bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Capacity Constraints Constrain Coalitions?
Authors: Feldman Michal , Geri Ofir
Published: October 2016

We study strong equilibria in symmetric capacitated cost-sharing connection games. In these games, a graph with designated source
s
and sink
t
is given, and each edge is associated with some cost. Each agent chooses strategically an
s
-
t
path, knowing that the cost of each edge is shared equally between all agents using it. Two settings of cost-sharing connection games have been previously studied: (i) games where
coalitions
can form, and (ii) games where edges are associated with
capacities
; both settings are inspired by real-life scenarios. In this work we combine these scenarios and analyze strong equilibria (profiles where no coalition can deviate) in capacitated games. This combination gives rise to new phenomena that do not occur in the previous settings. Our contribution is twofold. First, we provide a topological characterization of networks that always admit a strong equilibrium. Second, we establish tight bounds on the efficiency loss that may be incurred due to strategic behavior, as quantified by the strong price of anarchy (and stability) measures. Interestingly, our results qualitatively differ from those obtained in the analysis of each scenario alone, and the combination of coalitions and capacities entails the introduction of more refined topology classes than previously studied.
Computing Dominance-Based Solution Concepts
Authors: Brandt Felix , Brill Markus
Published: October 2016

Two common criticisms of Nash equilibrium are its dependence on very demanding epistemic assumptions and its computational intractability. We study the computational properties of less demanding set-valued solution concepts that are based on varying notions of dominance. These concepts are intuitively appealing, always exist, and admit unique minimal solutions in important subclasses of games. Examples include Shapley’s saddles, Harsanyi and Selten’s primitive formations, Basu and Weibull’s CURB sets, and Dutta and Laslier’s minimal covering set. Based on a unifying framework proposed by Duggan and Le Breton, we formulate two generic algorithms for computing these concepts and investigate for which classes of games and which properties of the underlying dominance notion the algorithms are sound and efficient. We identify two sets of conditions that are sufficient for polynomial-time computability and show that the conditions are satisfied, for instance, by saddles and primitive formations in normal-form games, minimal CURB sets in two-player games, and the minimal covering set in symmetric matrix games. Our positive algorithmic results explain regularities observed in the literature, but also apply to several solution concepts whose computational complexity was previously unknown.
Automated Quality Assessment of Metadata across Open Data Portals
Authors: Neumaier Sebastian , Umbrich Jürgen , Polleres Axel
Published: October 2016

The Open Data movement has become a driver for publicly available data on the Web. More and more data—from governments and public institutions but also from the private sector—are made available online and are mainly published in so-called Open Data portals. However, with the increasing number of published resources, there is a number of concerns with regards to the quality of the data sources and the corresponding metadata, which compromise the searchability, discoverability, and usability of resources.

In order to get a more complete picture of the severity of these issues, the present work aims at developing a generic metadata quality assessment framework for various Open Data portals: We treat data portals independently from the portal software frameworks by mapping the specific metadata of three widely used portal software frameworks (CKAN, Socrata, OpenDataSoft) to the standardized Data Catalog Vocabulary metadata schema. We subsequently define several quality metrics, which can be evaluated automatically and in an efficient manner. Finally, we report findings based on monitoring a set of over 260 Open Data portals with 1.1M datasets. This includes the discussion of general quality issues, for example, the retrievability of data, and the analysis of our specific quality metrics.
Adaptive Optimization Modeling of Preconditioned Conjugate Gradient on Multi-GPUs
Authors: Gao Jiaquan , Wang Yu , Wang Jun , Liang Ronghua
Published: October 2016

The preconditioned conjugate gradient (PCG) algorithm is a well-known iterative method for solving sparse linear systems in scientific computations. GPU-accelerated PCG algorithms for large-sized problems have attracted considerable attention recently. However, on a specific multi-GPU platform, producing a highly parallel PCG implementation for any large-sized problem requires significant time because several manual steps are involved in adjusting the related parameters and selecting an appropriate storage format for the matrix block that is assigned to each GPU. This motivates us to propose adaptive optimization modeling of PCG on multi-GPUs, which mainly involves the following parts: (1) an optimization multi-GPU parallel framework of PCG and (2) the profile-based optimization modeling for each one of the main components of the PCG algorithm, including vector operation, inner product, and sparse matrix-vector multiplication (SpMV). Our model does not construct a new storage format or kernel but automatically and rapidly generates an optimal parallel PCG algorithm for any problem on a specific multi-GPU platform by integrating existing storage formats and kernels. We take a vector operation kernel, an inner-product kernel, and five popular SpMV kernels for an example to present the idea of constructing the model. Given that our model is general, independent of the problems, and dependent on the resources of devices, this model is constructed only once for each type of GPU. The experiments validate the high efficiency of our proposed model.
A Cross-Platform SpMV Framework on Many-Core Architectures
Authors: Zhang Yunquan , Li Shigang , Yan Shengen , Zhou Huiyang
Published: October 2016

Sparse Matrix-Vector multiplication (SpMV) is a key operation in engineering and scientific computing. Although the previous work has shown impressive progress in optimizing SpMV on many-core architectures, load imbalance and high memory bandwidth remain the critical performance bottlenecks. We present our novel solutions to these problems, for both GPUs and Intel MIC many-core architectures. First, we devise a new SpMV format, called Blocked Compressed Common Coordinate (BCCOO). BCCOO extends the blocked Common Coordinate (COO) by using bit flags to store the row indices to alleviate the bandwidth problem. We further improve this format by partitioning the matrix into vertical slices for better data locality. Then, to address the load imbalance problem, we propose a highly efficient matrix-based segmented sum/scan algorithm for SpMV, which eliminates global synchronization. At last, we introduce an autotuning framework to choose optimization parameters. Experimental results show that our proposed framework has a significant advantage over the existing SpMV libraries. In single precision, our proposed scheme outperforms clSpMV COCKTAIL format by 255% on average on AMD FirePro W8000, and outperforms CUSPARSE V7.0 by 73.7% on average and outperforms CSR5 by 53.6% on average on GeForce Titan X; in double precision, our proposed scheme outperforms CUSPARSE V7.0 by 34.0% on average and outperforms CSR5 by 16.2% on average on Tesla K20, and has equivalent performance compared with CSR5 on Intel MIC.
AIM
Authors: Ahn Junwhan , Yoo Sungjoo , Choi Kiyoung
Published: October 2016

In this article, we propose Aggregation-in-Memory (AIM), a new processing-in-memory system designed for energy efficiency and near-term adoption. In order to efficiently perform aggregation, we implement simple aggregation operations in main memory and develop a locality-adaptive host architecture for in-memory aggregation, called cache-conscious aggregation. Through this, AIM executes aggregation at the most energy-efficient location among all levels of the memory hierarchy. Moreover, AIM minimally changes existing sequential programming models and provides fully automated compiler toolchain, thereby allowing unmodified legacy software to use AIM. Evaluations show that AIM greatly improves the energy efficiency of main memory and the system performance.
Digital Lollipop
Authors: Ranasinghe Nimesha , Do Ellen Yi-Luen
Published: October 2016

Among the five primary senses, the sense of taste is the least explored as a form of digital media applied in Human--Computer Interface. This article presents an experimental instrument, the Digital Lollipop, for digitally simulating the sensation of taste (gustation) by utilizing electrical stimulation on the human tongue. The system is capable of manipulating the properties of electric currents (magnitude, frequency, and polarity) to formulate different stimuli. To evaluate the effectiveness of this method, the system was experimentally tested in two studies. The first experiment was conducted using separate regions of the human tongue to record occurrences of basic taste sensations and their respective intensity levels. The results indicate occurrences of sour, salty, bitter, and sweet sensations from different regions of the tongue. One of the major discoveries of this experiment was that the sweet taste emerges via an inverse-current mechanism, which deserves further research in the future. The second study was conducted to compare natural and artificial (virtual) sour taste sensations and examine the possibility of effectively controlling the artificial sour taste at three intensity levels (mild, medium, and strong). The proposed method is attractive since it does not require any chemical solutions and facilitates further research opportunities in several directions including human--computer interaction, virtual reality, food and beverage, as well as medicine.
Fixation Prediction through Multimodal Analysis
Authors: Min Xiongkuo , Zhai Guangtao , Gu Ke , Yang Xiaokang
Published: October 2016

In this article, we propose to predict human eye fixation through incorporating both audio and visual cues. Traditional visual attention models generally make the utmost of stimuli’s visual features, yet they bypass all audio information. In the real world, however, we not only direct our gaze according to visual saliency, but also are attracted by salient audio cues. Psychological experiments show that audio has an influence on visual attention, and subjects tend to be attracted by the sound sources. Therefore, we propose fusing both audio and visual information to predict eye fixation. In our proposed framework, we first localize the moving--sound-generating objects through multimodal analysis and generate an audio attention map. Then, we calculate the spatial and temporal attention maps using the visual modality. Finally, the audio, spatial, and temporal attention maps are fused to generate the final audiovisual saliency map. The proposed method is applicable to scenes containing moving--sound-generating objects. We gather a set of video sequences and collect eye-tracking data under an audiovisual test condition. Experiment results show that we can achieve better eye fixation prediction performance when taking both audio and visual cues into consideration, especially in some typical scenes in which object motion and audio are highly correlated.
Presleep protein ingestion does not compromise the muscle protein synthetic response to protein ingested the following morning
Authors: Wall Benjamin T. , Burd Nicholas A. , Franssen Rinske , Gorissen Stefan H. M. , Snijders Tim , Senden Joan M. , Gijsen Annemie P. , van Loon Luc J. C.
Published: October 2016

Protein ingestion before sleep augments postexercise muscle protein synthesis during overnight recovery. It is unknown whether postexercise and presleep protein consumption modulates postprandial protein handling and myofibrillar protein synthetic responses the following morning. Sixteen healthy young (24 ± 1 yr) men performed unilateral resistance-type exercise (contralateral leg acting as a resting control) at 2000. Participants ingested 20 g of protein immediately after exercise plus 60 g of protein presleep (PRO group; n = 8) or equivalent boluses of carbohydrate (CON; n = 8). The subsequent morning participants received primed, continuous infusions of l-[ ring-2H5]phenylalanine and l-[1-13C]leucine combined with ingestion of 20 g intrinsically l-[1-13C]phenylalanine- and l-[1-13C]leucine-labeled protein to assess postprandial protein handling and myofibrillar protein synthesis in the rested and exercised leg in CON and PRO. Exercise increased postabsorptive myofibrillar protein synthesis rates the subsequent day ( P < 0.001), with no differences between CON and PRO. Protein ingested in the morning increased myofibrillar protein synthesis in both the exercised and rested leg ( P < 0.01), with no differences between treatments. Myofibrillar protein bound l-[1-13C]phenylalanine enrichments were greater in the exercised (0.016 ± 0.002 and 0.015 ± 0.002 MPE in CON and PRO, respectively) vs. rested (0.010 ± 0.002 and 0.009 ± 0.002 MPE in CON and PRO, respectively) leg ( P < 0.05), with no differences between treatments ( P > 0.05). The additive effects of resistance-type exercise and protein ingestion on myofibrillar protein synthesis persist for more than 12 h after exercise and are not modulated by protein consumption during acute postexercise recovery. This work provides evidence of an extended window of opportunity where presleep protein supplementation can be an effective nutrient timing strategy to optimize skeletal muscle reconditioning.
Crucial roles of nitric oxide synthases in β-adrenoceptor-mediated bladder relaxation in mice
Authors: Satake Yohei , Satoh Kimio , Nogi Masamichi , Omura Junichi , Godo Shigeo , Miyata Satoshi , Saito Hiroki , Tanaka Shuhei , Ikumi Yosuke , Yamashita Shinichi , Kaiho Yasuhiro , Tsutsui Masato , Arai Yoichi , Shimokawa Hiroaki
Published: October 2016

The specific roles of nitric oxide (NO) synthases (NOSs) in bladder smooth muscle remain to be elucidated. We examined the roles of NOSs in β-adrenoceptor (AR)-mediated bladder relaxation. Male mice (C57BL6) deficient of neuronal NOS [nNOS-knockout (KO)], endothelial NOS (eNOS-KO), neuronal/endothelial NOS (n/eNOS-KO), neuronal/endothelial/inducible NOS (n/e/iNOS-KO), and their controls [wild-type (WT)] were used. Immunohistochemical analysis was performed in the bladder. Then the responses to relaxing agents and the effects of several inhibitors on the relaxing responses were examined in bladder strips precontracted with carbachol. Immunofluorescence staining showed expressions of nNOS and eNOS in the urothelium and smooth muscle of the bladder. Isoproterenol-induced relaxations were significantly reduced in nNOS-KO mice and were further reduced in n/eNOS-KO and n/e/iNOS-KO mice compared with WT mice. The relaxation in n/e/iNOS-KO mice was almost the same as in n/eNOS-KO mice. Inhibition of Ca2+-activated K+ (KCa) channel with charybdotoxin and apamin abolished isoproterenol-induced bladder relaxation in WT mice. Moreover, direct activation of KCa channel with NS1619 caused comparable extent of relaxations among WT, nNOS-KO, and n/eNOS-KO mice. In contrast, NONOate (a NO donor) or hydrogen peroxide (H2O2) (another possible relaxing factor from eNOS) caused minimal relaxations, and catalase (H2O2 scavenger) had no inhibitory effects on isoproterenol-induced relaxations. These results indicate that both nNOS and eNOS are substantially involved in β-AR-mediated bladder relaxations in a NO- or H2O2-independent manner through activation of KCa channels.
Rapid and lasting enhancement of dopaminergic modulation at the hippocampal mossy fiber synapse by electroconvulsive treatment
Authors: Kobayashi Katsunori , Imoto Yuki , Yamamoto Fumi , Kawasaki Mayu , Ueno Miyuki , Segi-Nishida Eri , Suzuki Hidenori
Published: October 2016

Electroconvulsive therapy (ECT) is an established effective treatment for medication-resistant depression with the rapid onset of action. However, its cellular mechanism of action has not been revealed. We have previously shown that chronic antidepressant drug treatments enhance dopamine D1-like receptor-dependent synaptic potentiation at the hippocampal mossy fiber (MF)-CA3 excitatory synapse. In this study we show that ECT-like treatments in mice also have marked effects on the dopaminergic synaptic modulation. Repeated electroconvulsive stimulation (ECS), an animal model of ECT, strongly enhanced the dopamine-induced synaptic potentiation at the MF synapse in hippocampal slices. Significant enhancement was detectable after the second ECS, and further repetition of ECS up to 11 times monotonously increased the magnitude of enhancement. After repeated ECS, the dopamine-induced synaptic potentiation remained enhanced for more than 4 wk. These synaptic effects of ECS were accompanied by increased expression of the dopamine D1 receptor gene. Our results demonstrate that robust neuronal activation by ECS induces rapid and long-lasting enhancement of dopamine-induced synaptic potentiation at the MF synapse, likely via increased expression of the D1 receptor, at least in part. This rapid enhancement of dopamine-induced potentiation at the excitatory synapse may be relevant to the fast-acting antidepressant effect of ECT.

NEW & NOTEWORTHY We show that electroconvulsive therapy (ECT)-like stimulation greatly enhances synaptic potentiation induced by dopamine at the excitatory synapse formed by the hippocampal mossy fiber in mice. The effect of ECT-like stimulation on the dopaminergic modulation was rapidly induced, maintained for more than 4 wk after repeated treatments, and most likely mediated by increased expression of the dopamine D1 receptor. These effects may be relevant to fast-acting strong antidepressant action of ECT.
Adaptive Multiscale Noise Control Enhanced Stochastic Resonance Method Based on Modified EEMD with Its Application in Bearing Fault Diagnosis
Authors: Li Jimeng , Zhang Jinfeng
Published: October 2016

The structure of mechanical equipment becomes increasingly complex, and tough environments under which it works often make bearings and gears subject to failure. However, effective extraction of useful feature information submerged in strong noise that is indicative of structural defects has remained a major challenge. Therefore, an adaptive multiscale noise control enhanced stochastic resonance (SR) method based on modified ensemble empirical mode decomposition (EEMD) for mechanical fault diagnosis is proposed in the paper. According to the oscillation characteristics of signal itself, the algorithm of modified EEMD can adaptively decompose the fault signals into different scales and it reduces the decomposition levels to improve calculation efficiency of the proposed method. Through filter processing with the constructed filters, the orthogonality of adjacent intrinsic mode functions (IMFs) can be improved, which is conducive to enhancing the extraction of weak features from strong noise. The constructed signal obtained by using IMFs is inputted into the SR system, and the noise control parameter of different scales is optimized and selected with the help of the genetic algorithm, thus achieving the enhancement extraction of weak features. Finally, simulation experiments and engineering application of bearing fault diagnosis demonstrate the effectiveness and feasibility of the proposed method.
Intra‐Articular Hyaluronic Acid Compared to Traditional Conservative Treatment in Dogs with Osteoarthritis Associated with Hip Dysplasia
Authors: Carapeba Gabriel O. L. , Cavaleti Poliana , Nicácio Gabriel M. , Brinholi Rejane B. , Giuffrida Rogério , Cassu Renata N.
Published: October 2016

The purpose of this study was to compare the efficacy of the intra‐articular (IA) hyaluronic acid injection to traditional conservative treatment (TCT) in dogs with osteoarthritis (OA) induced by hip dysplasia. Sixteen dogs were distributed into two groups: Hyal: IA injection of hyaluronic acid (5–10 mg), and Control: IA injection with saline solution (0.5–1.0 mL) in combination with a TCT using an oral nutraceutical (750–1000 mg every 12 h for 90 days) and carprofen (2.2 mg/kg every 12 h for 15 days). All dogs were assessed by a veterinarian on five occasions and the owner completed an assessment form (HCPI and CPBI) at the same time. The data were analyzed using unpaired t test, ANOVA, and Tukey’s test (P < 0.05). Compared with baseline, lower scores were observed in both groups over the 90 days in the veterinarian evaluation, HCPI, and CPBI (P < 0.001). The Hyal group exhibited lower scores from 15 to 90 and 60 to 90 days, in the CBPI and in the veterinarian evaluation, respectively, compared to the Control group. Both treatments reduced the clinical signs associated with hip OA. However, more significant results were achieved with intra‐articular hyaluronic acid injection.
Yoga for Risk Reduction of Metabolic Syndrome: Patient‐Reported Outcomes from a Randomized Controlled Pilot Study
Authors: Sohl Stephanie J. , Wallston Kenneth A. , Watkins Keiana , Birdee Gurjeet S.
Published: October 2016

Lifestyle change is recommended as treatment for adults at risk for metabolic syndrome (MetS), although adoption of new behavioral patterns is limited. In addition, most existing lifestyle interventions do not address psychological stress or quality of life, both of which impact the burden of MetS. Yoga, a form of physical activity that incorporates psychological components (e.g., maintaining attention, relaxation), is a promising intervention for improving the burden of MetS. This randomized controlled trial assessed the feasibility and preliminary efficacy of a 12‐week yoga program coupled with an evidence‐based health education program (HED) compared to HED alone. A secondary, exploratory aim examined perceived stress, quality of life, and related psychological outcomes (mindfulness, perceived health competence, and mood). Sixty‐seven adults at risk for MetS enrolled (mean age [SD]: 58 [10] years; 50% male; 79% non‐Hispanic White). Preliminary results revealed significantly larger improvements in two quality of life domains (role‐physical and general health perceptions) in the HED plus yoga group versus HED alone (ps < 0.05). This is the first study that implemented lifestyle education along with yoga to evaluate the potential unique effects of yoga on participants at risk for MetS. A larger clinical trial is warranted to further investigate these promising patient‐reported outcomes.
A Novel Simulator of Nonstationary Random MIMO Channels in Rayleigh Fading Scenarios
Authors: Zhu Qiuming , Liu Xinglin , Yin Xuefeng , Chen Xiaomin , Xue Cuiwei
Published: October 2016

For simulations of nonstationary multiple-input multiple-output (MIMO) Rayleigh fading channels in time-variant scattering environments, a novel channel simulator is proposed based on the superposition of chirp signals. This new method has the advantages of low complexity and implementation simplicity as the sum of sinusoids (SOS) method. In order to reproduce realistic time varying statistics for dynamic channels, an efficient parameter computation method is also proposed for updating the frequency parameters of employed chirp signals. Simulation results indicate that the proposed simulator is effective in generating nonstationary MIMO channels with close approximation of the time-variant statistical characteristics in accordance with the expected theoretical counterparts.
Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-Like Synoviocytes
Authors: Kong Qing-Zhu , Guo Li-Tao , Yang Jia-Ning , Wang Yan-Fei , Zhao Jing-Xin , Kong Su-Hong , Zhang Meng , Yan Shi , Jin Yu
Published: October 2016

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factorβ-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.
An Analytical Approach for Fast Recovery of the LSI Properties in Magnetic Particle Imaging
Authors: Jabbari Asl Hamed , Yoon Jungwon
Published: October 2016

Linearity and shift invariance (LSI) characteristics of magnetic particle imaging (MPI) are important properties for quantitative medical diagnosis applications. The MPI image equations have been theoretically shown to exhibit LSI; however, in practice, the necessary filtering action removes the first harmonic information, which destroys the LSI characteristics. This lost information can be constant in the x-space reconstruction method. Available recovery algorithms, which are based on signal matching of multiple partial field of views (pFOVs), require much processing time and a priori information at the start of imaging. In this paper, a fast analytical recovery algorithm is proposed to restore the LSI properties of the x-space MPI images, representable as an image of discrete concentrations of magnetic material. The method utilizes the one-dimensional (1D) x-space imaging kernel and properties of the image and lost image equations. The approach does not require overlapping of pFOVs, and its complexity depends only on a small-sized system of linear equations; therefore, it can reduce the processing time. Moreover, the algorithm only needs a priori information which can be obtained at one imaging process. Considering different particle distributions, several simulations are conducted, and results of 1D and 2D imaging demonstrate the effectiveness of the proposed approach.
Exploring Deep Learning and Transfer Learning for Colonic Polyp Classification
Authors: Ribeiro Eduardo , Uhl Andreas , Wimmer Georg , Häfner Michael
Published: October 2016

Recently, Deep Learning, especially through Convolutional Neural Networks (CNNs) has been widely used to enable the extraction of highly representative features. This is done among the network layers by filtering, selecting, and using these features in the last fully connected layers for pattern classification. However, CNN training for automated endoscopic image classification still provides a challenge due to the lack of large and publicly available annotated databases. In this work we explore Deep Learning for the automated classification of colonic polyps using different configurations for training CNNs from scratch (or full training) and distinct architectures of pretrained CNNs tested on 8-HD-endoscopic image databases acquired using different modalities. We compare our results with some commonly used features for colonic polyp classification and the good results suggest that features learned by CNNs trained from scratch and the “off-the-shelf” CNNs features can be highly relevant for automated classification of colonic polyps. Moreover, we also show that the combination of classical features and “off-the-shelf” CNNs features can be a good approach to further improve the results.
Cerebrospinal Fluid Leak in Cochlear Implantation: Enlarged Cochlear versus Enlarged Vestibular Aqueduct (Common Cavity Excluded)
Authors: Bianchin Giovanni , Polizzi Valeria , Formigoni Patrizia , Russo Carmela , Tribi Lorenzo
Published: October 2016

Objective. To share our experience of cerebrospinal fluid gusher in cochlear implantation in patients with enlarged cochlear or vestibular aqueduct.Study Design. Case series with comparison and a review of the literature.Methods. A retrospective study was performed.Demographic and radiological results of patients with enlarged cochlear aqueduct or enlarged vestibular aqueduct in 278 consecutive cochlear implant recipients, including children and adults, were evaluated between January 2000 and December 2015.Results. Six patients with enlarged cochlear aqueduct and eight patients with enlarged vestibular aqueduct were identified. Cerebrospinal fluid gusher occurs in five subjects with enlarged cochlear aqueduct and in only one case of enlarged vestibular aqueduct.Conclusion. Based on these findings, enlarged cochlear aqueduct may be the best risk predictor of cerebrospinal fluid gusher at cochleostomy during cochlear implant surgery despite enlarged vestibular aqueduct.
Critical Review on Nanofluids: Preparation, Characterization, and Applications
Authors: Jama Mohamoud , Singh Tejvir , Gamaleldin Seifelislam Mahmoud , Koc Muammer , Samara Ayman , Isaifan Rima J. , Atieh Muataz A.
Published: October 2016

Heat transfer fluids are a crucial parameter that affects the size and costs of heat exchangers. However, the available coolants like water and oils have low thermal conductivities, which put many limitations to the development of heat transfer to achieve high performance cooling. The need for development of new classes of fluids which enhance the heat transfer capabilities attracted the attention of many researchers. In the last few decades, modern nanotechnology developed nanoparticles, which have unique thermal and electrical properties that could help improve heat transfer using nanofluids. A “nanofluid” is a fluid with suspended fine nanoparticles which increases the heat transfer properties compared with the original fluid. Nanofluids are considered a new generation of heat transfer fluids and are considered two-phase fluids of liquid solid mixtures. The efficiency of the fluid could be improved by enhancing its thermal properties, especially the thermal conductivity, and it is expected that the nanofluids will have a greater thermal conductivity than the base fluids. This paper reviews the preparation of metallic and nonmetallic nanofluids along with the stability of the produced nanofluids. Physical and thermal properties as well as a range of applications are also discussed in detail.
Model Study of Information Dissemination in Microblog Community Networks
Authors: Wang Bo , Zhang Jianhua , Guo Haifeng , Zhang Yuwang , Qiao Xiaotuo
Published: October 2016

We build an information dissemination model based on SIR model to study information dissemination in microblog networks. We consider different influence factors of information dissemination such as activity, credibility, and weight of network and construct calculation methods of various parameters, for instance, direct immune rate, indirect immune rate, and information dissemination rate. Meanwhile, by collecting data from API in Weibo and using the result of microblog information dissemination life cycle analysis, we utilize the model to conduct simulation and get the change trend of proportion in Stages S, I, and R. After comparing with the actual situation, this model is proved to be effective in predicting the trend of information dissemination.
On the Motion of Harmonically Excited Spring Pendulum in Elliptic Path Near Resonances
Authors: Amer T. S. , Bek M. A. , Hamada I. S.
Published: October 2016

The response of a nonlinear multidegrees of freedom (M-DOF) for a nature dynamical system represented by a spring pendulum which moves in an elliptic path is investigated. Lagrange’s equations are used in order to derive the governing equations of motion. One of the important perturbation techniques MS (multiple scales) is utilized to achieve the approximate analytical solutions of these equations and to identify the resonances of the system. Besides, the amplitude and the phase variables are renowned to study the steady-state solutions and to recognize their stability conditions. The time history for the attained solutions and the projections of the phase plane are presented to interpret the behavior of the dynamical system. The mentioned model is considered one of the important scientific applications like in instrumentation, addressing the oscillations occurring in sawing buildings and the most of various applications of pendulum dampers.
Transglutaminase Interaction with α6/β4-Integrin Stimulates YAP1-Dependent ΔNp63α Stabilization and Leads to Enhanced Cancer Stem Cell Survival and Tumor Formation
Authors: Fisher Matthew L. , Kerr Candace , Adhikary Gautam , Grun Dan , Xu Wen , Keillor Jeffrey W. , Eckert Richard L.
Published: October 2016

Transglutaminase 2 (TG2) expression is required for epidermal squamous cell carcinoma cancer stem cell survival. However, the molecular signaling mechanisms triggered by TG2 that mediate this survival action are not well understood. Here we show that TG2 is constitutively expressed in ECS cells, where it interacts with α6/β4 integrin to stimulate FAK and Src signaling, leading to PI3K activation of phosphoinositide-dependent kinase 1 (PDK1). PDK1 inhibits Hippo signaling, leading to enhanced nuclear accumulation of YAP1, which interacted with and stabilized ΔNp63α to enhance epidermal squamous cell carcinoma spheroid formation, invasion, and migration. Overall, these findings suggest that constitutive TG2 expression results in stabilization of ΔNp63α, leading to maintenance of cancer stem cell properties and enhanced tumor formation. Cancer Res; 76(24); 7265–76. ©2016 AACR.
Reallocating Time to Sleep, Sedentary Time, or Physical Activity: Associations with Waist Circumference and Body Mass Index in Breast Cancer Survivors
Authors: Boyle Terry , Vallance Jeff K. , Buman Matthew P. , Lynch Brigid M.
Published: October 2016

Background: Moderate-to-vigorous intensity physical activity (MVPA) is inversely associated with waist circumference and body mass index (BMI) among breast cancer survivors. Limited research has focused on behaviors that account for larger portions of the day [sleep, sedentary time, and light-intensity physical activity (LPA)]. We investigated the interdependent associations of self-reported sleep, objectively assessed prolonged and short bouts of sedentary time, total LPA, and total MVPA with waist circumference and BMI.

Methods: A cross-sectional sample of breast cancer survivors (N = 256, mean age = 60 years; mean time since diagnosis = 3 years) wore an Actigraph GT3X+ accelerometer during waking hours for 7 days. Participants completed the Pittsburgh Sleep Quality Index and self-reported their waist circumference, height, and weight. An isotemporal substitution approach was used in linear regression models to explore the associations of reallocating time to sleep, sedentary and active behaviors on waist circumference, and BMI, after adjusting for potential confounders.

Results: Reallocating 30 minutes to MVPA was significantly associated with lower waist circumference when allocated from sleep (−2.50 cm), prolonged sedentary time (−2.51 cm), or LPA (−2.71 cm). Reallocating 30 minutes of prolonged sedentary time to nonprolonged sedentary time was significantly associated with lower waist circumference (−0.94 cm). Similar results were observed for BMI.

Conclusions: Reallocating 30 minutes to MVPA was associated with significantly lower waist circumference and BMI, as was reallocating 30 minutes of prolonged sedentary time to 30 minutes of nonprolonged sedentary time.

Impact: Increasing MVPA levels and decreasing time spent in prolonged, unbroken sedentary bouts may be avenues for improving body composition in this population. Cancer Epidemiol Biomarkers Prev; 26(2); 254–60. ©2016 AACR.
Impact of TP53 Mutations on Outcome in EGFR-Mutated Patients Treated with First-Line Tyrosine Kinase Inhibitors
Authors: Canale Matteo , Petracci Elisabetta , Delmonte Angelo , Chiadini Elisa , Dazzi Claudio , Papi Maximilian , Capelli Laura , Casanova Claudia , De Luigi Nicoletta , Mariotti Marita , Gamboni Alessandro , Chiari Rita , Bennati Chiara , Calistri Daniele , Ludovini Vienna , Crinò Lucio , Amadori Dino , Ulivi Paola
Published: October 2016

Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non–small cell lung cancer (NSCLC).

Experimental Design: 136 EGFR-mutated NSCLC patients receiving first-line TKIs were analyzed. TP53 mutations were evaluated in 123 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: TP53 mutations were observed in 37 (30.1%), 10 (27.0%), 6 (16.2%), 9 (24.3%), and 12 (32.4%) patients in exons 5, 6, 7, and 8, respectively. DCR was 70% in TP53-mutated patients compared with 88% in TP53-wild type (wt) patients [relative risk, RR, of disease progression: 3.17 (95% CI, 1.21–8.48), P = 0.019]. In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation versus 87% in exon 8 wt patients [RR of disease progression 9.6 (2.71–36.63), P < 0.001]. Shorter median PFS and OS were observed in patients with TP53 exon 8 mutations compared with others (4.2 vs. 12.5, P = 0.058, and 16.2 vs. 32.3, P = 0.114, respectively); these differences became significant in the subgroup with EGFR exon 19 deletion (4.2 vs. 16.8, P < 0.001, and 7.6 vs. not reached, P = 0.006, respectively), HR 6.99 (95% CI, 2.34–20.87, P < 0.001) and HR 4.75 (95% CI, 1.38–16.29, P = 0.013), respectively.

Conclusions: TP53 mutations, especially exon 8 mutations, reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions. Clin Cancer Res; 23(9); 2195–202. ©2016 AACR.
The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia
Authors: Vercruysse Thomas , De Bie Jolien , Neggers Jasper E. , Jacquemyn Maarten , Vanstreels Els , Schmid-Burgk Jonathan L. , Hornung Veit , Baloglu Erkan , Landesman Yosef , Senapedis William , Shacham Sharon , Dagklis Antonis , Cools Jan , Daelemans Dirk
Published: October 2016

Purpose: Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports different cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibiting XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained with the Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330) demonstrating activity in phase-II/IIb clinical trials when dosed 1 to 3 times weekly. The second-generation SINE compound KPT-8602 shows improved tolerability and can be dosed daily. Here, we investigate and validate the drug–target interaction of KPT-8602 and explore its activity against acute lymphoblastic leukemia (ALL).

Experimental Design: We examined the effect of KPT-8602 on XPO1 function and XPO1-cargo as well as on a panel of leukemia cell lines. Mutant XPO1 leukemia cells were designed to validate KPT-8602′s drug-target interaction. In vivo, anti-ALL activity was measured in a mouse ALL model and patient-derived ALL xenograft models.

Results: KPT-8602 induced caspase-dependent apoptosis in a panel of leukemic cell lines in vitro. Using CRISPR/Cas9 genome editing, we demonstrated the specificity of KPT-8602 for cysteine 528 in the cargo-binding groove of XPO1 and validated the drug target interaction. In vivo, KPT-8602 showed potent anti-leukemia activity in a mouse ALL model as well as in patient-derived T- and B-ALL xenograft models without affecting normal hematopoiesis.

Conclusions: KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. Clin Cancer Res; 23(10); 2528–41. ©2016 AACR.
5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma
Authors: Kerk Samuel A. , Finkel Kelsey A. , Pearson Alexander T. , Warner Kristy A. , Zhang Zhaocheng , Nör Felipe , Wagner Vivian P. , Vargas Pablo A. , Wicha Max S. , Hurt Elaine M. , Hollingsworth Robert E. , Tice David A. , Nör Jacques E.
Published: October 2016

Purpose: Locoregional recurrence is a frequent treatment outcome for patients with advanced head and neck squamous cell carcinoma (HNSCC). Emerging evidence suggests that tumor recurrence is mediated by a small subpopulation of uniquely tumorigenic cells, that is, cancer stem cells (CSC), that are resistant to conventional chemotherapy, endowed with self-renewal and multipotency.

Experimental Design: Here, we evaluated the efficacy of MEDI0641, a novel antibody–drug conjugate targeted to 5T4 and carrying a DNA-damaging “payload” (pyrrolobenzodiazepine) in preclinical models of HNSCC.

Results: Analysis of a tissue microarray containing 77 HNSCC with follow-up of up to 12 years revealed that patients with 5T4high tumors displayed lower overall survival than those with 5T4low tumors (P = 0.038). 5T4 is more highly expressed in head and neck CSC (ALDHhighCD44high) than in control cells (non-CSC). Treatment with MEDI0641 caused a significant reduction in the CSC fraction in HNSCC cells (UM-SCC-11B, UM-SCC-22B) in vitro. Notably, a single intravenous dose of 1 mg/kg MEDI0641 caused long-lasting tumor regression in three patient-derived xenograft (PDX) models of HNSCC. MEDI0641 ablated CSC in the PDX-SCC-M0 model, reduced it by five-fold in the PDX-SCC-M1, and two-fold in the PDX-SCC-M11 model. Importantly, mice (n = 12) treated with neoadjuvant, single administration of MEDI0641 prior to surgical tumor removal showed no recurrence for more than 200 days, whereas the control group had 7 recurrences (in 12 mice; P = 0.0047).

Conclusions: Collectively, these findings demonstrate that an anti-5T4 antibody–drug conjugate reduces the fraction of CSCs and prevents local recurrence and suggest a novel therapeutic approach for patients with HNSCC. Clin Cancer Res; 23(10); 2516–27. ©2016 AACR.
Heterogeneity of Acquired Resistance to Anti-EGFR Monoclonal Antibodies in Patients with Metastatic Colorectal Cancer
Authors: Pietrantonio Filippo , Vernieri Claudio , Siravegna Giulia , Mennitto Alessia , Berenato Rosa , Perrone Federica , Gloghini Annunziata , Tamborini Elena , Lonardi Sara , Morano Federica , Picciani Benedetta , Busico Adele , Volpi Chiara Costanza , Martinetti Antonia , Battaglin Francesca , Bossi Ilaria , Pellegrinelli Alessio , Milione Massimo , Cremolini Chiara , Di Bartolomeo Maria , Bardelli Alberto , de Braud Filippo
Published: October 2016

Purpose: Even if RAS-BRAF wild-type and HER2/MET–negative metastatic colorectal cancer (mCRC) patients frequently respond to anti-EGFR mAbs, acquired resistance almost invariably occurs. Mechanisms of resistance to EGFR blockade include the emergence of KRAS, NRAS, and EGFR extracellular domain mutations as well as HER2/MET alterations. However, these findings derive from retrospective studies that analyzed one single resistance mechanism at a time; moreover, it is still unclear how molecular heterogeneity affects clonal evolution in patients. In this work, we aimed at extensively characterizing and correlating the molecular characteristics of tissue- and blood-based data in a prospective cohort of patients with mCRC who received anti-EGFR antibodies.

Experimental design: Twenty-two RAS-BRAF wild-type, HER2/MET–negative mCRC patients progressing on anti-EGFR therapy after initial response underwent rebiopsy. Next-generation sequencing and silver in situ hybridization (SISH)/IHC analyses were performed both on archival tumors and postprogression samples. Circulating tumor (ctDNA) molecular profiles were obtained in matched tissue–plasma samples.

Results: RAS mutations and HER2/MET amplification were the most frequently detected resistance mechanisms in both tissue and blood sample analysis. On the other hand, BRAF and EGFR ectodomain mutations were much rarer. Patients with acquired MET amplification showed worse PFS on anti-EGFRs. We detected both intralesion heterogeneity, as suggested by co-occurrence of different resistance mechanisms in the same sample, and interlesion heterogeneity. The combined analysis of tissue and blood (ctDNA) results highlights the complexity of clonal evolution triggered by EGFR blockade.

Conclusions: Our results indicate that it may be extremely challenging to target the complex landscape of molecular heterogeneity associated with emergence of resistance to targeted therapies in patients with mCRC. Clin Cancer Res; 23(10); 2414–22. ©2016 AACR.
Early Prediction of the Outcome Using Tumor Markers and mRECIST in Unresectable Hepatocellular Carcinoma Patients Who Underwent Transarterial Chemoembolization
Authors: Ichikawa Takeshi , Machida Nobuaki , Sasaki Hiroshi , Tenmoku Akira , Kaneko Hiroaki , Negishi Ryoju , Oi Itaru , Fujino Masayuki A.
Published: October 2016

Objective: We examined early predictors of the outcome in hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE). Methods: We analyzed 116 patients with unresectable HCC treated with initial TACE. α-Fetoprotein (AFP) or des-γ-carboxy prothrombin (DCP) response was assessed in patients who had baseline AFP levels ≥200 ng/ml or DCP ≥60 mAU/ml; a positive response was defined as a reduction of >50% compared to baseline 1 month after TACE. Results: A baseline AFP level ≥200 ng/ml was associated with a poor overall survival (OS) (29.4 vs. 6.1 months; p <0.0001). AFP response had no significantly prognostic effects on the OS. Conversely, although the baseline DCP did not influence the OS, DCP responders showed a significantly better OS than nonresponders (67.0 vs. 19.8 months, p = 0.020). The baseline AFP (p = 0.004) and initial tumor response evaluated by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) (p = 0.012) were found to be independent predictors of the OS. The combination of the baseline AFP and initial assessment by mRECIST allowed stratification of the OS. Conclusions: The combination of the baseline AFP level and mRECIST is useful for the early prediction of the OS in HCC patients who underwent TACE.
Arterial Stiffness and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease
Authors: Kim Joong-Seok , Lee Si-Hoon , Oh Yoon-Sang , Park Jeong-Wook , An Jae-Young , Choi Hyun-Seok , Lee Kwang-Soo
Published: October 2016

Background: Pulse wave velocity is a marker of arterial stiffness and a surrogate marker of vascular damage. Autonomic abnormalities associated with blood pressure are relatively commonly observed in patients with Parkinson's disease (PD). Objective: The purpose of this study was to compare arterial stiffness between patients with PD and controls and investigate the associations between cardiovascular autonomic dysfunction and pulse wave velocity in PD. Methods: One hundred twenty-five PD patients without diabetes mellitus were enrolled into this study, along with 22 age-matched controls. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. Pulse wave velocity was used to evaluate arterial stiffness. Results: In PD, greater arterial stiffness was associated with orthostatic hypotension, supine hypertension, nocturnal hypertension, and nondipping. Dopaminergic treatment did not influence cardiovascular autonomic dysfunction or arterial stiffness. Although pulse wave velocity was mildly increased in patients with PD compared to controls, the arterial stiffness in PD patients without autonomic failure was similar to that in normal controls. Stiffer arteries were found only in patients with PD and autonomic failure. Conclusion: These findings suggest that cardiovascular autonomic dysfunction is associated with arterial stiffness in PD. PD itself does not affect arterial stiffness, whereas autonomic blood pressure disturbances influence alterations in arterial stiffness and architectural changes in the arteries of PD patients.