PML Regions Research Articles

A unified higher-order unsplit CFS-PML technique for solving second-order seismic equations using discontinuous Galerkin method

The absorbing boundary conditions play a key role in numerical simulations. The complex frequency-shifted perfectly matched layer (CFS-PML), one of the absorbing boundary conditions, has attracted widespread attention because it can efficiently attenuate near-grazing incident waves and evanescent waves. In practical application, the distinct boundary reflections still exist using the CFS-PML in a thin PML region. To further enhance the absorbing performance, we have developed a novel unified high-order unsplit CFS-PML technique. The high-order CFS-PML combined with the discontinuous Galerkin (DG) method is applied to solve the second-order seismic wave equation on an unstructured mesh. In this work, we establish a unified framework for high-order unsplit CFS-PML formulations. The classical CFS-PML is the first-order form of our proposed unsplit high-order approach. By using auxiliary variables and auxiliary ordinary differential equations (AODEs), a higher-order CFS-PML formulation can be reduced to a first-order CFS-PML formula. For an Nth-order AODE CFS-PML, it will lead to (2N-1) additional variables and (2N-1) auxiliary differential equations. Taking second- and third-order as examples, we have derived the high-order unsplit AODE CFS-PML expressions in detail. The DG method can effectively deal with complex geological structures, such as caves, cracks, faults, etc., which yields more accurate numerical solutions. We incorporate the high-order unsplit AODE CFS-PML technique into the DG method to approximate seismic wave equations. Their strengths are combined to calculate the propagating wavefield in more complex finite models and obtain better results. In addition, the stability conditions of the second- and third-order CFS-PMLs are provided. We perform the high-order unsplit CFS-PML implementation for seismic wave modeling in several models. The isotropic and anisotropic examples prove that the high-order unsplit CFS-PML enjoys better absorbing performance than the classical CFS-PML. The numerical result for the graben model certifies the feasibility and flexibility of our proposed high-order CFS-PML combined with the DG method.

81. Discrepancies in the detection of PML::RARA gene rearrangement by FISH using commonly used dual-color dual-fusion probes

Acute promyelocytic leukemia (APL) is a medical emergency with serious complications (e.g., DIC), requires prompt treatment and rapid test turnaround time (TAT) for diagnosis confirmation. APL results from a fusion of the PML gene (15q24) with the RARA gene (17q21) creating a fusion gene on the derivative chromosome 15. There are multiple breakpoints that can occur. PML::RARA is the most common (98%) rearrangement. Fluorescent in situ Hybridization (FISH) study helps in the diagnosis of APL with rapid TAT. PML::RARA dcdf FISH probes from either Abbott Molecular or Cytocell are commonly used in the Cytogenetics laboratories. Although they both detect PML::RARA gene rearrangements they differ in their probe design, resulting in the limitation of breakpoint coverage in atypical PML-RARA insertion rearrangements. Our lab has identified two unique cases of APL which were tested at diagnosis using PML::RARA FISH probe set. Both cases showed an atypical rearrangement with single fusion signal. First case was positive by Abbott probe and negative by Cytocell, metaphase FISH confirmed insertion of PML region near RARA on Chromosome 17. Other case was positive by Cytocell and negative by Abbott, metaphase FISH confirmed insertion of RARA region near PML on chromosome 15. Both cases were positive for PML::RARA transcript presence by qRT-PCR. This data suggests potential limitation of widely used PML::RARA FISH probes from different FISH probe vendors. In cases with high suspicion of APL with a negative FISH result, reflex FISH test using probes having coverage different from initial tested probe and molecular PCR

Unsplit-field higher-order nearly PML for arbitrary media in EM simulation

An unsplit-field higher order nearly perfectly matched layer (NPML) based on the auxiliary differential equation approach is introduced in three-dimensional finite-difference time-domain lattices. The proposed scheme has the advantage of both the NPML scheme and the higher order concept in terms of the improved absorbing performance and considerable computational efficiency. By incorporating with the generalized material independent concept, the proposed implementation is independent of the material's type. Thus, it has the advantages of terminating arbitrary media without changing the updated equations in the PML regions. Its effectiveness and efficiency is further demonstrated through numerical examples.

PML absorbing boundary condition for structure-preserving seismic wave modeling

Some efficient structure preserving algorithms have been proposed for high precision seismic exploration and detection in recent years. However, feasible artificial boundary conditions to truncate unbounded medium are never discussed in structure preserving seismic modeling. We pay our emphasis on application of perfectly matched layer absorbing boundary condition (PML ABC) to fit the structure preserving algorithms. In the domain of interest, a typical structure preserving algorithm is presented to discretize the conservative dynamic system, while in the PML region, traditional central difference is applied to solve the dissipative system. In the adjacent region of the interior and exterior domains, the temporary values of wave field between two time steps are approximated by interpolation using the present and the updated value of the wave fields in the PML region. A numerical experiment is adopted to demonstrate compatibility of the algorithms and no visible reflections of outgoing waves occur on the edge of interior domain.

Different implementations of material independent multi‐order nearly perfectly matched layers for EM simulations

AbstractTo deal with EM simulations with the low‐frequency evanescent and propagation waves, multi‐order nearly perfectly matched layers (NPML) with complex frequency shifted factor are presented to terminate finite‐difference time‐domain (FDTD) domains. By incorporating the digital signal processing techniques including the bilinear Z‐transform, matched Z‐transform, and direct Z‐transform methods, the proposals can not only obtain better performance compared with the original NPMLs but also have considerable efficiency compared with other multi‐order PMLs. Meanwhile, these implementations can terminate arbitrary mediums without changing the field‐updated equations in the PML regions. Based upon the multi‐order concept, the proposals can be switched flexibly between the first order and multi‐order according to different EM simulations by changing the optimized parameters. Numerical results indicate that our proposals can not only enjoy higher computational efficiency but also easier to implement according to different mediums in the EM modeling and simulations.

Efficient Implementations of SC-PML for Arbitrary Media Using DSP Techniques

Through the digital signal processing (DSP) techniques, two simple implementations of the stretched coordinate perfectly matched layer (SC-PML) are proposed in this letter. Specially, they are based on the bilinear Z-transform and matched Z-transform methods, respectively. In addition, incorporating the concept of generalized material independent PML into these formulations enable them to be completely independent of material properties. Thus, these new implementations can be used to terminate the finite-difference time-domain lattices composed of arbitrary media. As for resource utilization, the proposals can guarantee that only one auxiliary variable is needed for each field component in the whole PML regions. A brief comparison of the number of floating-point operations and constant coefficients successfully shows that they can achieve a bit higher efficiency compared with other published efficient SC-PML implementations. Finally, two numerical examples of electromagnetic waves radiating in vacuum and soil half-space are provided to validate these DSP-based algorithms.

Specific evaluation of tunnel lining multi-defects by all-refined GPR simulation method using hybrid algorithm of FETD and FDTD

Irregular and complicated tunnel lining defects cannot be finely depicted with the standard finite difference simulation method based on regular mesh due to its irregular geometrical characteristics and complex physical properties of various defects. To solve this problem, a new hybrid algorithm is proposed for all-refined ground penetrating radar (GPR) simulation by combining the finite element time domain (FETD) and finite difference time domain (FDTD), which employs FETD algorithm in main region based on unstructured Delaunay mesh and Newmark-β implicit FDTD algorithm in PML region based on convolutional perfectly matched layer (CPML), respectively. The calculation efficiency and simulation accuracy of different algorithms methods are compared in detail using a representative numerical model with a water-filled void embedded. In addition, several complicated numerical models involving different typical defects and mixed case (e.g. non-compactness, voids, leaking with fractured and cracks, etc.) are also conducted, the results presented show that the proposed hybrid algorithm helps GPR practitioners to gain a deeper insight into the effects of multi-defects on the propagation characteristic of electromagnetic wave, and provides more precise technical guidance for defect interpretation. Moreover, spectrum analysis of echoes responses from defects, by using the short-time Fourier transform (STFT), is also presented, including amplitude spectrum, frequency spectrum and mode of dominant frequency.

Complex-Frequency Shifted PML Formulation for the 3-D MNL-FDTD Method

This letter presents a complex-frequency shifted perfectly matched layer (CFS-PML) formulation for the partially implicit Magnetically-mixed Newmark-Leapfrog finite-difference time-domain (MNL-FDTD) method. Its formulation is based on time-dependent Maxwell's equations in CFS-PML media and the auxiliary differential equation (ADE) of PML auxiliary variables. In the PML region, the efficiency of auxiliary variable terms of the formulated scheme is same as that of Roden's convolutional PML for Yee's FDTD. It is demonstrated that reflection error of MNL-FDTD with CFS-PML is comparable to those of the conventional explicit and implicit FDTDs with CFS-PML.

<i>Z</i>-Transform Implementation of the CFS-PML for Truncating 3D Meta-Material FDTD Domains

Efficient Z-transform implementa-tion of the complex frequency-shifted perfectly matched layer (CFS-PML) based on the stretched coordinate PML (SC-PML) formulations and the D-B formulations is proposed for truncating meta-material finite-difference time-domain (FDTD) lattices. In the proposed PML formulations, the Z-transform method is incorporated into the CFS-PML FDTD implementation. The main advantage of the proposed formulations can allow direct FDTD implementation of the Maxwell’s equations in the PML regions. A numerical test has been carried out in a three dimensions (3-D) FDTD domain to validate the proposed formulations. It is shown that the proposed formulations with CFS scheme are efficient in holding good absorbing performances.

Time harmonic analysis of dam-foundation systems by perfectly matched layers

Perfectly matched layers are employed in time harmonic analysis of dam-foundation systems. The Lysmer boundary condition at the truncation boundary of the PML region has been incorporated in the formulation of the dam-foundation FE model (including PML). The PML medium is defined in a way that the formulation of the system can be transformed into time domain. Numerical experiments show that applying Lysmer boundary conditions at the truncation boundary of the PML area reduces the computational cost and make the PML approach a more efficient technique for the analysis of dam-foundation systems.

Application of perfectly matched layers in the transient analysis of dam–reservoir systems

The transient analysis of dam–reservoir systems by employing perfectly matched layers has been investigated. In previous studies, boundary conditions of the PML region in the reservoir have been neglected. In this paper, they are incorporated completely in the formulation. Moreover, a technique is introduced to involve the effect of incident waves caused by vertical ground motions at the reservoir bottom in the analysis. Performing several numerical experiments indicates that applying boundary conditions of the PML domain and utilizing the proposed method for vertical excitation cases reduce the computational cost significantly and make the PML method a very efficient approach for the transient analysis of dam–reservoir systems.

Dual roles for lysine 490 of promyelocytic leukemia protein in the transactivation of glucocorticoid receptor-interacting protein 1

Glucocorticoid receptor-interacting protein 1 (GRIP1), a p160 family nuclear receptor co-activator protein, has three activation domains that recruit at least three secondary co-activators: CBP/p300, co-activator-associated arginine methyltransferase 1, and coiled-coil co-activator, which exhibits histone acetyltransferase and/or arginine methyltransferase activities. The regulatory mechanisms underlying the co-activation functions of GRIP1, which associates with promyelocytic leukemia protein (PML) in PML-nuclear bodies, are not well-understood. This study showed that PML specifically and dramatically enhanced the C-terminal transactivation activity of GRIP1 by directly binding to GRIP1 but only when it was sumoylated. Most of the transactivation activity resided in the N-terminal PML regions that are conserved among isoforms. Three N-terminal sumoylation residues (Lys 65, 160, and 490) exhibited differential roles in the regulation of GRIP1 activity, and the sumoylation of Lys 490 acted as the primary nuclear localization signal of PML. While GRIP1 transactivation was stimulated to a similar degree by PML (K490R), located in the nucleus, and wild-type PML, PML (K490D) and the C-truncated mutant PML1–489 both displayed an epinuclear localization and were mostly inactive in stimulating GRIP. Based on these data, nuclear foci, nuclear localization, and the sumoylation status of Lys 490 were not essential for the enhancement of GRIP1 activity by PML, but the charge status of Lys 490 was important for subcellular localization of PML and cross-talk between its N- and C-terminal regions to modulate transcriptional activation. Taken together, these results provide insight into the regulatory mechanisms of PML that control the functional activities of GRIP1.

Discretization of the CFS‐PML for computational electromagnetics using discrete differential forms

AbstractA new numerical discretization of the complex frequency shifted‐perfectly matched layer (CFS‐PML) is presented for truncation of open domains. This discretization is based on the theory of discrete differential forms applied to electromagnetism, which guarantees both the simplification of the algorithms and a more elegant formulation of expression. The curl Maxwell's equations are solved in time domain in terms of electric e magnetic fields. The Ampere‐Maxwell law with, the constitutive relations included through the Hodge operator, is discretized in space by applying the Galerkin method. Conversely, the Faraday law is represented by topological relations via incidence matrix. The time domain discretization uses the leap‐frog scheme with a recursive convolution inside PML region. Two examples are shown, the first one to validate the CFS‐PML procedure and the second one to solve a typical ground penetrating radar scenario which include a lossy media. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:351–357, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27298

Requirement of PML SUMO Interacting Motif for RNF4- or Arsenic Trioxide-Induced Degradation of Nuclear PML Isoforms

PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene. This variability is important for the function of the different PML isoforms. PML NB formation requires the covalent linkage of SUMO to PML. Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Furthermore, the presence of a bona fide SUMO Interacting Motif (SIM) within the C-terminal region of PML seems to be required for recruitment of other SUMOylated proteins within PML NBs. This motif is present in all PML isoforms, except in the nuclear PMLVI and in the cytoplasmic PMLVII. Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As2O3 enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI). In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As2O3-induced PML degradation. Similarly, mutation of the SIM in PMLIII abrogated its sensitivity to As2O3-induced degradation. PMLVI and PMLIII-SIM mutant still interacted with RNF4. However, their resistance to the degradation process was due to their inability to be polyubiquitinated and to recruit efficiently the 20S core and the β regulatory subunit of the 11S complex of the proteasome in PML NBs. Such resistance of PMLVI to As2O3-induced degradation was alleviated by overexpression of RNF4. Our results demonstrate that the SIM of PML is dispensable for PML SUMOylation and interaction with RNF4 but is required for efficient PML ubiquitination, recruitment of proteasome components within NBs and proteasome-dependent degradation of PML in response to As2O3.

Efficient LOD-SC-PML Formulations for Electromagnetic Fields in Dispersive Media

Efficient locally one dimensional stretched-coordinate perfectly matched layer (LOD-SC-PML) formulations are presented for truncating open region dispersive finite difference time domain (FDTD) applications. The field equations in the PML regions are implemented with the minimal additional auxiliary variables that will be computed only in one of the LOD-FDTD scheme stages. It has been shown that the proposed formulations are computationally efficient more than the alternating direction implicit SC-PML counterpart, while maintaining approximately the same numerical performance.

Analysis of t(15;17) chromosomal breakpoint sequences in therapy‐related versus de novo acute promyelocytic leukemia: Association of DNA breaks with specific DNA motifs at PML and RARA loci

We compared genomic breakpoints at the PML and RARA loci in 23 patients with therapy-related acute promyelocytic leukemia (t-APL) and 25 de novo APL cases.Eighteen of 23 t-APL cases received the topoisomerase II poison mitoxantrone for their primary disorder. DNA breaks were clustered in a previously reported 8 bp "hot spot" region of PML corresponding to a preferred site of mitoxantrone-induced DNA topoisomerase II-mediated cleavage in 39% of t-APL occurring in patients exposed to this agent and in none of the cases arising de novo (P = 0.007). As to RARA breakpoints, clustering in a 3' region of intron 2 (region B) was found in 65% of t-APL and 28% of de novo APL patients, respectively. Scan statistics revealed significant clustering of RARA breakpoints in region B in t-APL cases (P = 0.001) as compared to de novo APL (P = 1). Furthermore, approximately 300 bp downstream of RARA region B contained a sequence highly homologous to a topoisomerase II consensus sequence. Biased distribution of DNA breakpoints at both PML and RARA loci suggest the existence of different pathogenetic mechanisms in t-APL as compared with de novo APL.

PML-RARα/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia

Many different molecular mechanisms have been associated with PML-RARalpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARalpha binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RARalpha with RXR to the vast majority of these binding regions. Genome-wide epigenetic studies revealed that treatment with pharmacological doses of all-trans retinoic acid induces changes in H3 acetylation, but not H3K27me3, H3K9me3, or DNA methylation at the PML-RARalpha/RXR binding sites or at nearby target genes. Our results suggest that PML-RARalpha/RXR functions as a local chromatin modulator and that specific recruitment of histone deacetylase activities to genes important for hematopoietic differentiation, RAR signaling, and epigenetic control is crucial to its transforming potential.

Double Genetic Mutations in PML-Rara Fusion Gene Confirmed in a Patient Showing Resistance to All-Trans Retinoic Acid and Arsenic-Trioxide Therapy.

Abstract 1743Poster Board I-769 BackgroundMolecular targeting drugs, all-trans retinoic acid (ATRA)and arsenic trioxide (ATO), have major advances in the treatment of acute promyelocytic leukemia (APL). However, resistance to these drugs has been also observed in clinical practice. ATRA acts as a ligand for retinoic acid receptor alpha (RAR) and restores the aberrant transcription repression by PML-RARA fusion protein in APL cells. Previous reports demonstrate that amino-acids substitution, resulting from genetic mutations, in ligand binding domain (LBD) of RARA region of PML-RARA were closely related to drug resistance to ATRA therapy. In contrast, for ATO therapy, the molecular mechanisms of the effectiveness and also the resistance are still unclear. Here we identified a PML-RARA that holds double genetic missense mutations in RARA and PML regions, respectively, from an APL patient, who showed clinically resistance to ATRA and ATO therapy. These mutations were observed as his disease progression, and we are interested in the relationship between these mutations with drug resistance to ATRA and/or ATO. AimsAnalyses of the molecular and clinical significance of the double missense mutations of PML-RARA for disease progression and resistance to ATRA and ATO therapy. ResultsEight APL patients were treated with ATO in Nagoya University Hospital, Japan, during ∼5 years from Apr. 1, 2000 to Dec. 31, 2004. One out of 8 patients showed clinically ATO resistance. The patient showing ATO resistance firstly diagnosed as APL (M3 variant) from cytogenetic and chromosomal analyses, and complete remission was obtained after combination chemotherapy with ATRA. Molecular CR was confirmed by RT-PCR analysis, but after 3 month from the induction therapy, ATRA-resistant relapse was observed. After treatment with ATO therapy, response was observed, but the effectiveness was gradually decreased, resulting finally into the resistance. The patient died of disease progression. During his 7 years clinical course, leukemia cells were harvested repeatedly from his bone marrow and peripheral blood. RT-PCR using the total RNA from his tumor cells followed by DNA sequencing was performed, with the result of PML-RARA fusion gene with the bcr3 breakpoint in the intron 3 of PML. When using the tumor cells that were harvested at his terminal stage, a missense point mutation in the LBD of the RARA region of PML-RARA was confirmed. Furthermore, missense point mutation in the PML-B2 domain was also confirmed in the same cDNA clones. Interestingly, these mutations were not observed in the leukemia cells obtained at the onset. These mutations were analyzed in each sample that was obtained as his disease progressed, and some correlation between disease progression and/or the drug resistance and the timing of appearance of these two mutations were suggested. These mutated fusion transcripts were cloned into expression vectors, and we are now analyzing the function relating to the drug resistance and disease progression. ConclusionsDouble genetic missense mutations in the RARA-LBD and PML-B2 of PML-RARA were confirmed in ATRA and ATO resistant patient. These genetic mutations were confirmed in the leukemia cells during his disease progression, and the relationship between those mutations and drug resistances were suggested from the clinical features. Mutations in the PML-B2 domain has not been reported previously, thus, it may be important to show whether this type of mutations are related to the drug resistance, especially to ATO therapy. DisclosuresKiyoi:Novartis Pharma Co. Ltd.: Research Funding; Kyowa Hakko Kirin Co. Ltd.: Consultancy. Naoe:Kyowa Hakko Kirin Co., Ltd. : Research Funding; Chugai Pharmaceutical Co.,Ltd.: Research Funding; Wyeth K.K.: Research Funding.

Modified Z‐transform‐based FDTD algorithm for the anisotropic perfectly matched layer

AbstractA modified Z‐transform‐based algorithm for implementing the D‐H anisotropic perfectly matched layer (APML) is presented for truncating the finite‐difference time‐domain (FDTD) lattices. The main advantage is that, as compared with the previous Z‐transform‐based implementation for the D‐H APML, the proposed algorithm requires less auxiliary variables in the PML regions, and thus the memory requirement and the computational time are saved. These formulations are simple and independent of the material properties of the FDTD computational domain. Two numerical tests have been carried out to validate these formulations. Copyright © 2007 John Wiley & Sons, Ltd.

An Efficient Implementation of the Stretched Coordinate Perfectly Matched Layer

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> An unsplit-field and efficient algorithm to implement the stretched coordinate perfectly matched layer (SC–PML) is proposed for truncating the finite-difference time-domain lattices. The main advantage of the proposed algorithm is that only one auxiliary variable is required in all corners and some edges of the PML regions by means of direct discretizing the second-order differential equation and a memory-minimized algorithm. Two numerical tests have been provided to validate the proposed algorithm. </para>