bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimode Analysis of the Dynamics and Integrity of Electrically Actuated MEMS Resonators
Authors: Yamgoué Serge Bruno , Tchiegang Alain Juvenal
Published: September 2014

We present a theoretical investigation of the dynamic behavior of a microelectromechanical system (in brief, MEMS) device modelled as a clamped-clamped microbeam subjected to electrostatic and electrodynamic actuation. We use the Galerkin projection
technique to reduce the partial integro-differential equation governing the dynamics of the microbeam to a system of coupled ordinary differential equations which describe the interactions of the linear mode shapes of the microbeam. Analytical solutions are derived and their stability is studied for the simplest reduced-order model which takes into account only the first linear mode in the Galerkin procedure. We further investigate the influence of the first few higher modes on the Galerkin procedure, and hence its convergence, by analysing the boundaries between pull-in and pull-in-free vibrations domains in the space of actuation parameters. These are determined for the various multimode combinations using direct numerical time integration. Our results show that unsafe domains form V-like shapes for actuation frequencies close to the superharmonic, fundamental, and subharmonic resonances. They also reveal that the single first-mode reduced model usually considered underestimates the left branches and overestimates the right branches of these boundaries.
Efficiency Enhancement on Thermal Comfort Assessment of Indoor Space with Air‐Conditioner Using Computational Analysis
Authors: Chou Yu-Tuan , Hsia Shao-Yi , Lee Bi-Wen
Published: September 2014

Thermal comfort providing is one of the biggest uses of energy in building. For giving better human comfort, the suitable operation conditions of air‐conditioner are the most important. The quick and right approach is necessary. In this paper, a small office is studied to improve office staff staying for a long period of time and achieve the thermal comfort environment for reducing energy consumption. Commercial software,
Solidworks, is utilized for modeling the facilities and the Flow Simulation module for analyzing the air properties of the indoor space. Four types of air‐conditioner operation are applied to set the simulated conditions, including exterior temperature, outlet temperature and wind speed of air‐conditioner, and location of air‐conditioner. Predicted mean vote (PMV) and predicted percent dissatisfied (PPD) at specific office areas are further acquired through dynamic anthropometry. For seeking the optimal control factors, both of the full factorial method and Taguchi method are utilized to obtain the PMV of specified location. The analyzed result shows the evaluation speed
of indoor thermal comfort by Taguchi method is faster than the full‐factorial method. It is concluded that software simulation with Taguchi method shows the successful implementation and higher efficiency for thermal comfort
assessment.
Ant Colony Algorithm and Simulation for Robust Airport Gate Assignment
Authors: Zhao Hui , Cheng Liqin
Published: September 2014

Airport gate assignment is core task for airport ground operations. Due to the fact that the departure and arrival time of flights may be influenced by many random factors, the airport gate assignment scheme may encounter gate conflict and many other problems. This paper aims at finding a robust solution for airport gate assignment problem. A mixed integer model is proposed to formulate the problem, and colony algorithm is designed to solve this model. Simulation result shows that, in consideration of robustness, the ability of antidisturbance for airport gate assignment scheme has much improved.
Improving Accuracy and Scalability of Personal Recommendation Based on Bipartite Network Projection
Authors: Yin Fengjing , Zhao Xiang , Zhang Xin , Ge Bin , Xiao Weidong
Published: September 2014

Bipartite network projection method has been recently employed for personal recommendation. It constructs a bipartite network between users and items. Treating user taste for items as resource in the network, we allocate the resource via links between user nodes and item nodes. However, the taste model employed by existing algorithms cannot differentiate “dislike” and “unrated” cases implied by user ratings. Moreover, the distribution of resource is solely based on node degrees, ignoring the different transfer rates of the links. To enhance the performance, this paper devises a negative‐aware and rating‐integrated algorithm on top of the baseline algorithm. It enriches the current user taste model to encompass “like,” “dislike,” and “unrated” information from users. Furthermore, in the resource distribution stage, we propose to initialize the resource allocation according to user ratings, which also determines the resource transfer rates on links afterward. Additionally, we also present a scalable implementation in the MapReduce framework by parallelizing the algorithm. Extensive experiments conducted on real data validate the effectiveness and efficiency of the proposed algorithms.
Rotor Resistance Online Identification of Vector Controlled Induction Motor Based on Neural Network
Authors: Fan Bo , Yang Zhixin , Xu Wei , Wang Xianbo
Published: September 2014

Rotor resistance identification has been well recognized as one of the most critical factors affecting the theoretical study and applications of AC motor’s control for high performance variable frequency speed adjustment. This paper proposes a novel model for rotor resistance parameters identification based on Elman neural networks. Elman recurrent neural network is capable of performing nonlinear function approximation and possesses the ability of time‐variable characteristic adaptation. Those influencing factors of specified parameter are analyzed, respectively, and various work states are covered to ensure the completeness of the training samples. Through signal preprocessing on samples and training dataset, different input parameters identifications with one network are compared and analyzed. The trained Elman neural network, applied in the identification model, is able to efficiently predict the rotor resistance in high accuracy. The simulation and experimental results show that the proposed method owns extensive adaptability and performs very well in its application to vector controlled induction motor. This identification method is able to enhance the performance of induction motor’s variable‐frequency speed regulation.
A Hybrid Finite Element‐Fourier Spectral Method for Vibration Analysis of Structures with Elastic Boundary Conditions
Authors: Li Wan-You , Lv Binglin , Ouyang Huajiang , Du Jingtao , Zhou Haijun , Wang Donghua
Published: September 2014

A novel hybrid method, which simultaneously possesses the efficiency of Fourier spectral method (FSM) and the applicability of the finite element method (FEM), is presented for the vibration analysis of structures with elastic boundary conditions. The FSM, as one type of analytical approaches with excellent convergence and accuracy, is mainly limited to problems with relatively regular geometry. The purpose of the current study is to extend the FSM to problems with irregular geometry via the FEM and attempt to take full advantage of the FSM and the conventional FEM for structural vibration problems. The computational domain of general shape is divided into several subdomains firstly, some of which are represented by the FSM while the rest by the FEM. Then, fictitious springs are introduced for connecting these subdomains. Sufficient details are given to describe the development of such a hybrid method. Numerical examples of a one‐dimensional Euler‐Bernoulli beam and a two‐dimensional rectangular plate show that the present method has good accuracy and efficiency. Further, one irregular‐shaped plate which consists of one rectangular plate and one semi‐circular plate also demonstrates the capability of the present method applied to irregular structures.
Measuring Technological Progress of Smart Grid Based on Production Function Approach
Authors: Han Dong , Yan Zheng
Published: September 2014

Production function theory combined with data envelopment analysis (DEA) and ridge regression analysis (RRA) is applied to evaluate the technological progress of the smart grid. The feasible conditions of production function models are determined by the DEA algorithm. RRA is applied to estimate the relevant parameters of the evaluation models under study. One of the significant steps in the design of the assessment algorithm is the structure of production function models. Therefore, the Cobb‐Douglas, constant elasticity of substitution, and translog production functions are employed to evaluate the technological progress of the smart grid, respectively. The results of analysis and calculation mainly include the DEA relative efficiency, slacks in inputs and outputs of inefficient units, estimated parameters, and quantitative indices of technological progress.
A Double Evolutionary Pool Memetic Algorithm for Examination Timetabling Problems
Authors: Lei Yu , Gong Maoguo , Jiao Licheng , Li Wei , Zuo Yi , Cai Qing
Published: September 2014

A double evolutionary pool memetic algorithm is proposed to solve the examination timetabling problem. To improve the performance of the proposed algorithm, two evolutionary pools, that is, the main evolutionary pool and the secondary evolutionary pool, are employed. The genetic operators have been specially designed to fit the examination timetabling problem. A simplified version of the simulated annealing strategy is designed to speed the convergence of the algorithm. A clonal mechanism is introduced to preserve population diversity. Extensive experiments carried out on 12 benchmark examination timetabling instances show that the proposed algorithm is able to produce promising results for the uncapacitated examination timetabling problem.
A Novel Closed‐Form Solution for Circular Openings in Generalized Hoek‐Brown Media
Authors: Meng Qing Xiang , Wang Wei
Published: September 2014

A novel closed‐form solution is presented in this paper for the estimation of displacements around circular openings in a brittle rock mass subject to a hydrostatic stress field. The rock mass is assumed to be elastic‐brittle‐plastic media governed by the generalized Hoek‐Brown yield criterion. The present closed‐form solution was validated by employing the existing analytical solutions. Results of several example cases are analyzed to show that, with the simplified assumption, a novel closed‐form solution is derived and found to be in an excellent agreement with those obtained by using the exact integration method with mathematical software. Parametric sensitivity analysis is carried out and the parameter ar tends to be the sensitive factor. As a closed‐form solution that does not require transformation technique and the use of any numerical method, this work can provide a better choice in the preliminary design for circular opening.
Sample Data Synchronization and Harmonic Analysis Algorithm Based on Radial Basis Function Interpolation
Authors: Zhang Huaiqing , Chen Yu , Fu Zhihong , Liu Ran
Published: September 2014

The spectral leakage has a harmful effect on the accuracy of harmonic analysis for asynchronous sampling. This paper proposed a time quasi‐synchronous sampling algorithm which is based on radial basis function (RBF) interpolation. Firstly, a fundamental period is evaluated by a zero‐crossing technique with fourth‐order Newton’s interpolation, and then, the sampling sequence is reproduced by the RBF interpolation. Finally, the harmonic parameters can be calculated by FFT on the synchronization of sampling data. Simulation results showed that the proposed algorithm has high accuracy in measuring distorted and noisy signals. Compared to the local approximation schemes as linear, quadric, and fourth‐order Newton interpolations, the RBF is a global approximation method which can acquire more accurate results while the time‐consuming is about the same as Newton’s.
Combined Use of Clips and Nylon Snare (“Tulip-Bundle”) as a Rescue Endoscopic Bleeding Control in a Mallory-Weiss Syndrome
Authors: Ivekovic Hrvoje , Radulovic Bojana , Jankovic Suzana , Markos Pave , Rustemovic Nadan
Published: September 2014

Mallory-Weiss syndrome (MWS) accounts for 6–14% of all cases of upper gastrointestinal bleeding. Prognosis of patients with MWS is generally good, with a benign course and rare recurrence of bleeding. However, no strict recommendations exist in regard to the mode of action after a failure of primary endoscopic hemostasis. We report a case of an 83-year-old male with MWS and rebleeding after the initial endoscopic treatment with epinephrine and clips. The final endoscopic control of bleeding was achieved by a combined application of clips and a nylon snare in a “tulip-bundle” fashion. The patient had an uneventful postprocedural clinical course and was discharged from the hospital five days later. To the best of our knowledge, this is the first case report showing the “tulip-bundle” technique as a rescue endoscopic bleeding control in the esophagus.
Cancer-Associated Adipose Tissue Promotes Breast Cancer Progression by Paracrine Oncostatin M and Jak/STAT3 Signaling
Authors: Lapeire Lore , Hendrix An , Lambein Kathleen , Van Bockstal Mieke , Braems Geert , Van Den Broecke Rudy , Limame Ridha , Mestdagh Pieter , Vandesompele Jo , Vanhove Christian , Maynard Dawn , Lehuédé Camille , Muller Catherine , Valet Philippe , Gespach Christian P. , Bracke Marc , Cocquyt Veronique , Denys Hannelore , De Wever Olivier
Published: September 2014

Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer–associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45+ leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-) Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705. Cancer Res; 74(23); 6806–19. ©2014 AACR.
A Recurrent Activating PLCG1 Mutation in Cardiac Angiosarcomas Increases Apoptosis Resistance and Invasiveness of Endothelial Cells
Authors: Kunze Kristin , Spieker Tilmann , Gamerdinger Ulrike , Nau Kerstin , Berger Johannes , Dreyer Thomas , Sindermann Jürgen R. , Hoffmeier Andreas , Gattenlöhner Stefan , Bräuninger Andreas
Published: September 2014

Primary cardiac angiosarcomas are rare tumors with unfavorable prognosis. Pathogenic driver mutations are largely unknown. We therefore analyzed a collection of cases for genomic aberrations using SNP arrays and targeted next-generation sequencing (tNGS) of oncogenes and tumor-suppressor genes. Recurrent gains of chromosome 1q and a small region of chromosome 4 encompassing KDR and KIT were identified by SNP array analysis. Repeatedly mutated genes identified by tNGS were KDR with different nonsynonymous mutations, MLL2 with different nonsense mutations, and PLCG1 with a recurrent nonsynonymous mutation (R707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases. PLCγ1 is usually activated by Y783 phosphorylation and activates protein kinase C and Ca2+-dependent second messengers, with effects on cellular proliferation, migration, and invasiveness. Ectopic expression of the PLCγ1-R707Q mutant in endothelial cells revealed reduced PLCγ1-Y783 phosphorylation with concomitant increased c-RAF/MEK/ERK1/2 phosphorylation, increased IP3 amounts, and increased Ca2+-dependent calcineurin activation compared with ectopic expressed PLCγ1-wild-type. Furthermore, cofilin, whose activation is associated with actin skeleton reorganization, showed decreased phosphorylation, and thus activation after expression of PLCγ1-R707Q compared with PLCγ1-wild-type. At the cellular level, expression of PLCγ1-R707Q in endothelial cells had no influence on proliferation rate, but increased apoptosis resistance and migration and invasiveness in in vitro assays. Together, these findings indicate that the PLCγ1-R707Q mutation causes constitutive activation of PLCγ1 and may represent an alternative way of activation of KDR/PLCγ1 signaling besides KDR activation in angiosarcomas, with implications for VEGF/KDR targeted therapies. Cancer Res; 74(21); 6173–83. ©2014 AACR.
Coordinate Hyperactivation of Notch1 and Ras/MAPK Pathways Correlates with Poor Patient Survival: Novel Therapeutic Strategy for Aggressive Breast Cancers
Authors: Mittal Suruchi , Sharma Ankur , Balaji Sai A. , Gowda Manju C. , Dighe Rajan R. , Kumar Rekha V. , Rangarajan Annapoorni
Published: September 2014

Aberrant activation of Notch and Ras pathways has been detected in breast cancers. A synergy between these two pathways has also been shown in breast cell transformation in culture. Yet, the clinical relevance of Notch–Ras cooperation in breast cancer progression remains unexplored. In this study, we show that coordinate hyperactivation of Notch1 and Ras/MAPK pathways in breast cancer patient specimens, as assessed by IHC for cleaved Notch1 and pErk1/2, respectively, correlated with early relapse to vital organs and poor overall survival. Interestingly, majority of such Notch1highErkhigh cases encompassed the highly aggressive triple-negative breast cancers (TNBC), and were enriched in stem cell markers. We further show that combinatorial inhibition of Notch1 and Ras/MAPK pathways, using a novel mAb against Notch1 and a MEK inhibitor, respectively, led to a significant reduction in proliferation and survival of breast cancer cells compared with individual inhibition. Combined inhibition also abrogated sphere-forming potential, and depleted the putative cancer stem-like cell subpopulation. Most importantly, combinatorial inhibition of Notch1 and Ras/MAPK pathways completely blocked tumor growth in a panel of breast cancer xenografts, including the TNBCs. Thus, our study identifies coordinate hyperactivation of Notch1 and Ras/MAPK pathways as novel biomarkers for poor breast cancer outcome. Furthermore, based on our preclinical data, we propose combinatorial targeting of these two pathways as a treatment strategy for highly aggressive breast cancers, particularly the TNBCs that currently lack any targeted therapeutic module. Mol Cancer Ther; 13(12); 3198–209. ©2014 AACR.
Antitumor Effects of a Novel Small Molecule Targeting PCNA Chromatin Association in Prostate Cancer
Authors: Dillehay Kelsey L. , Lu Shan , Dong Zhongyun
Published: September 2014

Proliferating cell nuclear antigen (PCNA) plays an essential role in DNA replication and repair. Tumor cells express high levels of PCNA, identifying it as a potentially ideal target for cancer therapy. Previously, we identified nine compounds termed PCNA inhibitors (PCNA-Is) that bind directly to PCNA, stabilize PCNA trimer structure, reduce chromatin-associated PCNA, and selectively inhibit tumor cell growth. Of these compounds, PCNA-I1 is most potent. The purposes of this study were to further investigate the effects of targeting PCNA chromatin association on DNA damage and cytotoxicity and to evaluate the therapeutic potential of PCNA-I1 against tumors in mice. Given the important roles of tumor suppressor p53 in regulating sensitivity of tumor cells to chemotherapeutics, we performed studies in two human prostate cancer cell lines differing in p53 expression: LNCaP cells (wild-type p53) and PC-3 cells (p53-null). PCNA-I1 induced DNA damage and apoptosis in both LNCaP and PC-3 cells and enhanced DNA damage and apoptosis triggered by cisplatin. PCNA-I1 also induced autophagy in PC-3 cells. A short-term pretreatment with PCNA-I1 reduced colony formation by 50% in both cell lines. These data suggest that, unlike many other cytotoxic drugs, the effects of PCNA-I1 on tumor cells do not depend on expression of p53. Intravenous administrations of PCNA-I1 significantly retarded growth of LNCaP tumors of in nude mice without causing detectable effects on mouse body weight and hematology profiles. These data provide proof of concept that targeting PCNA chromatin association could be a novel and effective therapeutic approach for treatment of cancer. Mol Cancer Ther; 13(12); 2817–26. ©2014 AACR.
A p53/ARF-Dependent Anticancer Barrier Activates Senescence and Blocks Tumorigenesis without Impacting Apoptosis
Authors: Sinha Vidya C. , Qin Lan , Li Yi
Published: September 2014

In response to oncogene activation and oncogene-induced aberrant proliferation, mammalian cells activate apoptosis and senescence, usually via the p53–ARF tumor-suppressor pathway. Apoptosis is a known barrier to cancer and is usually downregulated before full malignancy, but senescence as an anticancer barrier is controversial due to its presence in the tumor environment. In addition, senescence may aid cancer progression via releasing senescence-associated factors that instigate neighboring tumor cells. Here, it is demonstrated that apoptosis unexpectedly remains robust in ErbB2 (ERBB2/HER2)-initiated mammary early lesions arising in adult mice null for either p53 or ARF. These early lesions, however, downregulate senescence significantly. This diminished senescence response is associated with accelerated progression to cancer in ARF-null mice compared with ARF–wild-type mice. Thus, the ARF–p53 pathway is dispensable for the apoptosis anticancer barrier in the initiation of ErbB2 breast cancer, the apoptosis barrier alone cannot halt mammary tumorigenesis, and senescence is a key barrier against carcinogenesis.

Implications: Findings in this relevant mouse model of HER2-driven breast cancer suggest that effective prevention relies upon preserving both ARF/p53–independent apoptosis and ARF/p53–dependent senescence. Mol Cancer Res; 13(2); 231–8. ©2014 AACR.
PARP1-Driven Poly-ADP-Ribosylation Regulates BRCA1 Function in Homologous Recombination–Mediated DNA Repair
Authors: Hu Yiduo , Petit Sarah A. , Ficarro Scott B. , Toomire Kimberly J. , Xie Anyong , Lim Elgene , Cao Shiliang A. , Park Eunyoung , Eck Michael J. , Scully Ralph , Brown Myles , Marto Jarrod A. , Livingston David M.
Published: September 2014

BRCA1 promotes homologous recombination–mediated DNA repair (HRR). However, HRR must be tightly regulated to prevent illegitimate recombination. We previously found that BRCA1 HRR function is regulated by the RAP80 complex, but the mechanism was unclear. We have now observed that PARP1 interacts with and poly-ADP-ribosylates (aka PARsylates) BRCA1. PARsylation is directed at the BRCA1 DNA binding domain and downmodulates its function. Moreover, RAP80 contains a poly-ADP-ribose–interacting domain that binds PARsylated BRCA1 and helps to maintain the stability of PARP1–BRCA1–RAP80 complexes. BRCA1 PARsylation is a key step in BRCA1 HRR control. When BRCA1 PARsylation is defective, it gives rise to excessive HRR and manifestations of genome instability. BRCA1 PARsylation and/or RAP80 expression is defective in a subset of sporadic breast cancer cell lines and patient-derived tumor xenograft models. These observations are consistent with the possibility that such defects, when chronic, contribute to tumor development in BRCA1+/+ individuals.

Significance: We propose a model that describes how BRCA1 functions to both support and restrict HRR. BRCA1 PARsylation is a key event in this process, failure of which triggers hyper-recombination and chromosome instability. Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions. Cancer Discov; 4(12); 1430–47. ©2014 AACR.

This article is highlighted in the In This Issue feature, p. 1355
Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations
Authors: Anık Ahmet , Kersseboom Simone , Demir Korcan , Çatlı Gönül , Yiş Uluç , Böber Ece , van Mullem Alies , van Herebeek Ramona E.A. , Hız Semra , Abacı Ayhan , Visser Theo J.
Published: September 2014

Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.
Multiple-Dose Up-Titration Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Selexipag, an Orally Available Selective Prostacyclin Receptor Agonist, in Healthy Subjects
Authors: Bruderer Shirin , Hurst Noémie , Kaufmann Priska , Dingemanse Jasper
Published: September 2014

Objective: The objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of selexipag, an orally available selective prostacyclin receptor agonist, in development for pulmonary arterial hypertension in healthy subjects. Methods: This was a double-blind, placebo-controlled, randomised, multiple-ascending-dose, up-titration study. Male subjects received increasing oral doses of selexipag (400-1,800 µg; n = 12) or placebo (n = 4) twice daily for 3 days each, using incremental steps of 200 µg between each dose level. Standard safety and tolerability data were collected. Blood samples were taken to assess the pharmacokinetics of selexipag and its active metabolite ACT-333679 and possible effects on platelet aggregation. Results: Dose levels of selexipag up to 1,600 μg were well tolerated and this dose was identified as the maximum tolerated dose. Plasma exposure to ACT-333679 was approximately 4 times higher than that to selexipag. Steady-state conditions for both compounds were reached on day 3 of each dose level, and no accumulation of selexipag or ACT-333679 was observed. Based on the area under the curve and the maximum plasma concentration, the pharmacokinetics of selexipag and ACT-333679 were dose proportional. At the highest dose level, the geometric mean terminal half-life of selexipag and ACT-333679 was 1.4 and 8.7 h, respectively. The observed effects on platelet aggregation were variable without obvious drug- or dose-dependent pattern. Conclusions: Oral administration of increasing doses of selexipag was well tolerated. The present results support the conduct of future clinical trials.
Giant Pyogenic Granuloma in a Patient with Chronic Lymphocytic Leukemia
Authors: Plovanich Molly , Tsibris Hillary C. , Lian Christine G. , Mostaghimi Arash
Published: September 2014

Pyogenic granuloma, also known as lobular capillary hemangioma, is a common benign vascular proliferative lesion that can present at any age on the skin or mucous membranes. Most lesions do not exceed 2 cm, but there are a handful of giant cutaneous pyogenic granulomas that have been reported, often in individuals with underlying immune dysfunction. Here, we report the first giant pyogenic granuloma in a patient with a hematological malignancy, chronic lymphocytic leukemia.
Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology
Authors: Ong Sang-Bing , Hall Andrew , Dongworth Rachel , Kalkhoran Siavash , Pyakurel Aswin , Scorrano Luca , Hausenloy Derek
Published: September 2014

The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0.05). This effect was associated with delayed time taken to induce mitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: p< 0.05); and reduced cell death following simulated IRI (32.8 ± 1.2 % caAkt vs 63.8 ± 5.6 % control: N=320 cells/group: p< 0.05). Similar effects on mitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: p< 0.05), and reduced the proportion of cells displaying myofibrillar disarray and mitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; p< 0.05). In conclusion, we found that either genetic or pharmacological activation of Akt protected the heart against acute ischaemia-reperfusion injury by modulating mitochondrial morphology.
O poeta da experimentação: Augusto de Campos e a crise do verso
Authors: Rebechi Junior Arlindo
Published: September 2014

Apresentação do poeta Augusto de Campos, com focalização em sua produção poética ligada ao movimento de poesia concreta.
A Educomunicação, em diálogo com as tecnologias, na Educação Básica
Authors: Soares Ismar De Oliveira
Published: September 2014

A educomunicação apresenta-se como um paradigma, um conceito orientador de caráter sócio-político-educacional a partir da interface Comunicação/Educação. O fato permite e facilita um diálogo permanente entre os que buscam dar respostas às questões vitais anunciadas e descritas nas diretrizes propostas pelo poder público quanto às “experiências escolares” inovadoras e multidisciplinares, previstas na reforma do ensino básico, em nosso país. Sendo assim, a primeira parte deste artigo está relacionada às diretrizes curriculares nacionais, tanto para o ensino fundamental quanto para o ensino médio, elaboradas ao longo das últimas duas décadas. A segunda parte é dedicada à apresentação dos artigos e autores presentes na atual edição.
Legenden der Jeremia-Exegese (II): Die Verschleppung Jeremias nach Ägypten
Authors: Stipp Hermann-Josef
Published: September 2014

The article examines the widely accepted theory that according to Jer 43:5-7 Jeremiah was forced to emigrate to Egypt by his fellow-countrymen. The scrutiny concludes that the assumption, besides being inherently improbable, not only lacks a textual basis but contradicts important features of the source. Therefore, it ought to be abandoned.
Jeremiah as yhwh’s Stronghold (Jer 1:18)
Authors: Maier Christl M.
Published: September 2014

In the book of Jeremiah, the prophet proclaims that Jerusalem will be destroyed by a foreign nation. According to the call narrative, however, Jeremiah himself is transformed into “a fortified city, an iron pillar, and a bronze wall” (Jer 1:18). While these architectural metaphors have often been explained with regard to Egyptian royal ideology, the article further explores their meaning and function within their literary context. Comparing characterizations of both the prophet and personified Jerusalem, the essay argues that Jer 1:18 offers a late comment to the book: Jeremiah functions as a stand-in for yhwh’s favorite city. A text-critical investigation of Jer 1:18 demonstrates—in contrast to former studies—that the mt pluses deliberately elaborate the prophet’s role by rendering him a substitute for the temple.
“The Wealth of Nations Shall Come to You”: Light, Tribute, and Implacement in Isaiah 60
Authors: Jones Christopher M.
Published: September 2014

I draw on spatial theory, and particularly Edward Casey’s concept of “implacement,” to investigate the rhetoric of Isaiah 60. Implacement means being concretely placed. I argue that Isaiah 60 uses the motifs of light and tribute to “implace” Jerusalem for its audience. It uses these motifs to acknowledge Jerusalem’s degraded state in the early fifth century and to imagine the means by which the city’s restoration will occur. Drawing on Wells’ work on inner-Isaianic allusion and Strawn’s argument that Isa 60 incorporates and subverts Persian iconography, I argue that, in Isa 60, the motif of light implaces Jerusalem by marking it out as the cosmic center and by drawing the nations to the city. The motif of tribute, meanwhile, actually transfers the implacedness of the nations to Jerusalem. The rhetoric of the text encourages its audience to re-imagine the Jerusalem of their experience in its restored and glorified future state.
Causes and Implications of Extreme Atmospheric Moisture Demand during the Record-Breaking 2011 Wildfire Season in the Southwestern United States
Authors: Williams A. Park , Seager Richard , Berkelhammer Max , Macalady Alison K. , Crimmins Michael A. , Swetnam Thomas W. , Trugman Anna T. , Buenning Nikolaus , Hryniw Natalia , McDowell Nate G. , Noone David , Mora Claudia I. , Rahn Thom
Published: September 2014

In 2011, exceptionally low atmospheric moisture content combined with moderately high temperatures to produce a record-high vapor pressure deficit (VPD) in the southwestern United States (SW). These conditions combined with record-low cold-season precipitation to cause widespread drought and extreme wildfires. Although interannual VPD variability is generally dominated by temperature, high VPD in 2011 was also driven by a lack of atmospheric moisture. The May–July 2011 dewpoint in the SW was 4.5 standard deviations below the long-term mean. Lack of atmospheric moisture was promoted by already very dry soils and amplified by a strong ocean-to-continent sea level pressure gradient and upper-level convergence that drove dry northerly winds and subsidence upwind of and over the SW. Subsidence drove divergence of rapid and dry surface winds over the SW, suppressing southerly moisture imports and removing moisture from already dry soils. Model projections developed for the fifth phase of the Coupled Model Intercomparison Project (CMIP5) suggest that by the 2050s warming trends will cause mean warm-season VPD to be comparable to the record-high VPD observed in 2011. CMIP5 projections also suggest increased interannual variability of VPD, independent of trends in background mean levels, as a result of increased variability of dewpoint, temperature, vapor pressure, and saturation vapor pressure. Increased variability in VPD translates to increased probability of 2011-type VPD anomalies, which would be superimposed on ever-greater background VPD levels. Although temperature will continue to be the primary driver of interannual VPD variability, 2011 served as an important reminder that atmospheric moisture content can also drive impactful VPD anomalies.
On the Validity of the β-Plane Approximation in the Dynamics and the Chaotic Advection of a Point Vortex Pair Model on a Rotating Sphere
Authors: Drótos Gábor , Tél Tamás
Published: September 2014

The dynamics of modulated point vortex pairs is investigated on a rotating sphere, where modulation is chosen to reflect the conservation of angular momentum (potential vorticity). In this setting the authors point out a qualitative difference between the full spherical dynamics and the one obtained in a β-plane approximation. In particular, dipole trajectories starting at the same location evolve to completely different directions under these two treatments, despite the fact that the deviations from the initial latitude remain small. This is a strong indication for the mathematical inconsistency of the traditional β-plane approximation. At the same time, a consistently linearized set of equations of motion leads to trajectories agreeing with those obtained under the full spherical treatment. The β-plane advection patterns due to chaotic advection in the velocity field of finite-sized vortex pairs are also found to considerably deviate from those of the full spherical treatment, and quantities characterizing transport properties (e.g., the escape rate from a given region) strongly differ.
Optimal Ranking Regime Analysis of Intra- to Multidecadal U.S. Climate Variability. Part I: Temperature*
Authors: Mauget Steven A. , Cordero Eugene C.
Published: September 2014

The optimal ranking regime (ORR) method was used to identify intradecadal to multidecadal (IMD) time windows containing significant ranking sequences in U.S. climate division temperature data. The simplicity of the ORR procedure’s output—a time series’ most significant nonoverlapping periods of high or low rankings—makes it possible to graphically identify common temporal breakpoints and spatial patterns of IMD variability in the analyses of 102 climate division temperature series. This approach is also applied to annual Atlantic multidecadal oscillation (AMO) and Pacific decadal oscillation (PDO) climate indices, a Northern Hemisphere annual temperature (NHT) series, and divisional annual and seasonal temperature data during 1896–2012. In addition, Pearson correlations are calculated between PDO, AMO, and NHT series and the divisional temperature series. Although PDO phase seems to be an important influence on spring temperatures in the northwestern United States, eastern temperature regimes in annual, winter, summer, and fall temperatures are more coincident with cool and warm phase AMO regimes. Annual AMO values also correlate significantly with summer temperatures along the Eastern Seaboard and fall temperatures in the U.S. Southwest. Given evidence of the abrupt onset of cold winter temperatures in the eastern United States during 1957/58, possible climate mechanisms associated with the cause and duration of the eastern U.S. warming hole period—identified here as a cool temperature regime occurring between the late 1950s and late 1980s—are discussed.
Assessing Community Resilience
Authors: Pfefferbaum Rose L. , Pfefferbaum Betty , Nitiéma Pascal , Houston J. Brian , Van Horn Richard L.
Published: September 2014

This article describes an application of the Communities Advancing Resilience Toolkit Assessment Survey using a sample of affiliated volunteer responders. The Communities Advancing Resilience Toolkit Assessment Survey is a theory-based, evidence-informed instrument. Early applications of the survey identified four domains: Connection and Caring, Resources, Transformative Potential, and Disaster Management. The version of the instrument used in the current application added items related to Information and Communication, thus creating a fifth domain. The application confirmed the five-factor model and the instrument demonstrated good reliability. Affiliated volunteer responders served as key informants regarding community resilience because of their involvement in local disaster readiness and response. Home ownership and active membership in an affiliated volunteer responder group were associated with the total community resilience score and with multiple domain scores, suggesting the importance of community member investment and engagement for a community’s resilience. Although the study sample involved affiliated volunteer responders, it is likely that engagement in other community organizations and activities may yield similar benefits for resilience.
Wartime Institutions
Authors: Arjona Ana
Published: September 2014

Theories of civil war usually theorize the choices of civilians and combatants without considering the institutional context in which they interact. Despite common depictions of war as chaotic and anarchic, order often emerges locally. Institutions vary greatly over time and space and, as in peacetime, shape behavior. In this article, I propose a research agenda on local wartime institutions. To this end, I present original evidence on conflict areas in Colombia to illustrate the scope of variation, propose the concept of wartime social order and a typology, and discuss several ways in which research on wartime institutions can contribute to our study of civil war both at the micro and macro levels.
Transplantation of SHED Prevents Bone Loss in the Early Phase of Ovariectomy-induced Osteoporosis
Authors: Liu Y. , Wang L. , Liu S. , Liu D. , Chen C. , Xu X. , Chen X. , Shi S.
Published: September 2014

Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population, possessing multipotent differentiation capacity and immunomodulatory properties. However, the mechanism by which SHED treat immune diseases is not fully understood. Here we show that systemic transplantation of SHED via the tail vein ameliorates ovariectomy (OVX)-induced osteopenia by reducing T-helper 1 (Th1) and T-helper 17 (Th17) cell numbers in the recipient OVX mice. Mechanistically, SHED transplantation induces activated T-cell apoptosis in OVX mice via Fas ligand (FasL)-mediated Fas pathway activation, leading to up-regulation of regulatory T-cells (Tregs) and down-regulation of Th1 and Th17 cells. This SHED-mediated immunomodulation rescues OVX-induced impairment of bone marrow mesenchymal stem cells (BMMSCs) and activation of osteoclastogenesis, resulting in increased bone mass. In summary, SHED-mediated T-cell apoptosis via a FasL/Fas pathway results in immune tolerance and ameliorates the osteopenia phenotype in OVX mice.
Exploring Teacher Questioning as a Formative Assessment Strategy
Authors: Jiang Yan
Published: September 2014

This study explored teacher questioning as a formative assessment strategy by examining the practices of teachers of English as a Foreign Language in Chinese tertiary institutions. It investigated how teachers deployed questions to stimulate student thinking, uncover students’ current level of learning, and allow responses to inform pedagogic decisions. The research methods were classroom observations and interviews. This paper highlights the practice of one experienced teacher who conducted quality questioning to gauge and facilitate learning. The paper provides practical insights into how questioning can be developed as a formative assessment method and recommends equipping teachers with further knowledge and skills to carry out effective questioning.
University EFL Learners’ Perceptions of Their Autonomous Learning Responsibilities and Abilities
Authors: Abdel Razeq Anwar Ahmad
Published: September 2014

This study investigated the readiness of university students for autonomous learning of English as a foreign language. Data was collected using questionnairs and interviews. The study assessed learners’ readiness for autonomous learning across three dimensions: a) learners’ perceptions of their educational responsibilities; b) learners’ abilities related to autonomous learning and c) the actual autonomous English activities that were practiced by the participants while learning English. The data collected were analyzed quantitatively using the comparisons of means method and the t-test. Data collected through the interviews were analyzed qualitatively using the content analysis procedure. Analysis of the results suggested that as a result of previous educational experiences, the learners dwere habituated by their past educational experiences to place the responsibility for the success or failure of their language acquisition on their teachers. However, the participants reported that they have the ability to learn autonomously if given the opportunity to do so. A t-test showed that in terms of students’ perceptions of their abilities to engage in autonomous learning activities, gender and level of achievement did not play a significant role. Recommendations and implications for training autonomous learners are discussed.
Organizing High Schools for Latina/o Youth Success
Authors: Achinstein Betty , Curry Marnie W. , Ogawa Rodney T. , Athanases Steven Z.
Published: September 2014

This article presents a 2-year critical case study of an urban high school innovating to enhance the academic performance of low-income Latina/o students, highlighting high-leverage practices that promote boundary crossing between school and community. First, we highlight foundational elements of school logic, mission, and community ethos that enabled boundary crossing. Second, we identify a key set of boundary-crossing practices that tap and build community wealth, and forms of capital that are shared, by bringing community into school and fostering youth engagement in community. We also reveal opportunities afforded and complexities arising from boundary crossing between school and community.
New model of piezoelectric accelerometer relative movement modulus
Authors: Ghemari Zine , Saad Salah , Amrouche Abdelwaheb , Lakehal Abdelaziz
Published: September 2014

A piezoelectric accelerometer is the first element of a vibration measurement chain, and its improvement can enhance measurement quality. In this work, a new model of relative movement modulus as a function of measurement error is developed, thus minimizing the measurement error and increasing the measurement precision of the accelerometer. Therefore, a precise relationship between the movement relative frequency and the piezoelectric accelerometer natural frequency is extracted in order to determine a good frequency range relative to the piezoelectric accelerometer. Thus, the failure risk of the resonance phenomenon is minimized and the accelerometer piezoelectric reliability is optimized. The developed model is confirmed and validated by experimental tests. The purpose and the objective of this work is to improve the performance and the design of the accelerometer.