bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Situ Timing Error Predictor-Based Two-Cycle Adaptive Frequency Scaling System on an FPGA
Authors: Dam Minh Tung , Nguyen Van Toan , Lee Jeong-Gun
Published: July 2019

In this paper, a timing error predictor (TEP) for adaptive frequency scaling (AFS) is proposed on a field-programmable gate array (FPGA). The use of TEP-based AFS can minimize large timing margin which is added to a clock cycle time for tolerating process, voltage, and temperature (PVT) variations. On an FPGA, in general, the typical dynamic frequency scaling has used the feature of dynamic frequency synthesis (DFS) in a digital clock manager (DCM). However, it has a long locking time. Moreover, during the DCM reconfiguration for generating a new frequency, the lock signal of the DCM can be lost and it leads to possible glitches or spikes at the output. In this work, a variable-length ring oscillator (VLRO), which employs a high-speed carry chain in an FPGA, is proposed to replace the DCM for changing the frequency within one clock cycle without introducing any glitches. Furthermore, an in-situ TEP, which detects timing errors, is combined with VLRO to further reduce the timing margin of a target system. Our proposed in-situ TEP-based AFS scheme is applied to a [Formula: see text]-bit multiplier and implemented on a Spartan-6 FPGA device (XFC6SLX45). The functional correctness of the TEP is verified under various DC supply voltages and operating frequencies. The experimental results show that the proposed TEP-based AFS system switches the clock frequency correctly within two clock cycles and improves circuit performance up to [Formula: see text] the nominal operating condition by minimizing the timing margin.
Design of a Bio-Inspired Embryonic Cellular Array Based on Bus Structure
Authors: Wang Tao , Cai Jinyan , Meng Yafeng , Lv Meng , Li Zexi
Published: July 2019

There are some shortcomings, such as huge hardware resource consumption, functional differentiation is difficult and limited fault detection coverage, when embryonic cellular array (ECA) is used to design large-scale circuit. In this paper, the structure characteristics and communication method of multicellular organism are analyzed briefly, and a new bio-inspired ECA based on bus structure (BECA) is proposed, besides that the corresponding self-repairing strategy is designed. First, the functional decomposition has been applied in BECA, which uses bus structure to realize internal communication. BECA consists of bus and electronic tissues (ET), which can be used to realize large-scale circuit. C17 circuit in ISCAS85 circuit library is chosen as experiment subject, and experiment simulation results indicate that BECA based on bus structure is suitable for large-scale circuit, and the faults occurred in ET can be repaired effectively. In order to research BECA from the mathematical point of view, the reliability evaluation model of BECA is established, which is based on [Formula: see text]-out-of-[Formula: see text] system reliability model. In addition, the hardware resource consumption model of BECA is established by analyzing the number of metal oxide semiconductor (MOS) transistors that ECA consumed. Based on BECA reliability and hardware resource consumption evaluation model, comparative experiment is studied, and the results indicate that the proposed ECA can improve the reliability of circuit and reduce hardware resource consumption effectively. Therefore, the BECA presented will play an important role in designing large-scale digital circuit with self-repairing ability.
Embeddings of weighted Sobolev spaces and a weighted fourth-order elliptic equation
Authors: Guo Zongming , Wan Fangshu , Wang Liping
Published: July 2019

New embeddings of weighted Sobolev spaces are established. Using such embeddings, we obtain the existence and regularity of positive solutions with Navier boundary value problems for a weighted fourth-order elliptic equation. We also obtain Liouville type results for the related equation. Some problems are still open.
Commutative algebraic monoid structures on affine spaces
Authors: Arzhantsev Ivan , Bragin Sergey , Zaitseva Yulia
Published: July 2019

We study commutative associative polynomial operations [Formula: see text] with unit on the affine space [Formula: see text] over an algebraically closed field of characteristic zero. A classification of such operations is obtained up to dimension 3. Several series of operations are constructed in arbitrary dimension. Also we explore a connection between commutative algebraic monoids on affine spaces and additive actions on toric varieties.
Nonlinear Dynamic Analysis of Fractional Damped Viscoelastic Beams
Authors: Zhang Guoqi , Wu Zhiqiang , Li Yajie
Published: July 2019

The nonlinear dynamical response of a simply supported viscoelastic beam subjected to transverse harmonic excitations is investigated. The constitutive law of the viscoelastic beam is modeled in the fractional derivative Kelvin sense. The mathematical model is derived and discretized to a set of ordinary differential equations by Galerkin approximation method. The steady-state response of a single-mode system is obtained by the averaging method. Numerical results are obtained by an algorithm based on the fractional-order Grünwald–Letnikov definition, and compared with the analytical ones for verification. A parametric study and singularity analysis are carried out to determine the influence of the coefficients of the material’s constitutive equation on the responses. To study the effect of beam length and nonlinear coefficient on the nonlinear dynamic response, a numerical simulation is carried out. The periodic, multiple periodic, and chaotic responses are determined using Poincaré section bifurcation diagrams of the local maximum displacement. The above analysis allows us to optimize parametric design scheme for the viscoelastic beam.
Thermal Performance Curve Analysis for Enhancement of an Air Conditioner in Thailand
Authors: Chaiyat Nattaporn
Published: July 2019

This study presents a method for analysing air conditioner efficiency by using a thermal performance curve. Enhancement techniques consisting of the use of a phase change material (PCM), a vapor compression heat pump (VCHP), ultrasound, drop-in refrigerant, a commercial R-32 air conditioner using ultrasound and a double-storage tank are reported under the weather conditions in Thailand. For the PCM, Rubitherm20 (RT-20) in the forms of a paraffin ball and a plastic pack was selected to cool the return air of the evaporator, which directly caused decreases in power consumption of 7.85% and 5.78%, respectively. The R-123 VCHP was integrated with the air conditioner at the condenser to receive and boost rejected heat to the hot water temperature of 60–70∘C. Ultrasonic wave generators at 42[Formula: see text]kHz frequency were installed at the evaporator to improve heat transfer characteristics and reduce the electrical power usage of the air conditioner by 8%. The R-32 drop-in refrigerant technique was tested in an R-410a air conditioner model. The R-32 unit showed the advantages of a smaller environmental impact and a higher cooling energy efficiency ratio (EER) compared with that of the R-410a unit. Moreover, the commercial R-32 air conditioner and a 40 kHz ultrasonic generator were integrated. The combined unit revealed a higher EER of 7.69% compared with that of the conventional commercial R-32 unit. For a double-storage tank, it was shown that the maximum hot water temperature in the storage tank was approximately 49∘C. The highest effective method to enhance the cooling capacity of air-conditioner is the technique of R-32 air conditioner and ultrasonic wave for increasing the cooling efficiency of 8.54%.
Determinants of skeletal muscle oxygen consumption assessed by near-infrared diffuse correlation spectroscopy during incremental handgrip exercise
Authors: Rosenberry Ryan , Tucker Wesley J. , Haykowsky Mark J. , Trojacek Darian , Chamseddine Houda H. , Arena-Marshall Carrie A. , Zhu Ye , Wang Jing , Kellawan J. Mikhail , Tian Fenghua , Nelson Michael D.
Published: July 2019

Near-infrared diffuse correlation spectroscopy (DCS) is a rapidly evolving optical imaging technique for the assessment of skeletal muscle O2 utilization (mVO2). We compared DCS-derived determinants of mVO2 with conventional measures [blood flow by brachial artery Doppler ultrasound and venous O2 saturation ([Formula: see text])] in eight volunteers at rest and during incremental handgrip exercise. Brachial artery blood flow and DCS-derived blood flow index (BFI) were linearly related (R2 = 0.57) and increased with each workload, whereas [Formula: see text] decreased from 65.3 ± 2.5% (rest) to 39.9 ± 3.0% (light exercise; P < 0.01) with no change thereafter. In contrast, DCS-derived tissue O2 saturation decreased progressively with each incremental stage ( P < 0.01), driven almost entirely by an initial steep rise in deoxyhemoglobin/myoglobin, followed by a linear increase thereafter. Whereas seemingly disparate at first glance, we believe these two approaches provide similar information. Indeed, by plotting the mean convective O2 delivery and diffusive O2 conductance, we show that the initial increase in mVO2 during the transition from rest to exercise was achieved by a greater increase in diffusive O2 conductance versus convective O2 delivery (10-fold vs. 4-fold increase, respectively), explaining the initial decline in [Formula: see text]. In contrast, the increase in mVO2 from light to heavy exercise was achieved by equal increases (1.8-fold) in convective O2 delivery and diffusive O2 conductance, explaining the plateau in [Formula: see text]. That DCS-derived BFI and deoxyhemoglobin/myoglobin (surrogate measure of O2 extraction) share the same general biphasic pattern suggests that both DCS and conventional approaches provide complementary information regarding the determinants of mVO2.

NEW & NOTEWORTHY Near-infrared diffuse correlation spectroscopy (DCS) is an emerging optical imaging technique for quantifying skeletal muscle O2 delivery and utilization at the microvascular level. Here, we show that DCS provides complementary insight into the determinants of muscle O2 consumption across a wide range of exercise intensities, further establishing the utility of DCS.
Local exercise does not prevent the aortic stiffening response to acute prolonged sitting: a randomized crossover trial
Authors: Evans William S. , Stoner Lee , Willey Quentin , Kelsch Elizabeth , Credeur Daniel P. , Hanson Erik D.
Published: July 2019

Prolonged sitting has been shown to promote endothelial dysfunction in the lower legs. Furthermore, it has been reported that simple sitting-interruption strategies, including calf raises, prevent leg endothelial dysfunction. However, it is unclear whether prolonged sitting affects central cardiovascular health, or whether simple sitting-interruption strategies prevent impaired central cardiovascular health. This study sought to answer two questions: in young, healthy adults 1) does prolonged sitting (3 h) lead to increased aortic stiffness, and 2) do intermittent calf raise exercises to prevent pooling prevent aortic stiffening. Twenty young, healthy participants (21.7 ± 2.5 yr, 70% female, 25.5 ± 6.1 kg/m2) were randomized to 3 h of sitting with (CALF) or without (CON) 10 calf raises every 10 min. Aortic stiffening [carotid-femoral pulse wave velocity (PWV)] was measured in the supine position pre- and post-sitting. Venous pooling during sitting was estimated with total hemoglobin (tHB) concentration using near-infrared spectroscopy. There were no condition × time interactions. Following 3 h of sitting, PWV significantly increased (0.30 ± 0.46 m/s, P < 0.001). There was no condition effect for PWV ( P = 0.694), indicating the intermittent calf rises did not preserve central cardiovascular health. tHb was not significantly affected by sitting ( P = 0.446) but was 1.9 μM higher for CON versus CALF ( P = 0.106). Sitting increases aortic stiffness in young, healthy individuals, a process that may be influenced by lower extremity blood pooling. Calf raises, which have been reported to preserve vascular function in the legs, do not appear to provide sufficient stimulus for maintaining central cardiovascular health.

NEW & NOTEWORTHY Although simple strategies, such as fidgeting or calf raises, are sufficient for preserving vascular function in the legs, data from the current study indicate that such strategies are not sufficient for maintaining central cardiovascular health, which is linked to cardiovascular disease.
Computational analysis of airflow dynamics for predicting collapsible sites in the upper airways: machine learning approach
Authors: Yeom Seung Ho , Na Ji Sung , Jung Hwi-Dong , Cho Hyung-Ju , Choi Yoon Jeong , Lee Joon Sang
Published: July 2019

Obstructive sleep apnea (OSA) is a common sleep breathing disorder. With the use of computational fluid dynamics (CFD), this study provides a quantitative standard for accurate diagnosis and effective surgery based on the investigation of the relationship between airway geometry and aerodynamic characteristics. Based on computed tomography data from patients having normal geometry, 4 major geometric parameters were selected and a total of 160 idealized cases were modeled and simulated. We created a predictive model using Gaussian process regression (GPR) through a data set obtained through numerical method. The results demonstrated that the mean accuracy of the overall GPR model was ~72% with respect to the CFD results for the realistic upper airway model. A support vector machine model was also used to identify the degree of OSA symptoms in patients as normal-mild and moderate and severe. We achieved an accuracy of 82.5% with the training data set and an accuracy of 80% with the test data set.

NEW & NOTEWORTHY There have been many studies on the analysis of obstructive sleep apnea (OSA) through computational fluid dynamics and finite element analysis. However, these methods are not useful for practical medical applications because they have limited information for OSA symptom. This study employs the machine learning algorithm to predict flow characteristics quickly and to determine the symptoms of the patient's OSA. The overall Gaussian process regression model's mean accuracy was ~72%, and the accuracy for the classification of OSA was >80%.
Effect of the Domain Geometry on the Solutions to Fractional Brezis-Nirenberg Problem
Authors: Tian Qiaoyu , Xu Yonglin
Published: July 2019

In this paper, we consider the Brezis-Nirenberg problem for the nonlocal fractional elliptic equation Aαux=NN-2αuxp+εux, x∈Ω, ux>0, x∈Ω, u(x)=0, x∈∂Ω, where 0<α<1 is fixed, p=N+2α/N-2α, ε is a small parameter, and Ω is a bounded smooth domain of RN(N≥4α). Aα denotes the fractional Laplace operator defined through the spectral decomposition. Under some geometry hypothesis on the domain Ω, we show that all solutions to this problem are least energy solutions.
Large-Scale Coarse-to-Fine Object Retrieval Ontology and Deep Local Multitask Learning
Authors: Ly Ngoc Q. , Do Tuong K. , Nguyen Binh X.
Published: July 2019

Object retrieval plays an increasingly important role in video surveillance, digital marketing, e-commerce, etc. It is facing challenges such as large-scale datasets, imbalanced data, viewpoint, cluster background, and fine-grained details (attributes). This paper has proposed a model to integrate object ontology, a local multitask deep neural network (local MDNN), and an imbalanced data solver to take advantages and overcome the shortcomings of deep learning network models to improve the performance of the large-scale object retrieval system from the coarse-grained level (categories) to the fine-grained level (attributes). Our proposed coarse-to-fine object retrieval (CFOR) system can be robust and resistant to the challenges listed above. To the best of our knowledge, the new main point of our CFOR system is the power of mutual support of object ontology, a local MDNN, and an imbalanced data solver in a unified system. Object ontology supports the exploitation of the inner-group correlations to improve the system performance in category classification, attribute classification, and conducting training flow and retrieval flow to save computational costs in the training stage and retrieval stage on large-scale datasets, respectively. A local MDNN supports linking object ontology to the raw data, and an imbalanced data solver based on Matthews’ correlation coefficient (MCC) addresses that the imbalance of data has contributed effectively to increasing the quality of object ontology realization without adjusting network architecture and data augmentation. In order to evaluate the performance of the CFOR system, we experimented on the DeepFashion dataset. This paper has shown that our local MDNN framework based on the pretrained NASNet architecture has achieved better performance (14.2% higher in recall rate) compared to single-task learning (STL) in the attribute learning task; it has also shown that our model with an imbalanced data solver has achieved better performance (5.14% higher in recall rate for fewer data attributes) compared to models that do not take this into account. Moreover, MAP@30 hovers 0.815 in retrieval on an average of 35 imbalanced fashion attributes.
Abdominal Wall Clear Cell Carcinoma: Case Report of a Rare Event with Potential Diagnostic Difficulties
Authors: Rivera Rolon Maria del Mar , Allen Dyron , Richardson Gwyn , Clement Cecilia
Published: July 2019

Clear cell carcinoma (CCC) is a well-known aggressive histological type of carcinoma, predominantly seen in ovary and endometrium. However, CCC arising in abdominal wall is a very rare event. We report a case of a 48-year-old woman with an abdominal wall mass at her cesarean section (c-section) scar, which increased in size and became painful in the last months. Radiology revealed a 7 cm mass in the right inferior rectus muscle sheath, suggestive of endometriosis. An irregular, firm mass was resected, densely adherent to the rectus muscle and pubic bone. Frozen section revealed a multicystic lesion with minimal cytologic atypia, and a benign cystic neoplasm was favored. However, permanent sections showed marked nuclear atypia, hobnail morphology, and areas of infiltrative growth within fibrous stroma. No benign endometrial glands were found, although fibrosis and hemorrhage were present. Napsin-A, racemase, and PAX-8 were positive, consistent with CCC, likely arising within a c-section endometriosis focus. Although CCC usually presents with moderate to marked nuclear atypia, it can be mild and, especially in cases with a predominant cystic pattern, create diagnostic difficulties. An endometriosis-associated malignancy should be considered in the differential with any enlarging nodule or increasing pain within an abdominal wall scar.
Shape Optimization and Stability Analysis for Kiewitt Spherical Reticulated Shell of Triangular Pyramid System
Authors: Zhang Le-Wen , Wu Jing , Zhang Da-Liang
Published: July 2019

The Kiewitt spherical reticulated shell of triangular pyramid system is taken as the object of this study; a macroprogram of parametric modeling is developed by using the ANSYS Parametric Design Language. The minimum structural total weight is taken as the objective function, and a shape optimization program is proposed and compiled by adopting the sequence two‐stage algorithm in FORTRAN environment. Then, the eigenvalue buckling analysis for Kiewitt spherical reticulated shell of triangular pyramid system is carried out with the span of 90 m and rise‐span ratio of 1/7~1/3. On this basis, the whole nonlinear buckling process of the structure is researched by considering initial geometrical imperfection. The load‐displacement curves are drawn, and the nonlinear behaviors of special nodes are analyzed. The structural nonlinear behaviors affected by rise‐span ratio are discussed. Finally, the stability of reticulated shell before and after optimization is compared. The research results show that (1) users can easily get the required models only by inputting five parameters, i.e., the shell span (S), rise (F), latitudinal portions (Kn), radial loops (Nx), and thickness (T). (2) Under the conditions of different span and rise‐span ratio, the optimal grid number and bar section for the Kiewitt spherical reticulated shell of triangular pyramid system existed after optimization; i.e., the structural total weight is the lightest. (3) The whole rigidity and stability of the Kiewitt spherical reticulated shell of triangular pyramid system are very nice, and the reticulated shell after optimization can still meet the stability requirement. (4) When conducting the reticulated shell design, the structural stability and carrying capacity can be improved by increasing the rise‐span ratio or the rise. (5) From the perspective of stability, the rise‐span ratio of the Kiewitt spherical reticulated shell of triangular pyramid system should not choose 1/7.
Causal Enzymology and Physiological Aspects May Be Accountable to Membrane Integrity in Response to Salt Stress in Arabidopsis thaliana Lines
Authors: Bouazzi Hassiba , Feki Kaouthar , Zouari Nabil , Sahnoun Mouna , Brini Faical , Saibi Walid
Published: July 2019

Apart from their significance in the protection against stress conditions, the plant cell membranes are essential for proper development of the diverse surface structures formed on aerial plant organs. In addition, we signal that membrane remodeling and integrity are function of some of causal physiological and enzymological aspects such as the MDA, the ion leakage and also the monitoring of some phytozymes involved in lipid and cellulose metabolisms. Those last ones are related to the membrane structure (lipases and cellulases), that were assessed in durum wheat dehydrin transgenic context (YS, K1-K2, DH2, and DH4), proline metabolic mutant (P5CS1-4) per comparison with the wild-type plant (Wt). We report also the docking data reinforcing the fact that the membrane integrity seems to be function of causal enzymological behaviors, through the molecular dynamic investigation resulting from the dehydrin-phytozyme interactions and also from the inhibition effect of the durum wheat LTP4 on the lipase activity.
Recurrent Hematomas following a Revision Total Hip Arthroplasty in Acquired Coagulation Factor XIII Deficiency
Authors: Takashima Yoshinori , Hashimoto Shingo , Kamenaga Tomoyuki , Tsubosaka Masanori , Kuroda Yuichi , Takeuchi Kazuhiro , Takayama Koji , Hayashi Shinya , Kuroda Ryosuke , Matsumoto Tomoyuki
Published: July 2019

Coagulation factor XIII (FXIII) is the final enzyme in the coagulation cascade and plays an important role in catalyzing the intermolecular cross-linking of fibrin polymers. FXIII deficiency is a rare disorder that presents with recurrent soft tissue bleeding. In this case report, we describe a patient with recurrent hematomas, following a revision total hip arthroplasty (THA). A 50-year-old female patient with no past history of bleeding and with a normal perioperative coagulation profile presented with recurrent hip joint hematomas. Her plasma FXIII activity showed a slight decrease (69%). Therefore, the patient was diagnosed with an acquired deficiency and was administered FXIII to correct it. The bleeding did not recur once the FXIII activity had returned to a normal level (76%). At 2 months after the second evacuation procedure, the patient was discharged from the hospital in an ambulatory state. There has been no recurrence of a hematoma since. We managed a rare case of acquired FXIII deficiency, which highlighted that a patient can present with an acquired bleeding disorder despite having a normal coagulation profile. An acquired FXIII deficiency should be suspected in patients with inexplicable, sudden-onset bleeding, as early diagnosis and treatment are important to prevent life-threatening complications.
Weight Lifting Trajectory Optimization for Variable Stiffness Actuated Robot
Authors: Ji Chen , Kong Minxiu , Li Ruifeng
Published: July 2019

Variable stiffness actuator is a new actuation of robot which is inspired by motor control of human arm. And it is promising way to exploit the human‐like performance and human‐like motion. However, due to the mechanical complexity and redundancy of the actuators, it is not trivial to control the variable stiffness actuated robot to perform a human‐like motion. In this paper, the weight lifting problem with variable stiffness actuated robot is studied. Then, the original problem is formulated as a constrained optimal control problem and transformed as a general nonlinear programming problem with Gauss pseudospectral method. Simulation studies demonstrate the effectiveness of the proposed method compared with the iLQR approach. Furthermore, the simulations results are presented to show the influence of stiffness variation of variable stiffness actuators on the weight lifting problem.
A Systematic View Exploring the Role of Chloroplasts in Plant Abiotic Stress Responses
Authors: Yoo Yo-Han , Hong Woo-Jong , Jung Ki-Hong
Published: July 2019

Chloroplasts are intracellular semiautonomous organelles central to photosynthesis and are essential for plant growth and yield. The significance of the function of chloroplast-related genes in response to climate change has not been well studied in crops. In the present study, the initial focus was on genes that were predicted to be located in the chloroplast genome in rice, a model crop plant, with genes either preferentially expressed in the leaf or ubiquitously expressed in all organs. The characteristics were analyzed by Gene Ontology (GO) enrichment and MapMan functional classification tools. It was then identified that 110 GO terms (45 for leaf expression and 65 for ubiquitous expression) and 1,695 genes mapped to MapMan overviews were strongly associated with chloroplasts. In particular, the MapMan cellular response overview revealed a close association between heat stress response and chloroplast-related genes in rice. Moreover, features of these genes in response to abiotic stress were analyzed using a large-scale publicly available transcript dataset. Consequently, the expression of 215 genes was found to be upregulated in response to high temperature stress. Conversely, genes that responded to other stresses were extremely limited. In other words, chloroplast-related genes were found to affect abiotic stress response mainly through high temperature response, with little effect on response to drought and salinity stress. These results suggest that genes involved in diurnal rhythm in the leaves participate in the reaction to recognize temperature changes in the environment. Furthermore, the predicted protein–protein interaction network analysis associated with high temperature stress is expected to provide a very important basis for the study of molecular mechanisms by which chloroplasts will respond to future climate changes.
T Cell-Derived IL-17A Induces Vascular Dysfunction via Perivascular Fibrosis Formation and Dysregulation of⋅NO/cGMP Signaling
Authors: Schüler Rebecca , Efentakis Panagiotis , Wild Johannes , Lagrange Jérémy , Garlapati Venkata , Molitor Michael , Kossmann Sabine , Oelze Matthias , Stamm Paul , Li Huige , Schäfer Katrin , Münzel Thomas , Daiber Andreas , Waisman Ari , Wenzel Philip , Karbach Susanne Helena
Published: July 2019

Aims. The neutrophil recruiting cytokine Interleukin-17A (IL-17A) is a key component in vascular dysfunction and arterial hypertension. Moreover, IL-17A has a central role for the vascular infiltration of myeloid cells into the arterial wall in Angiotensin II-induced vascular inflammation. The intention of our study was to analyze the impact of T cell-derived IL-17A on hypertension, vascular function, and inflammation.Methods and Results. Chronic IL-17A overexpression in T cells (CD4-IL-17Aind/+mice) resulted in elevated reactive oxygen species in the peripheral blood and a significant vascular dysfunction compared to control mice. The vascular dysfunction seen in the CD4-IL-17Aind/+mice was only accompanied by a modest and nonsignificant accumulation of inflammatory cells within the vessel wall. Therefore, infiltrating myeloid cells did not serve as an explanation of the vascular dysfunction seen in a chronic IL-17A-driven mouse model. In addition to vascular dysfunction, CD4-IL-17Aind/+mice displayed vascular fibrosis with highly proliferative fibroblasts. This fibroblast proliferation was induced by exposure to IL-17A as confirmed byin vitroexperiments with primary murine fibroblastic cells. We also found that the⋅NO/cGMP pathway was downregulated in the vasculature of the CD4-IL-17Aind/+mice, while levels of protein tyrosine kinase 2 (PYK2), an oxidative stress-triggered process associated with T cell activation, were upregulated in the perivascular fat tissue (PVAT).Conclusions. Our data demonstrate that T cell-derived IL-17A elicits vascular dysfunction by mediating proliferation of fibroblasts and subsequent vascular fibrosis associated with PYK2 upregulation.
Simulation Study on the Motion of Magnetic Particles in Silicone Rubber‐Based Magnetorheological Elastomers
Authors: Xu Zhiqiang , Wu Heng , Wang Qiuliang , Yi Liyin , Wang Jun
Published: July 2019

Magnetorheological elastomer (MRE) is an intelligent composite material and has been widely used in various fields such as vibration reduction and sensing. MRE has an excellent magnetorheological effect through the chaining of its internal magnetic particles. Current studies on MREs mainly focus on the preparation of materials and characterization of mechanical properties. However, very few studies have been conducted on the mechanism of magnetic particle motion during MRE curing. Based on the silicone rubber‐based MRE, the motion mechanism of magnetic particles during curing was explored through numerical simulation. First, we analyzed the magnetic force and viscous force of magnetic particles in MRE and discussed the equations of motion of magnetic particles under applied magnetic field. Further, we established a uniform magnetic field model through the finite element method and simulated the motion of two magnetic particles under the magnetic field. Finally, we discussed the effects of particle distribution angles, particle radii, applied magnetic field strength, and distance between particles on particle velocity and displacement. The results show that the distance between particles has the greatest influence on the motion of magnetic particles, and the size of the distance between particles will affect the contact time of the particles, thus affecting the chain formation of magnetic particles in the MRE.
Attractor and Vector Structure Analyses of Bursting Oscillation with Sliding Bifurcation in Filippov Systems
Authors: Qu Rui , Li Shaolong
Published: July 2019

The main purpose of this paper is to investigate the mechanism of sliding phenomenon in Filippov (nonsmooth) dynamical systems by attractor analysis and vector analysis. A corresponding simple model based on Chua’s circuit with periodic excitation was introduced as an example. The attractor analysis proposed in our previous work is used to discuss the complicated oscillations of the Filippov system. However, it failed to perfectly explain the sliding phenomena and establish an analytical method of constant voltage control. Therefore, the geometric structure and analytic conditions of sliding bifurcations in the general n‐dimensional piecewise smooth system are discussed in detail by vector structure analysis. The prospects of practical application of this method are also discussed in the end.
Decision‐Feedback Aided Multiple‐Symbol Differential Detection in Two‐Way Relay Transmission
Authors: Wang Chanfei , He Jiai , Chen Haiyan
Published: July 2019

In this paper, noncoherent transmission algorithms are proposed in a two‐way relay transmission (TWRT), where differential space‐time block codes based multiple‐symbol differential detection (MSDD) is performed. Specifically, generalized likelihood ratio test aided MSDD (GLRT‐MSDD) is developed with the exhaustive search in the TWRT. In order to solve the challenging problem of high complexity, the GLRT‐MSDD model is reformulated and a decision‐feedback aided MSDD (DF‐MSDD) model is derived. Furthermore, performance analysis and the simulations confirm that the proposed DF‐MSDD provides solid bit error‐rate performance with a lower complexity than GLRT‐MSDD in the TWRT.
Anthropometrics Analysis of Mental Foramen and Accessory Mental Foramen in Zambian Adult Human Mandibles
Authors: Subramanian Balakrishnan , Anthony Severine N. , Mubbunu Lumamba , Hachombwa Chitinti , Mlawa Majuto S. , Majambo Mudhihiri M. , Sasi Rajab M.
Published: July 2019

The mental foramen (MF) and accessory mental foramen (AMF) are the strategically important landmarks during surgical interventions and anaesthetic nerve blocks procedures involving the mental nerve. The study aimed at evaluating anthropometrics of MF and AMF in Zambian adult human mandibles and it was cleared for ethics from TDRC Ethics Review Committee (Reg. No.: 00002911; FWA: 00003729). A total of 33 Zambian adult human mandibles were evaluated for shape, position, and direction of opening of foramen. All measurements were performed using a Digital Vernier Calliper and statistically analysed for per cent frequency and mean and standard deviations, and we performed the one sample t-test for comparative analysis. Data were considered significant at p<0.05. All mandibles that were examined had bilateral MF while unilateral AMF was found in two mandibles (6%). The foramens were mostly oval in shape and their most common position was between the second premolar and first molar and the most common orientation was posterior-superior. The comparative analysis of mandibular anthropometrics showed significant variations (p<0.05) with different ethnic groups. The findings emphasize the ethnic variations and edify that the foramen position is not always as stated in reference textbooks. The clinical creditability of the study is cautioning the surgeons on possible variations of the MF and AMF anthropometrics compared to existing literature in order to avoid any unforeseen injury related to anaesthesia or dental surgeries. Further studies with large sample sizes representing whole country are recommended to establish the standard MF and AMF anthropometrics of Zambian population.
Investigation of Interaction Solutions for Modified Korteweg‐de Vries Equation by Consistent Riccati Expansion Method
Authors: Liang Jin-Fu , Wang Xun
Published: July 2019

A consistent Riccati expansion (CRE) method is proposed for obtaining interaction solutions to the modified Korteweg‐de Vries (mKdV) equation. Using the CRE method, it is shown that interaction solutions such as the soliton‐tangent (or soliton‐cotangent) wave cannot be constructed for the mKdV equation. More importantly, exact soliton‐cnoidal periodic wave interaction solutions are presented. While soliton‐cnoidal interaction solutions were found to degenerate to special resonant soliton solutions for the values of modulus (n) closer to one (upper bound of modulus) in the Jacobi elliptic function, a normal kink‐shaped soliton was observed for values of n closer to zero (lower bound).
Optimal Ordering Strategy for Goods at Multiple Retail Prices under Simultaneous Sales
Authors: Mu Yunzhi , Meng Zhiqing , Shen Rui , Zhou Gengui , Xu Leiyan , Zheng Minchao
Published: July 2019

To stimulate purchases from consumers, retailers nowadays use the multiple retail prices strategy (MRPS), i.e., selling the products at multiple prices simultaneously. The paper extends the current newsboy model and proposes an optimal ordering model for MRPS corresponding to uncertain consumer demands. The Lagrangian multiplier method is applied to solve the problem, and an algorithm for finding the approximate optimal total order quantity is designed. Numerical results show that MRPS is better than the single retail price strategy (SRPS). It further reveals that when there is an order quantity constraint, the retailer needs to control the number of retail prices; that is, retailer’s MRPS is affected by order quantity constraint; sensitivity analysis demonstrates that MRPS is also affected by the price discount coefficient in the case of no order quantity constraint while it is not affected by demand volatility. The research work provides some useful managerial inspirations for retailers.
Using the Cloud‐Bayesian Network in Environmental Assessment of Offshore Wind‐Farm Siting
Authors: Li Ming , Liu Kefeng , Zhang Ren , Hong Mei , Pan Qin
Published: July 2019

Offshore wind energy has become the fastest growing form of renewable energy for the last few years. And the development of offshore wind farms (OWFs) is now characterized by a boom. OWF siting is crucial in the success of wind energy projects. Therefore, this paper aims to introduce intelligent algorithms to improve the siting assessment under conditions of multisource and uncertain information. An optimization macrositing model based on Cloud‐Bayesian Network (Cloud‐BN) is put forward. We introduce the cloud model and adaptive Gaussian cloud transformation (A‐GCT) algorithm to grade indicators and apply BN to achieve nonlinear integration and inference of multi‐indicators. Combined with the fuzzy representation of the cloud model and probabilistic reasoning of BN, the proposed model can investigate the most efficient siting areas of OWFs in the North Sea of Europe. The experimental results indicate that the siting accuracy is up to 86.67% with reference to the actual OWF location.
Effect of Gurney Flap Geometry on a S809 Airfoil
Authors: Hao Li-Shu , Gao Yong-Wei
Published: July 2019

In this paper, the effect of Gurney flap shapes on wind turbine blade airfoil S809 has been studied by numerical simulation. First, the O-type grid is used in the numerical simulation. By comparing with experimental data, such as the lift force, the drag coefficient, and the pressure distribution, the accuracy of the simulation method is validated. Second, the research on the widths of three kinds of rectangular Gurney flaps at the trailing edge of the S809 airfoil is carried out. Rectangular Gurney flaps can considerably increase the lift in both the linear and nonlinear sections, and the maximum lift coefficient can be increased by 20.65%. In addition, the drag and the pitching moment are increased. However, the width of the rectangular Gurney flap has a small impact on the lift, the drag, and the pitching moment. Finally, the effects of rectangular and triangular Gurney flaps on the aerodynamic characteristics of the S809 airfoil are compared. The results show that the triangular flaps can obtain an increase of maximum lift coefficient by 28.42%, which is better than 16.31% of the rectangular flaps.
BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail
Authors: Qin Zhong-yi , Wang Tao , Su Siyuan , Shen Li-ting , Zhu Guang-xi , Liu Qin , Zhang Liang , Liu Ke-wei , Zhang Yue , Zhou Zhi-hua , Zhang Xiao-ning , Wen Liang-zhi , Yao Yue-liang , Sun Wen-jing , Guo Yan , Liu Kai-jun , Liu Lei , Wang Xing-wei , Wei Yan-ling , Wang Jun , Xiao Hua-liang , Liu Pengda , Bian Xiu-wu , Chen Dong-feng , Wang Bin
Published: July 2019

Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells in vitro and their dissemination at distal organs in vivo. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and β-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors.

Significance:

These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors.
Dose Optimization for Anticancer Drug Combinations: Maximizing Therapeutic Index via Clinical Exposure-Toxicity/Preclinical Exposure-Efficacy Modeling
Authors: Bottino Dean C. , Patel Mayankbhai , Kadakia Ekta , Zhou Jilai , Patel Chirag , Neuwirth Rachel , Iartchouk Natasha , Brake Rachael , Venkatakrishnan Karthik , Chakravarty Arijit
Published: July 2019

Purpose:

Recommended phase II dose (RP2D) determination for combination therapy regimens is a constrained optimization problem of maximizing antitumor activity within the constraint of clinical tolerability to provide a wide therapeutic index. A methodology for addressing this problem was developed and tested using clinical and preclinical data from combinations of the investigational drugs TAK-117, a PI3Kα inhibitor, and TAK-228, a TORC1/2 dual inhibitor.

Experimental Design:

Utilizing free fraction-corrected average concentrations, C_{117}^{avg}\ and C_{228}^{avg}, which are the primary pharmacokinetic predictors of single-agent preclinical antitumor activity, a preclinical exposure-efficacy surface was characterized, allowing for nonlinear interactions between growth rate inhibition of the agents on a MDA-MB-361 cell line xenograft model. Logistic regression was used to generate an exposure-effect surface for C_{117}^{avg}\ and C_{228}^{avg} versus clinical toxicity outcomes [experiencing a dose-limiting toxicity (DLT)] in single-agent and combination dose-escalation studies. A maximum tolerated exposure curve was defined at which DLT probability was 25%; predicted antitumor activity along this curve was used to determine optimal RP2D.

Results:

The toxicity constraint curve determined from early clinical data predicted that any clinically tolerable combination was unlikely to result in greater antitumor activity than either single-agent TAK-117 or TAK-228 administered at their respective MTDs. Similar results were obtained with 10 other cell lines, with one agent or the other predicted to outperform the combination.

Conclusions:

This methodology represents a general, principled way of evaluating and selecting optimal RP2D combinations in oncology. The methodology will be retested upon availability of clinical data from TAK-117/TAK-228 combination phase II studies.

See related commentary by Mayawala et al., p. 6564
Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia
Authors: Ma Jun , Zhao Shoujing , Qiao Xinan , Knight Tristan , Edwards Holly , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , White Kathryn , Wang Guan , Zhao Lijing , Lin Hai , Wang Yue , Taub Jeffrey W. , Ge Yubin
Published: July 2019

Purpose:

To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism.

Experimental Design:

Using both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11–derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell death induced by midostaurin or gilteritinib with venetoclax. Changes of Mcl-1 transcript levels were assessed by RT-PCR.

Results:

The combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in “free” Bim, leading to synergistic induction of apoptosis. In vivo results show that gilteritinib in combination with venetoclax has therapeutic potential.

Conclusions:

Inhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML.

See related commentary by Perl, p. 6567
Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Colorectal Cancer: Implications for Response and Resistance to Targeted Therapeutics
Authors: Choi In Sil , Kato Shumei , Fanta Paul T. , Leichman Lawrence , Okamura Ryosuke , Raymond Victoria M. , Lanman Richard B. , Lippman Scott M. , Kurzrock Razelle
Published: July 2019

Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide variants (54–73 genes) and selected copy-number variants, fusions, and indels. Overall, 63 patients [80.8% (63/78)] harbored ctDNA alterations; 59 [75.6% (59/78)], ≥1 characterized alteration (variants of unknown significance excluded). All 59 patients had actionable alterations potentially targetable with FDA-approved drugs [on-label and/or off-label (N = 54) or with experimental drugs in clinical trials (additional five patients); University of California San Diego Molecular Tumor Board assessment]: 45, by OncoKB (http://oncokb.org/#/). The tissue and blood concordance rates for common specific alterations ranged from 62.3% to 86.9% (median = 5 months between tests). In serial samples from patients on anti-EGFR therapy, multiple emerging alterations in genes known to be involved in therapeutic resistance, including KRAS, NRAS, BRAF, EGFR, ERBB2, and MET were detected. In conclusion, over 80% of patients with stage IV colorectal cancer had detectable ctDNA, and the majority had potentially actionable alterations. Concordance between tissue and blood was between 62% and 87%, despite a median of 5 months between tests. Resistance alterations emerged on anti-EGFR therapy. Therefore, biopsy-free, noninvasive ctDNA analysis provides data relevant to the clinical setting. Importantly, sequential ctDNA analysis detects patterns of emerging resistance allowing for precision planning of future therapy.