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| 2. |
- Strosberg, J., et al.
(författare)
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Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)
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| 3. |
- Cheung, BB, et al.
(författare)
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A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma
- 2021
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:13, s. 2367-2381
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Tidskriftsartikel (refereegranskat)abstract
- Histone deacetylase (HDAC) inhibitors are effective in MYCN-driven cancers, because of a unique need for HDAC recruitment by the MYCN oncogenic signal. However, HDAC inhibitors are much more effective in combination with other anti-cancer agents. To identify novel compounds which act synergistically with HDAC inhibitor, such as suberanoyl hydroxamic acid (SAHA), we performed a cell-based, high-throughput drug screen of 10,560 small molecule compounds from a drug-like diversity library and identified a small molecule compound (SE486-11) which synergistically enhanced the cytotoxic effects of SAHA. Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines. Treatment with SAHA and SE486-11 increased MYCN ubiquitination and degradation, and markedly inhibited tumorigenesis in neuroblastoma xenografts, and, MYCN transgenic zebrafish and mice. The combination reduced ubiquitin-specific protease 5 (USP5) levels and increased unanchored polyubiquitin chains. Overexpression of USP5 rescued neuroblastoma cells from the cytopathic effects of the combination and reduced unanchored polyubiquitin, suggesting USP5 is a therapeutic target of the combination. SAHA and SE486-11 directly bound to USP5 and the drug combination exhibited a 100-fold higher binding to USP5 than individual drugs alone in microscale thermophoresis assays. MYCN bound to the USP5 promoter and induced USP5 gene expression suggesting that USP5 and MYCN expression created a forward positive feedback loop in neuroblastoma cells. Thus, USP5 acts as an oncogenic cofactor with MYCN in neuroblastoma and the novel combination of HDAC inhibitor with SE486-11 represents a novel therapeutic approach for the treatment of MYCN-driven neuroblastoma.
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| 4. |
- Craeye, C., et al.
(författare)
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Macro Basis Function Framework for Solving Maxwell’s Equations in Surface Integral Equation Form
- 2014
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Ingår i: The FERMAT Journal. ; 3, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- The Macro Basis Functions (MBFs) approach is aform of domain-decomposition method applied to radiation andscattering problems solved by using integral-equation techniques.It enables a systematic reduction of the number of degrees offreedom, from that imposed by the discretization of the surfacesto that associated with the physical limits of field distributions.This paper reviews different variants of this approach, includingthe techniques for determining the MBFs and for fast calculationof their interactions. The link with Krylov-subspace iterativemethods is described, the relationship between the surface ofsubdomains and the number of physical degrees of freedom isdiscussed and multi-level schemes are revisited. Finally, avenuesfor further research are outlined in the Conclusions section ofthis paper.
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| 5. |
- Dalarsson, Masoud, et al.
(författare)
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Analytical approach to modeling flat lenses with continuously graded profiles
- 2015
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Ingår i: 2015 USNC-URSI Radio Science Meeting (Joint with AP-S Symposium), USNC-URSI 2015 - Proceedings. - : IEEE.
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Konferensbidrag (refereegranskat)abstract
- In this work we present an analytical approach to deriving the field solutions for a class of flat lenses that have attracted the attentions of antenna designers and researchers alike. The lens designs typically consist of a number of layers of graded index dielectrics, whose properties may vary in both the radial and longitudinal directions. The fields propagating in the longitudinal direction through the central layer primarily contribute to the bulk of the phase, while the side layers act as matching layers and help reduce the reflections originating at the interfaces of the middle layer. We model such lenses as compact composites with material properties characterized by continuous permittivity and permeability functions, which tend asymptotically to unity at the boundaries of the composite cylinder.
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| 6. |
- Ludick, D. J., et al.
(författare)
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A comparison of domain decomposition techniques for analysing disjoint finite antenna arrays
- 2014
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Ingår i: 8th European Conference on Antennas and Propagation, EuCAP 2014. - 2164-3342. - 9788890701849 ; , s. 2411-2415
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Konferensbidrag (refereegranskat)abstract
- The purpose of this work is to present a quantitative comparison between three Method-of-Moments based domain decomposition techniques that are used for the analysis of large, disjoint finite antenna arrays. The methods considered are the Characteristic Basis Function Method, the Domain Green's Function Method, and a newly proposed improved version of the DGFM, i.e., the i-DGFM. The computational complexities of the techniques are compared in terms of runtime and memory usage. Both active and passive antenna arrays are considered.
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| 7. |
- Ludick, D. J., et al.
(författare)
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Applying the CBFM-enhanced domain Green's function method to the analysis of large disjoint subarray antennas
- 2013
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Ingår i: Proceedings of the 2013 International Conference on Electromagnetics in Advanced Applications, ICEAA 2013. - 9781467357074 ; , s. 94-97
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Konferensbidrag (refereegranskat)abstract
- This paper considers the efficient numerical analysis of large, finite antenna arrays comprising of disjoint subarrays by using the Domain Green's Function Method (DGFM) [1] in conjunction with the Characteristic Basis Function Method (CBFM) [2]. In the CBFM-enhanced DGFM we consider large arrays consisting of multiple disjoint subarrays and impose the infinite array type assumption, i.e. that the currents on subarrays are identical except for a complex-valued scaling factor. Scan impedance matrices are then constructed for each of the subarrays from the block-partitioned CBFM reduced impedance matrix which account for the mutual coupling in the array environment. Runtime and memory usage scale efficiently for the CBFM-enhanced DGFM as we limit the computational complexity to that required to analyse a single subarray. The paper discusses the hybridisation of the DGFM with the CBFM, and illustrates the results of applying the proposed solution technique to an example consisting of a large finite array of disjoint subarrays. © 2013 IEEE.
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| 8. |
- Ludick, D. J., et al.
(författare)
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Efficient Analysis of Large Aperiodic Antenna Arrays Using the Domain Green's Function Method
- 2014
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Ingår i: IEEE Transactions on Antennas and Propagation. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-926X .- 1558-2221. ; 62:4, s. 1579-1588
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Tidskriftsartikel (refereegranskat)abstract
- An efficient method-of-moments (MoM) based domain decomposition technique, viz., the domain Green's function method (DGFM), is presented for analyzing large antenna arrays. The DGFM is a perturbation technique where mutual coupling between array elements is accounted for during the formulation of an active impedance matrix for each domain/array element. The active current distribution on the entire array geometry is obtained by solving the smaller matrix equations related to the elements, and not that of the problem as a whole. This leads to a significant saving in both runtime and memory usage. The method also takes into account the edge effects attributed to the finite size of the array, complex excitations with nonlinear phase shift and is not limited to periodic array configurations. The DGFM is an approximation and assumes a slowly varying current distribution between domains. A novel way to mitigate the aforementioned, by including secondary coupling effects, is also discussed. Furthermore, an efficient active impedance matrix fill strategy is presented where the active impedance matrix summation is truncated to include only a certain number of terms. Parallelization using both distributed and shared memory programming models have also been applied to the DGFM, to further optimize runtime and memory usage.
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| 9. |
- Maaskant, Rob, 1978, et al.
(författare)
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Multi-level characteristic basis function method (MLCBFM) for the anaylsis of large antenna arrays
- 2011
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Ingår i: Radio Science Bulletin. - 1024-4530. ; 336:3, s. 23-34
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Tidskriftsartikel (refereegranskat)abstract
- A multi-level version of the Characteristic Basis Function Method (CBFM) is presented for computing the input impedance matrix and radiation patterns of very large antenna arrays. Specifically, we consider the challenging problem of an electrically large subarray that is surrounded by (many) other disjoint subarrays, and solve this problem by employing a two-level Characteristic Basis Function Method. At level zero, Rao-Wilton-Glisson (RWG) basis functions are employed to locally synthesis the surface current. Next, the number of degrees of freedom (DoFs) for the current is reduced at level one by employing the characteristic basis functions (CBFs), each of which is a macro basis function supported by an antenna element, and is a fixed combination of RWG basis functions. Moreover, the characteristic basis functions at level two are supported by subarrays to further reduce the degrees of freedom. This multilevel approach is memory efficient and generates a final reduced matrix equation that can be solved directly, i.e., in-core through standard Gaussian elimination techniques, even though the conventional MoM (Method of Moments) formulation of the same problem may require more than one million RWG basis functions. Numerical examples are presented for various array sizes, including a 25 subarray problem comprised of 64 tapered-slot antennas (TSAs) each. The proposed method demonstrates very good accuracy, numerical efficiency, and a reduced memory storage requirement.
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| 10. |
- Marinovic, Tomislav, et al.
(författare)
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Comparison of CBFM-Enhanced Iterative Methods for MoM-Based Finite Antenna Array Analysis
- 2022
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Ingår i: IEEE Transactions on Antennas and Propagation. - 0018-926X .- 1558-2221. ; 70:5, s. 3538-3548
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we compare different iterative techniques enhanced by the CBFM, that are used to analyze finite arrays of disjoint antenna elements. These are based on the stationary-type methods (Jacobi, Gauss-Seidel, macro-block Jacobi), the nonstationary GMRES and the hybrid alternating GMRES-Jacobi (AGJ) method which combines these two types. In each iteration, the reduced CBFM system is constructed based on the previous iterates, the solution of which is used to update the solution vector in the next iteration with improved accuracy. In this way, the convergence of the classical iterative techniques can be greatly improved. The convergence rates and computational costs of the CBFM-enhanced iterative methods are analyzed by considering several MoM-based problems. The GMRES-based method, which employs the block-Jacobi preconditioner, outperforms the other methods when the MoM matrix is ill-conditioned. For well-conditioned MoM matrices with reduced diagonal dominance due to increased presence of the inter-element coupling effects, the AGJ method or the methods based on the stationary-type iterations may require smaller computational effort to converge to the desired solution accuracy in comparison to the GMRES-based approach.
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