bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Application Mapping onto a Switch-Based Reconfigurable Network-on-Chip Architecture
Authors: Soumya J. , Babu K. Niranjan , Chattopadhyay Santanu
Published: April 2017

This paper presents a reconfigurable architecture for Network-on-Chip (NoC) design based on configuration switches. Reconfiguration is achieved by varying connection pattern between routers, depending on the currently running application. Mapping and reconfiguration strategies have been developed for the proposed architecture. In the mapping phase, cores in the combined application set are mapped to individual routers, minimizing the overall communication cost. In the second phase, for each application, configuration information for the switches (between the routers) are generated to optimize the communication cost further to suit the corresponding application. Exact methods, based on Integer Linear Programming (ILP), have been proposed for both the phases. Since ILP takes a large amount of CPU time, Particle Swarm Optimization (PSO)-based approaches have also been developed. The architecture and mapping strategies have been evaluated against benchmarks, considering communication cost, throughput, latency and network energy before and after reconfiguration. Significant improvements could be achieved via reconfiguration. Compared to the approaches reported in the literature, communication cost, throughput, latency and energy consumption values improve by 23.4%, 4%, 3% and 7%, respectively. These improvements come at a nominal increase in area overhead of 0.07%.
Efficient Complex High-Precision Computations on GPUs without Precision Loss
Authors: Cabodi G. , Garbo A. , Loiacono C. , Quer S. , Francini G.
Published: April 2017

General-purpose computing on graphics processing units is the utilization of a graphics processing unit (GPU) to perform computation in applications traditionally handled by the central processing unit. Many attempts have been made to implement well-known algorithms on embedded and mobile GPUs. Unfortunately, these applications are computationally complex and often require high precision arithmetic, whereas embedded and mobile GPUs are designed specifically for graphics, and thus are very restrictive in terms of input/output, precision, programming style and primitives available.

This paper studies how to implement efficient and accurate high-precision algorithms on embedded GPUs adopting the OpenGL ES language. We discuss the problems arising during the design phase, and we detail our implementation choices, focusing on the SIFT and ALP key-point detectors. We transform standard, i.e., single (or double) precision floating-point computations, to reduced-precision GPU arithmetic without precision loss. We develop a desktop framework to simulate Gaussian Scale Space transforms on all possible target embedded GPU platforms, and with all possible range and precision arithmetic. We illustrate how to re-engineer standard Gaussian Scale Space computations to mobile multi-core parallel GPUs using the OpenGL ES language. We present experiments on a large set of standard images, proving how efficiency and accuracy can be maintained on different target platforms. To sum up, we present a complete framework to minimize future programming effort, i.e., to easily check, on different embedded platforms, the accuracy and performance of complex algorithms requiring high-precision computations.
Small deformations of Helfrich energy minimising surfaces with applications to biomembranes
Authors: Elliott Charles M. , Fritz Hans , Hobbs Graham
Published: April 2017

In this paper, we introduce a mathematical model for small deformations induced by external forces of closed surfaces that are minimisers of Helfrich-type energies. Our model is suitable for the study of deformations of cell membranes induced by the cytoskeleton. We describe the deformation of the surface as a graph over the undeformed surface. A new Lagrangian and the associated Euler–Lagrange equations for the height function of the graph are derived. This is the natural generalisation of the well-known linearisation in the Monge gauge for initially flat surfaces. We discuss energy perturbations of point constraints and point forces acting on the surface. We establish existence and uniqueness results for weak solutions on spheres and on tori. Algorithms for the computation of numerical solutions in the general setting are provided. We present numerical examples which highlight the behaviour of the surface deformations in different settings at the end of the paper.
Multiple Parametric Resonances of Taut Inclined Cables Excited by Deck Vibration
Authors: Qian Chang-Zhao , Chen Chang-Ping
Published: April 2017

A mechanical model is proposed to describe the vibration of a taut inclined cable excited by a deck. The dynamic system is simplified into a one-degree-of-freedom nonlinear system with non-dimensional parameters by using the Galerkin and non-dimensional analysis methods. The periodicity ratio (PR) method is improved and applied to the parameter analysis for the cable system. The frequency ratio between the natural frequency of the cable and the vibration frequency of the deck and the amplitude of deck vibration are the main variable parameters, and nonlinear motion is diagnosed for a large range of parameters. Several forms of motion are distinguished, and the evolution between the forms is studied. Meanwhile, several types of parametric resonance are revealed in different ranges of parameters. The results indicate that the parametric resonance in the case of a 3:2 frequency ratio is significant and should be given more attention.
A Theoretical Treatment of Crowd–Structure Interaction
Authors: Gao Yan-an , Yang Qing-shan
Published: April 2017

A vertical crowd–structure interaction model including the interaction amongst pedestrians is developed to study the structural performances of the supporting structure with social force effect. This model can be used to analyze the vibration problem of footbridge under a large crowd excitation. The social force is firstly introduced to describe the dynamic interaction amongst the bipedal models with damping-spring legs modeling pedestrian movement on a three-dimensional plate structure. The social force determines the walking direction and velocity of pedestrian. Numerical studies show that the structural dynamic performances can be remarkably changed under the crowd action. The natural frequency of structure is decreased and is time-varying with an increase in the crowd density. However, the damping ratio of structure is increased. The proposed model could well describe the crowd–structure dynamic interaction.
ALTERNATIVE METHOD OF UPPER EXTREMITY FUNCTION ASSESSMENT OF STROKE PATIENTS BY ANGULAR KINEMATIC PARAMETERS
Authors: DAUNORAVIČENĖ KRISTINA , LINKEL ARTURAS , ŽIŽIENĖ JURGITA , GRIŠKEVIČIUS JULIUS , JUOCEVIČIUS ALVYDAS , RAUDONYTĖ INGA , PAUK JOLANTA , IDZKOWSKI ADAM , WALENDZIUK WOJCIECH
Published: April 2017

This study focuses on the functional assessment of the upper extremity of stroke patients via analysis of angular kinematics features. Amplitudes and angular velocities of multi-joint movements more precisely describe functional state at different impairment levels. However, the arm movement as a whole could be analyzed by means of joint angle–angle diagrams, which illustrate the 2D trajectory of upper extremity during movement and show the visual ranges of upper extremity in different cycles of motion. The functional range of motion of each upper extremity segment in all patient groups for more accurate assessment of capability was calculated. Moreover, we calculated the area (S) between two curves in joint angle–angle diagrams as a novel index of the complete upper extremity movement range evaluation. Our findings correspond to clinical rates and upper extremity assessment based on joint angle–angle diagrams seems to be a promising method for accurate assessment and/or predicting the outcomes of rehabilitation programs.
Experimental and Statistical Analysis of MgO Nanofluids for Thermal Enhancement in a Novel Flat Plate Heat Pipes
Authors: Pandiaraj P. , Gnanavelbabu A. , Saravanan P.
Published: April 2017

Metallic fluids like CuO, Al2O3, ZnO, SiO2 and TiO2 nanofluids were widely used for the development of working fluids in flat plate heat pipes except magnesium oxide (MgO). So, we initiate our idea to use MgO nanofluids in flat plate heat pipe as a working fluid material. MgO nanopowders were synthesized by wet chemical method. Solid state characterizations of synthesized nanopowders were carried out by Ultraviolet Spectroscopy (UV), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and X-ray Diffraction (XRD) techniques. Synthesized nanopowders were prepared as nanofluids by adding water and as well as water/ethylene glycol as a binary mixture. Thermal conductivity measurements of prepared nanofluids were studied using transient hot-wire apparatus. Response surface methodology based on the Box–Behnken design was implemented to investigate the influence of temperature (30–60[Formula: see text]C), particle fraction (1.5–4.5 vol.%), and solution pH (4–12) of nanofluids as the independent variables. A total of 17 experiments were accomplished for the construction of second-order polynomial equations for target output. All the influential factors, their mutual effects and their quadratic terms were statistically validated by analysis of variance (ANOVA). The optimum stability and thermal conductivity of MgO nanofluids with various temperature, volume fraction and solution pH were predicted and compared with experimental results. The results revealed that increase in particle fraction and pH of MgO nanofluids at certain points would increase thermal conductivity and become stable at nominal temperature.
DME synthesis from methanol over hydrated γ-Al2O3(110) surface in slurry bed using continuum and atomistic models
Authors: Gao Xiao-Yu , Jiao Wei-Hong , Zuo Zhi-Jun , Gao Zhi-Hua , Huang Wei
Published: April 2017

The possible paths of dimethyl ether (DME) synthesis from methanol over hydrated [Formula: see text]-Al2O3(110) in vacuum and liquid paraffin have been investigated by using density functional theory (DFT). Over hydrated [Formula: see text]-Al2O3(110), the three possible paths of methanol dehydration to DME have been investigated by the DFT method in vacuum and liquid paraffin. DME synthesis from methanol is carried out along the same pathway 2CH3OH(g) [Formula: see text] 2* [Formula: see text] 2CH3OH* [Formula: see text] 2CH3O* [Formula: see text] 2H* [Formula: see text] CH3OCH3* [Formula: see text] H2O* in vacuum and liquid paraffin, and the step of highest energy barrier is the reaction of 2CH3O* [Formula: see text] CH3OCH3* [Formula: see text] O*. The energy barrier of the step in liquid paraffin is higher than that in vacuum by 0.33[Formula: see text]eV. The surface acid strength in liquid paraffin decreases over [Formula: see text]-Al2O3(110) surface comparing with vacuum, showing that stronger surface acid strength benefits to DME synthesis. Our result is in consistent with the experiment results.
Torsion gravity for Dirac particles
Authors: Fabbri Luca
Published: April 2017

In this paper, we consider torsion gravity in the case of Dirac field, and by going into the rest frame, we study what happens when a uniform precession as well as a phase is taken into account for the spinor field; we discuss how partially conserved axial-vector currents and torsion-spin attractive potentials justify negative Takabayashi angle and energy smaller than mass: because in this instance the module goes to zero exponentially fast, we obtain stable and localized matter distributions suitable to be regarded as a description of particles.
FLEXIBLE NEW PRODUCT DEVELOPMENT PROCESSES AND APPROPRIABILITY: INTELLECTUAL PROPERTY AND FIRST-MOVER
Authors: LEE YEOLAN , JOHN CARON ST. , FONG ERIC A. , BAO YONGCHUAN
Published: April 2017

Prior research argues that higher levels of innovation require less flexible, or more formalised, new product development (NPD) processes; that is, there is a negative relationship between level of innovation and flexible NPD processes. In this paper, we investigate the moderating role of firms’ appropriability strategies, intellectual property (IP) and first-mover, on the use of flexible NPD processes for different levels of innovation (radical, more innovative, and incremental). Using the Product Development and Management Association Foundation’s 2012 Comparative Performance Assessment Study, this research shows that the greater use of IP and first-mover appropriability strategies is associated with an increased use of flexible NPD processes as the level of innovation moves from incremental to radical. Therefore, the results show that the greater use of these appropriability strategies weakens the negative relationship between level of innovation and flexible NPD processes.
Effects of barium substitution on the sintering behavior, dielectric properties of Ca2Nb2O7ferroelectric ceramics
Authors: Li Chunchun , Xiang Huaicheng , Qin Yuandong , Fang Liang
Published: April 2017

Barium-doped Ca2Nb2O7ceramics were prepared in the form of Ca[Formula: see text]BaxNb2O7(0 [Formula: see text] 0.6) by solid-state reaction. The solubility limit of barium in Ca2Nb2O7was found to be [Formula: see text] based on X-ray diffraction and Raman spectroscopy analysis. When [Formula: see text] 0.4, Ca[Formula: see text]BaxNb2O7solid solutions with a monoclinic perovskites-like layered structure (PLS) were formed, whereas beyond [Formula: see text], a secondary phase CaNb2O6was detected. The dielectric properties obviously depended on the barium substitution. With increasing barium amount, the dielectric constant increased from 33.5 for pure Ca2Nb2O7to 38.6 for [Formula: see text] ([Formula: see text][Formula: see text]MHz). The Curie temperature ([Formula: see text] of the [Formula: see text] sample was 1280[Formula: see text][Formula: see text][Formula: see text]5[Formula: see text]C. The phase transition was confirmed to be the second order.
Hardware Architectures for Embedded Speaker Recognition Applications
Authors: Bouraoui Hasna , Jerad Chadlia , Chattopadhyay Anupam , Hadj-Alouane Nejib Ben
Published: April 2017

Authentication technologies based on biometrics, such as speaker recognition, are attracting more and more interest thanks to the elevated level of security offered by these technologies. Despite offering many advantages, such as remote use and low vulnerability, speaker recognition applications are constrained by the heavy computational effort and the hard real-time constraints. When such applications are run on an embedded platform, the problem becomes more challenging, as additional constraints inherent to this specific domain are added. In the literature, different hardware architectures were used/designed for implementing a process with a focus on a given particular metric. In this article, we give a survey of the state-of-the-art works on implementations of embedded speaker recognition applications. Our aim is to provide an overview of the different approaches dealing with acceleration techniques oriented towards speaker and speech recognition applications and attempt to identify the past, current, and future research trends in the area. Indeed, on the one hand, many flexible solutions were implemented, using either General Purpose Processors or Digital Signal Processors. In general, these types of solutions suffer from low area and energy efficiency. On the other hand, high-performance solutions were implemented on Application Specific Integrated Circuits or Field Programmable Gate Arrays but at the expense of flexibility. Based on the available results, we compare the application requirements vis-à-vis the performance achieved by the systems. This leads to the projection of new research trends that can be undertaken in the future.
Lower Bounds for Constant Query Affine-Invariant LCCs and LTCs
Authors: Bhattacharyya Arnab , Gopi Sivakanth
Published: April 2017

Affine-invariant codes are codes whose coordinates form a vector space over a finite field and which are invariant under affine transformations of the coordinate space. They form a natural, well-studied class of codes; they include popular codes such as Reed-Muller and Reed-Solomon. A particularly appealing feature of affine-invariant codes is that they seem well suited to admit local correctors and testers. In this work, we give lower bounds on the length of locally correctable and locally testable affine-invariant codes with constant query complexity. We show that if a code
C
⊂ Σ

K

n

is an
r
-query affine invariant locally correctable code (LCC), where K is a finite field and Σ is a finite alphabet, then the number of codewords in
C
is at most exp(
O
K,r,|Σ|
(
n

r
−1))

. Also, we show that if
C
⊂ Σ
K
n
is an
r
-query affine invariant locally testable code (LTC), then the number of codewords in
C
is at most exp(
O
K,r,|Σ|
(
n

r
−2))

. The dependence on
n
in these bounds is tight for constant-query LCCs/LTCs, since Guo, Kopparty, and Sudan (ITCS’13) constructed affine-invariant codes via lifting that have the same asymptotic tradeoffs. Note that our result holds for non-linear codes, whereas previously, Ben-Sasson and Sudan (RANDOM’11) assumed linearity to derive similar results. Our analysis uses higher-order Fourier analysis. In particular, we show that the codewords corresponding to an affine-invariant LCC/LTC must be far from each other with respect to Gowers norm of an appropriate order. This then allows us to bound the number of codewords, using known decomposition theorems, which approximate any bounded function in terms of a finite number of low-degree non-classical polynomials, up to a small error in the Gowers norm.
A Single-Tier Virtual Queuing Memory Controller Architecture for Heterogeneous MPSoCs
Authors: Song Yang , Samadi Kambiz , Lin Bill
Published: April 2017

Heterogeneous MPSoCs typically integrate diverse cores, including application CPUs, GPUs, and HD coders. These cores commonly share an off-chip memory to save cost and energy, but their memory accesses often interfere with each other, leading to undesirable consequences like a slowdown of application performance or a failure to sustain real-time performance. The memory controller plays a central role in meeting the QoS needs of real-time cores while maximizing CPU performance. Previous QoS-aware memory controllers are based on a classic two-tier queuing architecture that buffers memory transactions at the first tier, followed by a second tier that buffers translated DRAM commands. In these designs, QoS-aware policies are used to schedule competing transactions at the first stage, but the translated DRAM commands are served in FIFO order at the second stage. Unfortunately, once the scheduled transactions have been forwarded to the command stage, newly arriving transactions that may be more critical cannot be served ahead of those translated commands that are already queued at the second stage. To address this, we propose a scalable memory controller architecture based on single-tier virtual queuing (STVQ) that maintains a single tier of request queues and employs an efficacious scheduler that considers both QoS requirements and DRAM bank states. In comparison with previous QoS-aware memory controllers, the proposed STVQ memory controller reduces CPU slowdown by up to 13.9% while satisfying all frame rate requirements. We propose further optimizations that can significantly increase row-buffer hits by up to 66.2% and reduce memory latency by up to 19.8%.
Obfuscation-Based Protection Framework against Printed Circuit Boards Unauthorized Operation and Reverse Engineering
Authors: Guo Zimu , Di Jia , Tehranipoor Mark M. , Forte Domenic
Published: April 2017

Printed circuit boards (PCBs) are a basic necessity for all modern electronic systems but are becoming increasingly vulnerable to cloning, overproduction, tampering, and unauthorized operation. Most efforts to prevent such attacks have only focused on the chip level, leaving a void for PCBs and higher levels of abstraction. In this article, we propose the first ever obfuscation-based framework for the protection of PCBs. Central to our approach is a permutation block that hides the inter-chip connections between chips on the PCB and is controlled by a key. If the correct key is applied, then the correct connections between chips are made. Otherwise, the connections are incorrectly permuted, and the PCB/system fails to operate. We propose a permutation network added to the PCB based on a Benes network that can easily be implemented in a complex programmable logic device or field-programmable gate arrays. Based on this implementation, we analyze the security of our approach with respect to (i) brute-force attempts to reverse engineer the PCB, (ii) brute-force attempts at guessing the correct key, and (iii) physical and logistic attacks by a range of adversaries. Performance evaluation results on 12 reference designs show that brute force generally requires prohibitive time to break the obfuscation. We also provide detailed requirements for countermeasures that prevent reverse engineering, unauthorized operation, and so on, for different classes of attackers.
Obtaining and Managing Answer Quality for Online Data-Intensive Services
Authors: Kelley Jaimie , Stewart Christopher , Morris Nathaniel , Tiwari Devesh , He Yuxiong , Elnikety Sameh
Published: April 2017

Online data-intensive (OLDI) services use anytime algorithms to compute over large amounts of data and respond quickly. Interactive response times are a priority, so OLDI services parallelize query execution across distributed software components and return best effort answers based on the data so far processed. Omitted data from slow components could lead to better answers, but tracing online how much better the answers could be is difficult. We propose Ubora, a design approach to measure the effect of slow-running components on the quality of answers. Ubora randomly samples online queries and executes them a second time. The first online execution omits data from slow components and provides interactive answers. The second execution uses mature results from intermediate components completed after the online execution finishes. Ubora uses memoization to speed up mature executions by replaying network messages exchanged between components. Our systems-level implementation works for a wide range of services, including Hadoop/Yarn, Apache Lucene, the EasyRec Recommendation Engine, and the OpenEphyra question-answering system. Ubora computes answer quality with more mature executions per second than competing approaches that do not use memoization. With Ubora, we show that answer quality is effective at guiding online admission control. While achieving the same answer quality on high-priority queries, our adaptive controller had 55% higher peak throughput on low-priority queries than a competing controller guided by the rate of timeouts.
V-JAUNE
Authors: Hussein Fairouz , Piccardi Massimo
Published: April 2017

Video summarization and action recognition are two important areas of multimedia video analysis. While these two areas have been tackled separately to date, in this article, we present a latent structural SVM framework to recognize the action and derive the summary of a video in a joint, simultaneous fashion. Efficient inference is provided by a submodular score function that accounts for the action and summary jointly. In this article, we also define a novel measure to evaluate the quality of a predicted video summary against the annotations of multiple annotators. Quantitative and qualitative results over two challenging action datasets—the ACE and MSR DailyActivity3D datasets—show that the proposed joint approach leads to higher action recognition accuracy and equivalent or better summary quality than comparable approaches that perform these tasks separately.
From stereoscopes to holograms
Authors: Sokohl Joe
Published: April 2017

The
Interactions
website (interactions.acm.org) hosts a stable of bloggers who share insights and observations on HCI, often challenging current practices. Each issue we'll publish selected posts from some of the leading voices in the field.
From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohn’s disease
Authors: Balasubramanian Iyshwarya , Gao Nan
Published: April 2017

NOD2 was the first susceptibility gene identified for Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-κB pathway to induce antimicrobial activities, however, defective or loss of NOD2 functions incur a similarly activated inflammatory response. Additional studies have identified the involvement of NOD2 in protection against non-microbiota-related intestinal damages as well as extraintestinal infections. We survey recent molecular and genetic studies of NOD2-mediated bacterial sensing and immunological modulation, and integrate evidence to suggest a highly reciprocal but still poorly understood cross talk between enteric microbiota and host cells.
Surfactant replacement therapy reduces acute lung injury and collapse induration-related lung remodeling in the bleomycin model
Authors: Steffen Lilian , Ruppert Clemens , Hoymann Heinz-Gerd , Funke Manuela , Ebener Simone , Kloth Christina , Mühlfeld Christian , Ochs Matthias , Knudsen Lars , Lopez-Rodriguez Elena
Published: April 2017

Bleomycin-induced lung injury leads to surfactant dysfunction and permanent loss of alveoli due to a remodeling process called collapse induration. Collapse induration also occurs in acute interstitial lung disease and idiopathic pulmonary fibrosis in humans. We hypothesized that surfactant dysfunction aggravates lung injury and early remodeling resulting in collapse induration within 7 days after lung injury. Rats received bleomycin to induce lung injury and either repetitive surfactant replacement therapy (SRT: 100 mg Curosurf/kg BW = surf group) or saline (0.9% NaCl = saline group). After 3 (D3) or 7 (D7) days, invasive pulmonary function tests were performed to determine tissue elastance (H) and static compliance (Cst). Bronchoalveolar lavage (BAL) was taken for surfactant function, inflammatory markers, and protein measurements. Lungs were fixed by vascular perfusion for design-based stereology and electron microscopic analyses. SRT significantly improved minimum surface tension of alveolar surfactant as well as H and Cst at D3 and D7. At D3 decreased inflammatory markers including neutrophilic granulocytes, IL-1β, and IL-6 correlated with reduced BAL-protein levels after SRT. Numbers of open alveoli were significantly increased at D3 and D7 in SRT groups whereas at D7 there was also a significant reduction in septal wall thickness and parenchymal tissue volume. Septal wall thickness and numbers of open alveoli highly correlated with improved lung mechanics after SRT. In conclusion, reduction in surface tension was effective to stabilize alveoli linked with an attenuation of parameters of acute lung injury at D3 and collapse induration at D7. Hence, SRT modifies disease progression to collapse induration.
Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells
Authors: Pan Shi , Sharma Pawan , Shah Sushrut D. , Deshpande Deepak A.
Published: April 2017

Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases.
Exercise-induced modification of the skeletal muscle transcriptome in Arabian horses
Authors: Ropka-Molik Katarzyna , Stefaniuk-Szmukier Monika , Z˙ukowski Kacper , Piórkowska Katarzyna , Bugno-Poniewierska Monika
Published: April 2017

It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase), and T2 (horses at the end of racing season), 23 samples in total. The numerous groups of exercise-regulated differentially expressed genes (DEGs) were related to muscle cell structure and signaling and included insulin-like growth factor 1 receptor ( IGF1R), insulin receptor ( INSR), transforming growth factor beta receptors 1 and 2 ( TGFBR1, TGFBR2), vascular endothelial growth factor B ( VEGFB); epidermal growth factor ( EGF), hepatocyte growth factor ( HGF), and vascular endothelial growth factor D ( FIGF). In Arabian horses, exercise modified the expression of genes belonging to the PPAR signaling pathway (e.g., PPARA, PPARD, and PLIN2), calcium signaling pathway, and pathways associated with metabolic processes (e.g., oxidative phosphorylation, fatty acid metabolism, glycolysis/gluconeogenesis, and citrate cycle). According to detected gene expression modifications, our results suggested that in Arabian horses, exercise switches energy generation toward fatty acid utilization and enhances glycogen transport and calcium signaling. The use of the RNA-Seq approach in analyzing the skeletal muscle transcriptome allowed for the proposal of a panel of new candidate genes potentially related to body homeostasis maintenance and racing performance in Arabian horses.
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors
Authors: Quigley David , Alumkal Joshi J. , Wyatt Alexander W. , Kothari Vishal , Foye Adam , Lloyd Paul , Aggarwal Rahul , Kim Won , Lu Eric , Schwartzman Jacob , Beja Kevin , Annala Matti , Das Rajdeep , Diolaiti Morgan , Pritchard Colin , Thomas George , Tomlins Scott , Knudsen Karen , Lord Christopher J. , Ryan Charles , Youngren Jack , Beer Tomasz M. , Ashworth Alan , Small Eric J. , Feng Felix Y.
Published: April 2017

Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2. HRR defects confer synthetic lethality to PARP inhibitors (PARPi) such as olaparib and talazoparib. In ovarian or breast cancers, olaparib resistance has been associated with HRR restoration, including by BRCA2 mutation reversion. Whether similar mechanisms operate in prostate cancer, and could be detected in liquid biopsies, is unclear. Here, we identify BRCA2 reversion mutations associated with olaparib and talazoparib resistance in patients with prostate cancer. Analysis of circulating cell-free DNA (cfDNA) reveals reversion mutation heterogeneity not discernable from a single solid-tumor biopsy and potentially allows monitoring for the emergence of PARPi resistance.

Significance: The mechanisms of clinical resistance to PARPi in DNA repair–deficient prostate cancer have not been described. Here, we show BRCA2 reversion mutations in patients with prostate cancer with metastatic disease who developed resistance to talazoparib and olaparib. Furthermore, we show that PARPi resistance is highly multiclonal and that cfDNA allows monitoring for PARPi resistance. Cancer Discov; 7(9); 999–1005. ©2017 AACR.

See related commentary by Domchek, p. 937.

See related article by Kondrashova et al., p. 984.

See related article by Goodall et al., p. 1006.

This article is highlighted in the In This Issue feature, p. 920
Inhaled Glucocorticoids and Pneumonia in Preterm Infants: Post Hoc Results from the NEuroSIS Trial
Authors: Koch Alexander , Kreutzer Karen , von Oldershausen Gabriele , Poets Christian F. , Bassler Dirk ,   on behalf of the NEuroSIS Trial Group
Published: April 2017

Background: Inhaled glucocorticoids may increase the risk of pneumonia in adults. Thus, respiratory infections may be a potential explanation for the non-significantly increased mortality seen in the glucocorticoid group in the largest randomized trial on inhaled glucocorticoids for preventing bronchopulmonary dysplasia in preterm infants published to date (NEuroSIS). Objective: To evaluate the effect of inhaled budesonide on the risk of death due to respiratory infections in the NEuroSIS trial. Methods: We performed post hoc analyses of prospectively collected data from 856 preterm infants on presumed but not culture-proven sepsis and antimicrobial drug use. Additionally, pulmonary complications reported on adverse event forms, death certificates and autopsy reports were compared between study groups. Results: Treatment groups did not differ in the number of episodes with suspected sepsis (184/437 [42.1%] in the budesonide vs. 171/419 [40.8%] in the placebo group). Neither the number of patients receiving antimicrobial drugs nor the length of antimicrobial treatment differed between groups. Our analyses for pulmonary adverse events as well as for pulmonary complications reported on death certificates and autopsy reports did not suggest a negative impact of inhaled budesonide on these outcomes. Conclusion: The current analysis does not support the assumption that respiratory tract infections explain the increased mortality seen in the glucocorticoid group in the NEuroSIS trial.
An Uncommon Cause of Small Bowel Bleeding from Appendiceal Carcinoma
Authors: Boonpipattanapong Teeranut , Attasaranya Siriboon , Kayasut Kanita , Sangkhathat Surasak , Ovartlarnporn Bancha
Published: April 2017

Massive hematochezia caused by a small bowel lesion is a rare entity. Currently, video capsule endoscopy and balloon-assisted enteroscopy are effective in identifying the source of small intestine bleeding. Herein, we report a case of small bowel bleeding caused by a nonmucinous appendiceal adenocarcinoma with ileal invasion which was detected by video capsule endoscopy and single-balloon endoscopy. Despite the advanced disease stage with hepatic and peritoneal metastases, as of September 2016 the patient has had 8 years’ disease-free survival after surgical resection and chemotherapy.
Prevalence of Major Comorbidities in Chronic Obstructive Pulmonary Disease Caused by Biomass Smoke or Tobacco
Authors: Golpe Rafael , Martín-Robles Irene , Sanjuán-López Pilar , Cano-Jiménez Esteban , Castro-Añon Olalla , Mengual-Macenlle Noemí , Pérez-de-Llano Luis
Published: April 2017

Background: Comorbidities are very common in chronic obstructive pulmonary disease (COPD), contributing to the overall severity of the disease. The relative prevalence of comorbidities in COPD caused by biomass smoke (B-COPD), compared with COPD related to tobacco (T-COPD), is not well known. Objectives: To establish if both types of COPD are associated with a different risk for several major comorbidities. Method: The prevalence of comorbidities was compared in 863 subjects with B-COPD (n = 179, 20.7%) or T-COPD (n = 684, 79.2%). Multivariate analysis was carried out to explore the independent relationship between comorbidities and type of exposure. Results: Three comorbidities were more frequent in T-COPD than in B-COPD: ischemic heart disease (11.5 vs. 5.0%, respectively, p = 0.01), peripheral vascular disease (9.2 vs. 2.7%, p = 0.006), and peptic ulcer disease (4.8% vs. 0, p = 0.005). After correcting for potential confounding variables, the risk of ischemic heart disease was lower in B-COPD than in T-COPD (OR: 0.33, 95% CI: 0.16-0.69, p = 0.003). Conclusions: The prevalence of ischemic heart disease is significantly lower in B-COPD than in T-COPD, suggesting a different systemic effect of both types of smoke in COPD patients.
Congenital Curved Nail of the Fourth Toe Associated with Oral Disorders
Authors: Di Chiacchio Nilton , Noriega Leandro , Di Chiacchio Nilton Gioia , Ocampo-Garza Jorge , Padoveze Emerson Henrique
Published: April 2017

Congenital curved nail of the fourth toe represents an unusual deformity in which the nail of the fourth toe curves in a plantar direction. It is unknown why only this toe is affected; however, the initial descriptions suggest that this is a mesodermal defect. We describe a case of congenital curved nail of the fourth toe associated with bifid uvula. There are only 2 reports mentioning the association of this nail abnormality with cleft palate and/or lip. In our patient, there was an association with bifid uvula that is considered a minor form of palatine fissure. There seems to be an association of congenital curved nail of the fourth toe with cleft palate to different degrees; however, the pathogenesis of the deformity remains unknown.
Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways
Authors: Jia Xiao-Jian , Li Xi , Wang Feng , Liu Han-Qing , Zhang Da-Jun
Published: April 2017

Background/Aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.
Molecular Imaging of Atherothrombotic Diseases
Authors: Wang Xiaowei , Peter Karlheinz
Published: April 2017

Molecular imaging, with major advances in the development of both innovative targeted contrast agents/particles and radiotracers, as well as various imaging technologies, is a fascinating, rapidly growing field with many preclinical and clinical applications, particularly for personalized medicine. Thrombosis in either the venous or the arterial system, the latter typically caused by rupture of unstable atherosclerotic plaques, is a major determinant of mortality and morbidity in patients. However, imaging of the various thrombotic complications and the identification of plaques that are prone to rupture are at best indirect, mostly unreliable, or not available at all. The development of molecular imaging toward diagnosis and prevention of thrombotic disease holds promise for major advance in this clinically important field. Here, we review the medical need and clinical importance of direct molecular imaging of thrombi and unstable atherosclerotic plaques that are prone to rupture, thereby causing thrombotic complications such as myocardial infarction and ischemic stroke. We systematically compare the advantages/disadvantages of the various molecular imaging modalities, including X-ray computed tomography, magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, fluorescence imaging, and ultrasound. We further systematically discuss molecular targets specific for thrombi and those characterizing unstable, potentially thrombogenic atherosclerotic plaques. Finally, we provide examples for first theranostic approaches in thrombosis, combining diagnosis, targeted therapy, and monitoring of therapeutic success or failure. Overall, molecular imaging is a rapidly advancing field that holds promise of major benefits to many patients with atherothrombotic diseases.
Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading
Authors: Tian Hongyu , Ketova Tatiana , Hardy Duriel , Xu Xiaojiang , Gao Xia , Zijlstra Andries , Blobe Gerard C.
Published: April 2017

Objective—

Endoglin, a transforming growth factor-β superfamily coreceptor, is predominantly expressed in endothelial cells and has essential roles in vascular development. However, whether endoglin is also expressed in vascular smooth muscle cells (VSMCs), especially in vivo, remains controversial. Furthermore, the roles of endoglin in VSMC biology remain largely unknown. Our objective was to examine the expression and determine the function of endoglin in VSMCs during angiogenesis.

Approach and Results—

Here, we determine that endoglin is robustly expressed in VSMCs. Using CRISPR/CAS9 knockout and short hairpin RNA knockdown in the VSMC/endothelial coculture model system, we determine that endoglin in VSMCs, but not in endothelial cells, promotes VSMCs recruitment by the endothelial cells both in vitro and in vivo. Using an unbiased bioinformatics analysis of RNA sequencing data and further study, we determine that, mechanistically, endoglin mediates VSMC recruitment by promoting VSMC migration and spreading on endothelial cells via increasing integrin/FAK pathway signaling, whereas endoglin has minimal effects on VSMC adhesion to endothelial cells. In addition, we further determine that loss of endoglin in VSMCs inhibits VSMC recruitment in vivo.

Conclusions—

These studies demonstrate that endoglin has an important role in VSMC recruitment and blood vessel maturation during angiogenesis and also provide novel insights into how discordant endoglin function in endothelial and VSMCs may regulate vascular maturation and angiogenesis.
Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis
Authors: Safouris Apostolos , Krogias Christos , Sharma Vijay K. , Katsanos Aristeidis H. , Faissner Simon , Roussopoulou Andromachi , Zompola Christina , Kneiphof Janina , Kargiotis Odysseas , Deftereos Spyridon , Giannopoulos Georgios , Triantafyllou Nikos , Voumvourakis Konstantinos , Vadikolias Konstantinos , Tsivgoulis Georgios
Published: April 2017

Objective—

Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited.

Approach and Results—

We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (
P
=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (
P
=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09–0.92;
P
=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07–10.0;
P
=0.037).

Conclusions—

We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.
Circadian Control of Inflammatory Processes in Atherosclerosis and Its Complications
Authors: Steffens Sabine , Winter Carla , Schloss Maximilian J. , Hidalgo Andres , Weber Christian , Soehnlein Oliver
Published: April 2017

Physiological cardiovascular functions show daily diurnal variations, which are synchronized by intrinsic molecular clocks and environment-driven cues. The clinical manifestation of cardiovascular disease also exhibits diurnal variation, with an increased incidence in the early morning. This coincides with circadian oscillations of circulating parameters, such as hormones and leukocyte counts. We are just at the beginning of understanding how circadian rhythms of immune functions are related to cardiovascular disease progression and outcome after an acute ischemic event. Here, we briefly summarize clinical data on oscillations of circulating inflammatory parameters, as well as experimental evidences for the role of circadian clocks in atherosclerosis, postmyocardial infarction inflammatory responses, and cardiac healing.