Common Node Research Articles

An unusual focal atrial tachycardia that simulates a common node reentrant tachycardia: A case report

Focal atrial tachycardia is a relatively uncommon paroxysmal supraventricular tachycardia. Although atrioventricular conduction is regularly 1:1 and the PR interval is often in the normal range, occasionally a 1:1 atrial tachycardia may have a short RP interval, especially when the heart rate is particularly high or the atrioventricular conduction is markedly increased. In these cases, it is necessary to differentiate focal atrial tachycardia from common atrioventricular nodal reentrant tachycardia , which is the most frequent form of paroxysmal supraventricular tachycardia. We describe a case of unusual focal atrial tachycardia with a short RP interval (< 90 ms) in a patient with a marked AV first-degree block which simulates a typical atrioventricular nodal reentrant tachycardia.

Heat capacity and thermodynamic functions of crystalline and amorphous forms of the metal organic framework zinc 2-ethylimidazolate, Zn(EtIm)2

Metal organic frameworks (MOFs) may be useful in a variety of applications, mostly related to their capacity to store gases and catalyze reactions. As several MOFs are mechanically milled, they transition through different structures, progressing toward denser and more energetically stable polymorphs. In this paper, we have measured the constant pressure heat capacities of four zeolitic imidazolate frameworks (ZIFs) based on the 2-ethylimadazolate (EtIm) linker exhibiting identical chemical compositions and different framework structures. Specifically, the crystalline Zn(EtIm)2 frameworks of zeolite rho (RHO), analcime (ANA), and β-quartz (qtz) topologies were compared to each other and to the amorphous form of the material prepared by milling. Molar heat capacities were measured from 1.8 K to 300 K using a Quantum Design Physical Property Measurement System (PPMS), and the data were fit to a sum of theoretical functions below 15 K, orthogonal polynomials from 10 K to 60 K, and a combination of Debye and Einstein functions above 50 K. These fits were then used to generate Cp,m°, Δ0TSm°, Δ0THm°, and Φm° values at smoothed temperatures from 0 K to 300 K. While these MOFs have somewhat different heat capacities reflecting their varying structures, they share an unusual feature in the heat capacity around 100 K that is likely due to some common vibrational behavior related to their common linker and metal node and/or their open frameworks. Though the enthalpies of transition scale with molar volume or density, the entropies of transition show more complex behavior and the Gibbs energies of the three energetically less stable polymorphs (RHO, am-RHO, and ANA) are very similar.

Abstract IA23: Overcoming drug resistance and tumor heterogeneity in gastrointestinal cancers

Abstract Personalized cancer medicine approaches, inhibiting kinases in tumors driven by defined genomic alterations, have demonstrated striking efficacy in many cancer types. However, the development of drug resistance is a major limitation to the efficacy of targeted therapies in oncology. Identifying and understanding the molecular mechanisms driving resistance may foster opportunities to develop therapeutic strategies to overcome resistance. For example, in the ~10% of colorectal cancer patients whose tumors harbor BRAF V600 mutations, we have found that feedback reactivation of MAPK signaling, often mediated by EGFR, underlies the relative insensitivity of these cancers to RAF inhibitors. The development of targeted therapy combination strategies to block feedback reactivation of MAPK signaling has led to marked improvements in response rates for these patients from ~5% to >30% over the past few years. However, in patients who respond to these targeted combinations, the rapid development of acquired resistance still limits clinical benefit. Acquired resistance in BRAF mutant colorectal cancer and in other molecularly-defined tumor types can be marked by the development of extensive molecular heterogeneity due to the selection of sub-clonal tumor cell populations, capable of growing under drug pressures, which poses significant diagnostic and therapeutic challenges. We will present data demonstrating how a single-lesion biopsy at disease progression to diagnose the mechanism of acquired resistance can vastly underrepresent the molecular heterogeneity of resistant tumor clones in an individual patient, and may fail to detect the existence of distinct but important resistance mechanisms that can drive mixed or lesion-specific responses and treatment failure to subsequent targeted therapy. By contrast, liquid biopsy approaches analyzing circulating tumor DNA have the potential to detect the presence of simultaneous resistance mechanisms residing in separate metastases in a single patient and to monitor the effects of subsequent therapies on specific sub-clonal tumor cell populations. These findings highlight the critical role of tumor heterogeneity in driving therapeutic resistance and how convergent targeted therapy strategies blocking common signaling nodes capable of overcoming multiple resistance mechanisms may be needed. Citation Format: Ryan B. Corcoran. Overcoming drug resistance and tumor heterogeneity in gastrointestinal cancers [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA23.

Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program.

Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response.

Laparoscopic Transperitoneal Para-Aortic Lymphadenectomy in 10 Steps

Study ObjectiveLaparoscopic transperitoneal lymphadenectomy has a few advantages. First, it is a minimally invasive approach, and the transperitoneal approach is also the best option when intra-abdominal surgery is indicated. Although the procedure was described more than 2 decades ago, there is a lack of diffusion of the technique. The main objective of this video is standardization and a simple description of the technique. We described this procedure in 10 logical steps, which should help to understand and perform this procedure. MethodsThis video presents a systematic approach to transperitoneal lumboaortic lymphadenectomy, which is clearly divided in 10 steps ordered in a counterclockwise direction. ResultsThe 10 steps are as follows: step 1, retroperitoneal access; step 2, creating a space for subsequent lymphadenectomy and identification of anatomic landmarks; step 3, left common iliac lymph node dissection; step 4, right common iliac lymph node dissection; step 5, presacral lymph node dissection; step 6, lateroaortal lymph node dissection; step 7, laterocaval lymph node dissection; step 8, aortocaval lymph node dissection; step 9, vaginal extraction of bags with specimens; and step 10, vaginal suture. ConclusionsLaparoscopic transperitoneal access to lumboaortic lymph nodes is an effective method of lymphadenectomy, which may bring benefits to a patient and physician. The presented 10 steps help to perform each part of surgery in a logical sequence, making the procedure ergonomic and easier to adopt and learn. Standardization of laparoscopic techniques could help to reduce the learning curve.

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer.

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range.

3D Architecture of Trabecular Bone in the Pig Mandible and Femur: Inter-Trabecular Angle Distributions

Cancellous bone is an intricate network of interconnected trabeculae, to which analysis of network topology can be applied. The inter-trabecular angle (ITA) analysis - an analysis of network topological parameters and regularity of network-forming nodes, was previously carried out on human proximal femora and showed that trabecular bone follows two main principles: sparsity of the network connectedness (prevalence of nodes with low connectivity in the network) and maximal space spanning (angular offset of connected elements is maximal for their number and approximates the values of geometrically symmetric shapes). These observations suggest that 3D organization of trabecular bone, irrespective of size and shape of individual elements, reflects a tradeoff between minimal metabolic cost of maintenance and maximal network stability under conditions of multidirectional loading. In this study we validate the ITA application using additional 3D structures (cork and 3D-printed metal lattices), analyze the ITA parameters in porcine proximal femora and mandibles and carry out a spatial analysis of the most common node type in the porcine mandibular condyle. The validation shows that the ITA application reliably detects designed or evolved topological parameters. The ITA parameters of porcine trabecular bones are similar to those of human bones. We demonstrate functional adaptation in the pig mandibular condyle by showing that the planar nodes with 3 edges are preferentially aligned in relation to the muscle forces that are applied to the condyle. We conclude that the ITA topological parameters are remarkable conserved, but locally do adapt to applied stresses.

Multilayer Spectral Graph Clustering via Convex Layer Aggregation: Theory and Algorithms

Multilayer graphs are commonly used for representing different relations between entities and handling heterogeneous data processing tasks. Nonstandard multilayer graph clustering methods are needed for assigning clusters to a common multilayer node set and for combining information from each layer. This paper presents a multilayer spectral graph clustering (SGC) framework that performs convex layer aggregation. Under a multilayer signal-plus-noise model, we provide a phase transition analysis of clustering reliability. Moreover, we use the phase transition criterion to propose a multilayer iterative model order selection algorithm (MIMOSA) for multilayer SGC, which features automated cluster assignment and layer weight adaptation, and provides statistical clustering reliability guarantees. Numerical simulations on synthetic multilayer graphs verify the phase transition analysis, and experiments on real-world multilayer graphs show that MIMOSA is competitive or better than other clustering methods.

Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF

The CD4+ lineage-specific transcription factor Thpok is required for intrathymic CD4+ T cell differentiation and, together with its homolog LRF, supports CD4+ T cell helper effector responses. However, it is not known whether these factors are needed for the regulatory T cell (Treg) arm of MHC class II responses. In this study, by inactivating in mice the genes encoding both factors in differentiated Tregs, we show that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool. They support IL-2-mediated gene expression and the functions of the Treg-specific factor Foxp3. Accordingly, Treg-specific disruption of Thpok and Lrf causes a lethal inflammatory syndrome similar to that resulting from Treg deficiency. Unlike in conventional T cells, Thpok and LRF functions in Tregs are not mediated by their repression of the transcription factor Runx3. Additionally, we found that Thpok is needed for the differentiation of thymic Treg precursors, an observation in line with the fact that Foxp3+ Tregs are CD4+ cells. Thus, a common Thpok-LRF node supports both helper and regulatory arms of MHC class II responses.

Early clinical outcome of coverage probability based treatment planning for simultaneous integrated boost of nodes in locally advanced cervical cancer

Introduction: More than 50% of patients with locally advanced cervical cancer (LACC) have pathological nodes. Coverage probability (CovP) is a new planning technique allowing for relaxed dose at the boost periphery minimising collateral irradiation. The aim was to report the first early clinical outcome data for CovP based simultaneous integrated boost (SIB) in LACC.Material and methods: Twenty-three consecutive node positive patients were analysed. FIGO stage IB2/IIB/IIIB/IVA/IVB was 1/14/3/1/4. Treatment was radio(chemo)therapy (RT) delivering 45 Gy/25 fx whole pelvis ± para-aortic region (PAN) using volumetric arc therapy (VMAT) followed by magnetic resonance imaging (MRI) guided brachytherapy. PAN RT (13 pts) was given if >2 nodes or if node(s) were present at the common iliac vessels or PAN. Nodal gross tumour volumes (GTV-N) were contoured on both PET-CT and MRI. Clinical target volume (CTV-N) was formed by fusion of GTV-NCT and GTV-NMRI. A 5-mm isotropic margin was used for planning target volume (PTV-N). Nodes in the small pelvis were boosted to 55.0 Gy/25 fx. Common iliac and para-aortic nodes received 57.5 Gy/25 fx. Planning aims for CovP were PTV-N D98 ≥ 90%, CTV-N D98 ≥ 100% and CTV-N D50 ≥ 101.5%.Results: Seventy-four nodes were boosted. A consistent 5.0 ± 0.7 Gy dose reduction from CTV-N D98 to PTV-N D98 was obtained. In total, 73/74 nodes were in complete remission at 3 months PET-CT and MRI. Pelvic control was obtained in 21/23 patients. One patient (IB2, clear cell) had salvageable local disease, while another (IIB) failed in a boosted node. Two patients failed in un-irradiated PAN. One patient age 88 (IIIB) did not receive PAN RT, despite a common iliac node. The other (IIB) recurred above L1. Two further patients (IVB) failed systemically.Conclusion: Since complete remission at 3 months is predictive for favourable long-term nodal control, our study indicates that CovP for SIB is promising.

Synchronous multiple primary gallbladder and gastric malignancies: Report of two cases and review of the literature

Multiple primary malignancies (MPM) are rare. In particular, synchronous gallbladder and gastric malignancies are extremely rare, are associated with a concealed onset and atypical symptoms, and are highly likely to be overlooked or misdiagnosed. The clinical data of two patients with synchronous gallbladder and gastric malignancies are herein reported and integrated with the relevant literature to retrospectively analyze and summarize the pathogenesis and clinical characteristics of MPM. Case 1 was a male 46-year-old patient who underwent laparoscopic cholecystectomy, and succumbed to extensive tumor metastasis 2 months after the operation. Case 2 was an 80-year-old female patient who was treated with distal gastrectomy for gastric cancer, cholecystectomy, gastrojejunostomy and dissection of 5 suprapyloric, 6 subpyloric, 7 left gastric and 8 common hepatic artery lymph nodes, and succumbed to multiple organ failure induced by extensive tumor invasion within 1 week after the operation. Clinical physicians must pay closer attention to early symptoms of MPM in order to make an accurate diagnosis, perform timely radical surgical treatment and achieve favorable therapeutic outcomes, in terms of significantly increasing long-term patient survival rates.

Reliability modeling and analysis of complex multi-state system based on interval fuzzy Bayesian network

With the increasing complexity and large size of modern advanced engineering systems, the traditional reliability analysis and evaluation technology which is based on large number of sample data cannot meet the demand of complex system. Aiming at the engineering application requirement, this paper focuses on the reliability modeling and analysis of complex system with uncertainties and failure dependencies. Due to the diversity of input information and the system failure factors, and system redundancies, the uncertainty and common cause failure (CCF) have become the most important factors for reliability analysis and evaluation of complex system. In consideration of the epistemic uncertainty caused by lack of probability statistical information, the fuzzy theory is employed to express the fuzzy information of system, and the basic events failure probabilities are described by interval-valued fuzzy numbers. Taking account of the influence of CCF to system reliability and the widespread presence of MSS in engineering practices, the CCF is quantified by the β factor parameter model and integrated to Bayesian Network (BN) model through a new defined common cause node. Finally, a comprehensive method for reliability modeling and assessment of a multi-state system (MSS) with CCFs based on interval-valued fuzzy BN is proposed by taking the advantage of graphic representation and uncertainty reasoning of BN. The method has applied to the transmission system of two-axis positioning mechanism of a satellite antenna to demonstrate its effectiveness and capability for directly calculating the system reliability on the basis of multi-state probabilities of components. It has shown that the method proposed has done further improvement of the theory for reliability analysis of complex system and can realize its engineering application.

Scenario tree airline fleet planning for demand uncertainty

This paper proposes an innovative multi-period modeling approach to solve the airline fleet planning problem under demand uncertainty. The problem is modeled using a scenario tree approach. The tree is composed of nodes, which represent points of decision in multiple time stages of the planning horizon, and branches, representing demand variation scenarios. The branches link the decision nodes in consequent time stages and compose scenario paths. Fleet decisions are modeled according to these scenario paths, resembling the real-life process in which fleet plans are not defined in a single moment but instead are adjusted according to the demand development. Given that some scenario paths share common decision nodes, decisions among scenarios need to be synchronized. A mixed-integer linear programming model is proposed to determine the ideal fleet composition for each scenario in the tree and to describe this interdependency between scenarios. Considering the probability of a scenario, fleet composition probabilities for each time-period can be determined. Two real-world based case studies are performed to show the validity of the model. Results show that the proposed scenario tree approach can provide flexible multi-period airline fleet plans, which are more robust to future demand scenarios than fleet solutions obtained using the traditional approach of considering a single deterministic demand evolution scenario.

Skeleton labeled 13C-carbon nanoparticles for the imaging and quantification in tumor drainage lymph nodes.

Carbon nanoparticles (CNPs) have been widely used in tumor drainage lymph node (TDLN) imaging, drug delivery, photothermal therapy, and so on. However, during the theranostic applications, the accumulation efficiency of CNPs in target organs is unknown yet, which largely hinders the extension of CNPs into clinical uses. Herein, we prepared skeleton-labeled 13C-CNPs that had identical properties to commercial CNPs suspension injection (CNSI) for the imaging and quantification in TDLN. 13C-CNPs were prepared by arc discharge method, followed by homogenization with polyvinylpyrrolidone. The size distribution and morphology of 13C-CNPs were nearly the same as those of CNSI under transmission electron microscope. The hydrodynamic radii of both 13C-CNPs and CNSI were similar, too. According to X-ray photoelectron spectroscopy and infrared spectroscopy analyses, the chemical compositions and chemical states of elements were also nearly identical for both labeled and commercial forms. The skeleton labeling of 13C was reflected by the shift of G-band toward lower frequency in Raman spectra. 13C-CNPs showed competitive performance in TDLN imaging, where the three lymph nodes (popliteal lymph node, common iliac artery lymph node, and paraaortic lymph node) were stained black upon the injection into the hind extremity of mice. The direct quantification of 13C-CNPs indicated that 877 μg/g of 13C-CNPs accumulated in the first station of TDLN (popliteal lymph node). The second station of TDLN (common iliac artery lymph node) had even higher accumulation level (1,062 μg/g), suggesting that 13C-CNPs migrated efficiently along lymphatic vessel. The value decreased to 405 μg/g in the third station of TDLN (paraaortic lymph node). Therefore, the 13C-CNPs provided quantitative approach to image and quantify CNSI in biological systems. The implication in biomedical applications and biosafety evaluations of CNSI is discussed.

Abstract 4141: Phosphoproteome networks display consistent hyperactive kinase activity in pancreatic cancer: evidence for new therapeutic options

Abstract Introduction Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its aggressive nature. Patients typically present with distant metastases, at which point cytotoxic agents can extend life expectancy by several months at most. Large-scale phosphoproteomics complements our knowledge obtained from genomics and transcriptomics as it provides information on which proteins and kinases are phosphorylated, thereby implicating pathways that are activated. This approach in cancer research may lead to improved patient selection for treatment with tyrosine kinase inhibitors (TKI). This study is the first to employ phosphotyrosine-based phosphoproteomics on three different preclinical PDAC models as well as patient tumor tissues to understand the aggressive nature of this disease and identify new drug targets. Approach We performed phosphoproteomics on a panel of 11 PDAC cell lines, 7 primary cell cultures, 10 patient-derived xenografts (PDX) and 16 fresh frozen human tumor tissues. Tyrosine phosphopeptides were enriched via immunoprecipitation and phosphopeptides were analyzed by high-resolution nano-LC mass spectrometry. Results Using phosphotyrosine-based phosphoproteomics, we identified a total of 1723 tyrosine phosphorylated proteins and 138 phosphorylated kinases, representing 27% of the kinome. The reproducibility of our workflow was very high, with Pearson correlation coefficients of r = 0.937 for technical replicates of cell lines and r = 0.876 for biological replicates of tumors. In our cell line panels, multiple kinases were commonly highly phosphorylated (e.g. PTK2, EPHA2, EGFR and MET). Functional testing of PTK2 by using TKI defactinib in primary cell lines with high phosphorylation resulted in inhibition of proliferation and migration in vitro. Inhibition of EPHA2 by shRNAs resulted in reduced proliferation in vitro. To validate the relevance of these candidate target proteins in vivo, the tyrosine phosphoproteome of PDXs and human tumors was analyzed. In these tumors, kinase activity analysis based on kinase phosphorylation levels and kinase-substrate networks validated these common active nodes in the majority of these tumors. Conclusion Our extensive tyrosine phosphoproteome analysis spanning a wide range of PDAC models revealed high phosphorylation levels of multiple kinases. Interestingly, the phosphorylated kinase profiles of tumors and cell lines did not show as much heterogeneity as expected, taken into account the existence of biological subtypes in PDAC identified by others via transcriptomics. The aggressive biology of this disease may be correlated with the consistent activation of multiple pathways, some of which we have shown to be targetable in vitro. This study prompts further validation and prognostic evaluation of the identified active kinases to improve treatment of PDAC. Citation Format: Tessa Y. Le Large, Maarten F. Bijlsma, Btissame El Hassouni, Nicolla Funel, Nicole C. van Grieken, Helene Damhofer, Jaco C. Knol, Sander R. Piersma, Thang V. Pham, Henk M. Verheul, Hanneke W. van Laarhoven, Geert Kazemier, Elisa Giovannetti, Connie R. Jimenez. Phosphoproteome networks display consistent hyperactive kinase activity in pancreatic cancer: evidence for new therapeutic options [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4141. doi:10.1158/1538-7445.AM2017-4141

Abstract 103: Blockage of Cdc7/CDK9 signaling sensitizes triple negative breast cancer to EGFR-targeted therapy

Abstract The treatment of Triple-Negative Breast Cancer (TNBC) still represents a profound clinical challenge, the disease being disproportionately responsible for breast cancer-associated deaths. As a consequence, the identification of targeted agents, which synergize with current therapeutic options, is paramount. Resistance to EGFR-tyrosine kinase inhibitors (TKIs), despite frequent EGFR overexpression and reliance on downstream signalling pathways in TNBC, remains endemic. Recent data has also suggested that kinase-inhibition of EGFR in itself is insufficient, given the kinase-independent functions of the protein in transcriptional regulation and DNA-repair may permit prolonged EGFR-mediated signalling in the presence of inhibitors. We performed a kinase inhibitor drug screen (378 kinase inhibitors targeting ~40 different cancer-related kinases) to identify synergistic activity with EGFR inhibition in TNBC. We demonstrate that the dual cdc7/CDK9 inhibitor PHA-767491 synergizes with multiple EGFR-TKIs (Erlotinib, Gefitinib and Lapatinib) in vitro to overcome resistance to EGFR-targeted therapy in various TNBC cell lines. Combined inhibition of EGFR and cdc7/CDK9 resulted in reduced cell proliferation, accompanied by induction of apoptosis and G2-M cell cycle-arrest. Combination therapy inhibited crucial components of the DNA-replicative machinery and also proteins involved in CDK9-mediated transcriptional elongation. Moreover, higher expression of cdc7 and POLR2A was found to be significantly correlated with poorer survival rates in breast cancer patients. Additionally, this synergistic combination effectively inhibited the growth of cells isolated from patient-derived TNBC xenografts under ex vivo culture conditions, highlighting the utility of targeting common transcriptional nodes in cancers addicted to growth factor-mediated signalling pathways. Citation Format: Ronan P. McLaughlin, Jichao He, Vera van der Noord, Jevin Redel, Marcel Smid, Lambert Dorssers, John Martens, John Foekens, Yinghui Zhang, Bob van de Water. Blockage of Cdc7/CDK9 signaling sensitizes triple negative breast cancer to EGFR-targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 103. doi:10.1158/1538-7445.AM2017-103

A multiresolution finite element method based on a new quadrilateral shell element

Initially based on a split node shape function for a quadrilateral shell element, the basic full node shape function is constructed by extending the split node shape function to other three quadrants around the coordinate zero point and a displacement subspace sequence is constituted out of scaling and shifting of the basic full node shape function on the element domain, which brings about a simple, clear and rigorous mathematical basis for the multiresolution analysis (MRA). After that, the multiresolution quadrilateral shell element and method is formulated through applying the minimum potential energy principle. Hence, the MRA concept is established and the resolution level ( RL ) for the element is introduced. Finally, through the numerical examples, the following conclusions are drawn: traditional 4-node quadrilateral shell element and method is essentially a mono-resolution one and also a special case of the proposed element and method. Due to the full nodes in the element domain, the structural model for a numerical analysis by the proposed multiresolution element is an integrated one by RL , not a discretized one by mesh just as by the conventional monoresolution element. The proposed finite element method is a rational MRA method and overperforms all those irrational MRA methods in numerical analysis efficiency, also can consolidate those irrational MRA methods. The clarity of a structural analysis is defined by the RL , not mesh. The continuity of the full node shape functions unveils the secretes behind artificial assemblage of the corresponding items of the stiffness, mass matrices and the equivalent node loading vectors at common nodes by the conventional quadrilateral shell element.

Hierarchical Optimization of Network Resource for Heterogeneous Service in Cloud Scenarios

AbstractWith limited homogeneous and heterogeneous resources in a cloud computing system, it is not feasible to successively expand network infrastructure to adequately support the rapid growth in the cloud service. In this paper, an approach for optimal transmission of hierarchical network for heterogeneous service in Cloud Scenarios was presented. Initially, the theoretical optimal transmission model of a common network was transformed into the hierarchical network with the upper and lower optimization transmission model. Furthermore, the computation simplification and engineering transformation were presented for an approximation method at the low cost of computational complexity. In the final section, the average delay in the engineering method shows its influence on the capability of access for common nodes.

An Optimal Clustering Routing Algorithm for Wireless Sensor Networks with Small-World Property

In the wireless sensor networks, deploying a small amount of heterogeneous nodes which directly communicate with the Sink node, can form shortcuts. The shortcuts can make the network to have small-world properties, which can save energy and improve network performance. In the large-scale networks, the optimal deployment of heterogeneous nodes is a NP-hard problem. Considering the total energy consumption of the network and the uniformity of each node energy consumption, this paper presents a clustering heterogeneous network routing algorithm which based on mixed integer programming (CHNMIP). Firstly, the algorithm supposes that the heterogeneous nodes can only be placed in the position of the common nodes and converts the optimal deployment of heterogeneous nodes into a mixed integer programming problem, and finds out the approximate optimal solution using Lagrangian relaxation and Benders decomposition algorithm. Then, it dynamically divides common nodes into clusters, and sets the appropriate transmission. Finally, it theoretically analyzes the performance of CHNMIP routing algorithm, and the simulation results also show that CHNMIP routing algorithm can better improve the network performance in different simulation environment.

A O(m) Self-Stabilizing Algorithm for Maximal Triangle Partition of General Graphs

The triangle partition problem is a generalization of the well-known graph matching problem consisting of finding the maximum number of independent edges in a given graph, i.e., edges with no common node. Triangle partition instead aims to find the maximum number of disjoint triangles. The triangle partition problem is known to be NP-complete. Thus, in this paper, the focus is on the local maximization variant, called maximal triangle partition (MTP). Thus, paper presents a new self-stabilizing algorithm for MTP that converges in O(m) moves under the unfair distributed daemon.