene expression both in cis and in trans. SNHG1 was involved in the AKT signaling pathway as it promotes the neighboring transcription of the protein-coding gene SLC3A2 in cis by binding the Mediator complex to facilitate the establishment of enhancer-promoter interaction. In trans, SNHG1 directly interacted with central domain of FUBP1 and antagonize the binding of FBP-interacting repressor to FUBP1, thereby coordinating the expression of the oncogene MYC. Collectively, our findings demonstrate that lncRNA SNHG1 can function both in cis and in trans with distinct mechanisms to regulate transcription, promoting tumorigenesis and cancer progression.
The change in the hydrogen-trapping behavior of a TiC particle accompanying its coherent to incoherent interfacial-character transition in a 0.05C-0.20Ti-2.0Ni steel that was quenched and tempered in ...a partially protective argon atmosphere and in ultrahigh vacuum (UHV) has been studied by thermal desorption spectrometry (TDS). The results indicated that (semi)coherent TiC precipitates demonstrate distinctly different hydrogen-trapping features from that of incoherent TiC particles with respect to hydrogen capacity, interaction energy with hydrogen, locations available for hydrogen occupation, and the capability of hydrogen absorption from the environment. The broad (semi)coherent interface of the disc-shaped (semi)coherent TiC precipitate does not trap hydrogen during tempering in a partially protected argon atmosphere, but traps hydrogen during cathodic charging at room temperature. The semicoherent interface traps 1.3 atoms/nm^sup 2^ of hydrogen at the core of the misfit dislocation with short-time charging (1 hour), which is characterized by a desorption activation energy of 55.8 kJ/mol. The side interface of the (semi)coherent TiC precipitate acts like the broad interface when the precipitate is small. As the precipitate grows, the side interface gradually loses its coherency and results in a simultaneous increase in the trapping activation energy and the binding energy. An increase in the trapping activation energy, i.e., the energy barrier for trapping, makes hydrogen trapping more difficult in cathodic charging at room temperature, while an increase in the binding energy enhances the capability of hydrogen absorption from the atmosphere during heat treatment. An incoherent TiC particle is not able to trap hydrogen during cathodic charging at room temperature due to its high energy barrier for trapping, but absorbs hydrogen during heat treatment at high temperatures. The amount of hydrogen that is trapped by incoherent TiC particles depends on their volume, which strongly indicates that incoherent TiC particles trap hydrogen within them rather than at the particle/matrix interface. Octahedral carbon vacancies are supposedly the hydrogen trap sites in incoherent TiC particles. PUBLICATION ABSTRACT
This paper introduces a novel high order interface scheme, the matched interface and boundary (MIB) method, for solving elliptic equations with discontinuous coefficients and singular sources on ...Cartesian grids. By appropriate use of auxiliary line and/or fictitious points, physical jump conditions are enforced at the interface. Unlike other existing interface schemes, the proposed method disassociates the enforcement of physical jump conditions from the discretization of the differential equation under study. To construct higher order interface schemes, the proposed MIB method bypasses the major challenge of implementing high order jump conditions by repeatedly enforcing the lowest order jump conditions. The proposed MIB method is of arbitrarily high order, in principle. In treating straight, regular interfaces we construct MIB schemes up to 16th-order. For more general elliptic problems with curved, irregular interfaces and boundary, up to 6th-order MIB schemes have been demonstrated. By employing the standard high-order finite difference schemes to discretize the Laplacian, the present MIB method automatically reduces to the standard central difference scheme when the interface is absent. The immersed interface method (IIM) is regenerated for a comparison study of the proposed method. The robustness of the MIB method is verified against the large magnitude of the jump discontinuity across the interface. The nature of high efficiency and low memory requirement of the MIB method is extensively validated via solving various elliptic immersed interface problems in two- and three-dimensions.
Low strain hardening has hitherto been considered an intrinsic behavior for most nanocrystalline (NC) metals, due to their perceived inability to accumulate dislocations. In this Letter, we show ...strong strain hardening in NC nickel with a grain size of approximately 20 nm under large plastic strains. Contrary to common belief, we have observed significant dislocation accumulation in the grain interior. This is enabled primarily by Lomer-Cottrell locks, which pin the lock-forming dislocations and obstruct dislocation motion. These observations may help with developing strong and ductile NC metals and alloys.
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy for which new therapeutic approaches are required. One such potential therapeutic strategy is to target the ubiquitin-like ...modifier-activating enzyme 1 (UBA1), the initiating enzyme in the ubiquitylation cascade in which proteins are tagged with ubiquitin moieties to regulate their degradation or function. Here, we evaluated TAK-243, a first-in-class UBA1 inhibitor, in preclinical models of AML. In AML cell lines and primary AML samples, TAK-243 induced cell death and inhibited clonogenic growth. In contrast, normal hematopoietic progenitor cells were more resistant. TAK-243 preferentially bound to UBA1 over the related E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 decreased levels of ubiquitylated proteins, increased markers of proteotoxic stress and DNA damage stress. In vivo, TAK-243 reduced leukemic burden and targeted leukemic stem cells without evidence of toxicity. Finally, we selected populations of AML cells resistant to TAK-243 and identified missense mutations in the adenylation domain of UBA1. Thus, our data demonstrate that TAK-243 targets AML cells and stem cells and support a clinical trial of TAK-243 in this patient population. Moreover, we provide insight into potential mechanisms of acquired resistance to UBA1 inhibitors.
This paper presents a differential geometry based model for the analysis and computation of the equilibrium property of solvation. Differential geometry theory of surfaces is utilized to define and ...construct smooth interfaces with good stability and differentiability for use in characterizing the solvent–solute boundaries and in generating continuous dielectric functions across the computational domain. A total free energy functional is constructed to couple polar and nonpolar contributions to the solvation process. Geometric measure theory is employed to rigorously convert a Lagrangian formulation of the surface energy into an Eulerian formulation so as to bring all energy terms into an equal footing. By optimizing the total free energy functional, we derive coupled generalized Poisson–Boltzmann equation (GPBE) and generalized geometric flow equation (GGFE) for the electrostatic potential and the construction of realistic solvent–solute boundaries, respectively. By solving the coupled GPBE and GGFE, we obtain the electrostatic potential, the solvent–solute boundary profile, and the smooth dielectric function, and thereby improve the accuracy and stability of implicit solvation calculations. We also design efficient second-order numerical schemes for the solution of the GPBE and GGFE. Matrix resulted from the discretization of the GPBE is accelerated with appropriate preconditioners. An alternative direct implicit (ADI) scheme is designed to improve the stability of solving the GGFE. Two iterative approaches are designed to solve the coupled system of nonlinear partial differential equations. Extensive numerical experiments are designed to validate the present theoretical model, test computational methods, and optimize numerical algorithms. Example solvation analysis of both small compounds and proteins are carried out to further demonstrate the accuracy, stability, efficiency and robustness of the present new model and numerical approaches. Comparison is given to both experimental and theoretical results in the literature.
This paper introduces a series of novel hierarchical implicit derivative matching methods to restore the accuracy of high-order finite-difference time-domain (FDTD) schemes of computational ...electromagnetics (CEM) with material interfaces in one (1D) and two spatial dimensions (2D). By making use of fictitious points, systematic approaches are proposed to locally enforce the physical jump conditions at material interfaces in a preprocessing stage, to arbitrarily high orders of accuracy in principle. While often limited by numerical instability, orders up to 16 and 12 are achieved, respectively, in 1D and 2D. Detailed stability analyses are presented for the present approach to examine the upper limit in constructing embedded FDTD methods. As natural generalizations of the high-order FDTD schemes, the proposed derivative matching methods automatically reduce to the standard FDTD schemes when the material interfaces are absent. An interesting feature of the present approach is that it encompasses a variety of schemes of different orders in a single code. Another feature of the present approach is that it can be robustly implemented with other high accuracy time-domain approaches, such as the multiresolution time-domain method and the local spectral time-domain method, to cope with material interfaces. Numerical experiments on both 1D and 2D problems are carried out to test the convergence, examine the stability, access the efficiency, and explore the limitation of the proposed methods. It is found that operating at their best capacity, the proposed high-order schemes could be over 2000 times more efficient than their fourth-order versions in 2D. In conclusion, the present work indicates that the proposed hierarchical derivative matching methods might lead to practical high-order schemes for numerical solution of time-domain Maxwell's equations with material interfaces.
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