bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Commitment Value and Commitment Optimal Strategies in Bimatrix Games
Authors: Leonardos Stefanos , Melolidakis Costis
Published: January 2018

Given a bimatrix game, the associated leadership or commitment games are defined as the games at which one player, the leader, commits to a (possibly mixed) strategy and the other player, the follower, chooses his strategy after being informed of the irrevocable commitment of the leader (but not of its realization in case it is mixed). Based on a result by Von Stengel and Zamir [2010], the notions of commitment value and commitment optimal strategies for each player are discussed as a possible solution concept. It is shown that in nondegenerate bimatrix games (a) pure commitment optimal strategies together with the follower’s best response constitute Nash equilibria, and (b) strategies that participate in a completely mixed Nash equilibrium are strictly worse than commitment optimal strategies, provided they are not matrix game optimal. For various classes of bimatrix games that generalize zero-sum games, the relationship between the maximin value of the leader’s payoff matrix, the Nash equilibrium payoff and the commitment optimal value are discussed. For the Traveler’s Dilemma, the commitment optimal strategy and commitment value for the leader are evaluated and seem more acceptable as a solution than the unique Nash equilibrium. Finally, the relationship between commitment optimal strategies and Nash equilibria in [Formula: see text] bimatrix games is thoroughly examined and in addition, necessary and sufficient conditions for the follower to be worse off at the equilibrium of the leadership game than at any Nash equilibrium of the simultaneous move game are provided.
Nuclear norm based two-dimensional sparse principal component analysis
Authors: Chen Yudong , Lai Zhihui , Wen Jiajun , Gao Can
Published: January 2018

Two-Dimensional Principal Component Analysis (2D-PCA) is one of the most simple and effective feature extraction methods in the field of pattern recognition. However, the traditional 2D-PCA lacks robustness and the function of sparse feature extraction. In this paper, we propose a new feature extraction approach based on the traditional 2D-PCA, which is called Nuclear Norm Based Two-Dimensional Sparse Principal Component Analysis (N-2D-SPCA). To improve the robustness of 2D-PCA, we utilize nuclear norm to measure the reconstruction error of loss function. At the same time, we obtain sparse feature extraction by adding [Formula: see text]-norm and [Formula: see text]-norm regularization terms to the model. By designing an alternatively iterative algorithm, we can solve the optimization problem and learn a projection matrix for use with feature extraction. Besides, we present a bilateral projections model (BN-2D-SPCA) to further compress the dimensions of the feature matrix. We verify the effectiveness of our method on four benchmark face databases including AR, ORL, FERET and Yale databases. Experimental results show that the proposed method is more robust than some state-of-the-art methods and the traditional 2D-PCA.
Power minimization for dynamically reconfigurable FPGA partitioning
Authors: Tai Tzu-Chiang , Lai Yen-Tai
Published: January 2018

Dynamically reconfigurable FPGA (DRFPGA) implements a given circuit system by partitioning it into stages and then executing each stage sequentially. Traditionally, the number of communication buffers is minimized. In this article, we study the partitioning problem targeting at power minimization for the DRFPGAs that have lookup table (LUT) based logic blocks. We analyze the power consumption caused by the communication buffers in the temporal partitioning. Based on the analysis, we use a flow network to represent a given circuit so that the power consumption of buffers is correctly evaluated and the temporal constraints are satisfied in circuit partitioning. The well known flow-based FBB algorithm is then applied to the network to find the area-balanced partitioning of minimum power consumption. Experimental results show that our method outperforms the conventional partitioning algorithms in terms of power consumption. The problem is then extended to include constraints on the number of communication buffers. We provide a net modeling for this extended problem and present an extension of the FBB algorithm to obtain a power-optimal solution. Experimental results demonstrate the effectiveness of the proposed algorithm in reducing power consumption as compared to the previous partitioning algorithms without exceeding the buffer number limit.
Adaptive loop caching using lightweight runtime control flow analysis
Authors: Rawlins Marisha , Gordon-Ross Ann
Published: January 2018

Loop caches provide an effective method for decreasing memory hierarchy energy consumption by storing frequently executed code (critical regions) in a more energy efficient structure than the level one cache. However, due to code structure restrictions or costly design time pre-analysis efforts, previous loop cache designs are not suitable for all applications and system scenarios. We present an adaptive loop cache that is amenable to a wider range of system scenarios, which can provide an additional 20% average instruction cache energy savings (with individual benchmark energy savings as high as 69%) compared to the next best loop cache, the preloaded loop cache.
Implementation strategy for downgraded flash-memory storage devices
Authors: Hsieh Jen-Wei , Chang Yuan-Hao , Chu Yuan-Sheng
Published: January 2018

In recent years, low-cost flash-memory devices have contributed greatly to the rapid growth of the flash memory market. Given that the most of the cost of such devices is the cost of the flash-memory chips, many vendors are managing the cost of such devices by using flash-memory chips of low quality, and they will continue to do so in the near future. Recognizing strong market demand, this work presents a set-based mapping strategy with an effective implementation and low hardware resource requirements for making downgraded flash-memory chips useable in products. A configurable management design for managing chips of various qualities with improved lifetime is presented. The effectiveness of the proposed strategy is evaluated by performing a series of experiments and analyzed with reference to popular implementations in industry.
Hot-LSNs distributing wear-leveling algorithm for flash memory
Authors: Kwon Se Jin , Chung Tae-Sun
Published: January 2018

Flash memory offers attractive features, such as non-volatile, shock resistance, fast access and low power consumption for data storage. However, it has one main drawback of requiring an erase before updating the contents. Furthermore, the flash memory can only be erased for a limited number of times. These characteristics are controlled by a software layer called the flash translation layer (FTL). FTL efficiently manages read, write, and erase operations to enhance the overall performance, and considers wear-leveling to prolong the durability of flash memory. In this article, we identify the logical sector numbers corresponding to random data, termed as hot-LSNs, and distribute them to all available blocks without degrading the performance of the flash memory. From our evaluation, we found that the extra erase operations for distributing the hot-LSNs are very low compared to the overall performance. Even though Hot-LSNs Distributing Wear-Leveling Algorithm (Hot-DL) incorporates wear-leveling in the performance enhancing algorithm, Hot-DL only requires approximately 0.015% of extra erase operations compared to previous well-optimized performance enhancing algorithms, shared buffer scheme.
Emotion Recognition Using Multiple Kernel Learning toward E-learning Applications
Authors: Akputu Oryina Kingsley , Seng Kah Phooi , Lee Yunli , Ang Li-Minn
Published: January 2018

Adaptive Educational Hypermedia (AEH) e-learning models aim to personalize educational content and learning resources based on the needs of an individual learner. The Adaptive Hypermedia Architecture (AHA) is a specific implementation of the AEH model that exploits the cognitive characteristics of learner feedback to adapt resources accordingly. However, beside cognitive feedback, the learning realm generally includes both the affective and emotional feedback of the learner, which is often neglected in the design of e-learning models. This article aims to explore the potential of utilizing affect or emotion recognition research in AEH models. The framework is referred to as Multiple Kernel Learning Decision Tree Weighted Kernel Alignment (MKLDT-WFA). The MKLDT-WFA has two merits over classical MKL. First, the WFA component only preserves the relevant kernel weights to reduce redundancy and improve the discrimination for emotion classes. Second, training via the decision tree reduces the misclassification issues associated with the SimpleMKL. The proposed work has been evaluated on different emotion datasets and the results confirm the good performances. Finally, the conceptual Emotion-based E-learning Model (EEM) with the proposed emotion recognition framework is proposed for future work.
A Survey on Online Judge Systems and Their Applications
Authors: Wasik Szymon , Antczak Maciej , Badura Jan , Laskowski Artur , Sternal Tomasz
Published: January 2018

Online judges are systems designed for the reliable evaluation of algorithm source code submitted by users, which is next compiled and tested in a homogeneous environment. Online judges are becoming popular in various applications. Thus, we would like to review the state of the art for these systems. We classify them according to their principal objectives into systems supporting organization of competitive programming contests, enhancing education and recruitment processes, facilitating the solving of data mining challenges, online compilers and development platforms integrated as components of other custom systems. Moreover, we introduce a formal definition of an online judge system and summarize the common evaluation methodology supported by such systems. Finally, we briefly discuss an Optil.io platform as an example of an online judge system, which has been proposed for the solving of complex optimization problems. We also analyze the competition results conducted using this platform. The competition proved that online judge systems, strengthened by crowdsourcing concepts, can be successfully applied to accurately and efficiently solve complex industrial- and science-driven challenges.
Multi-Robot Assembly Strategies and Metrics
Authors: Marvel Jeremy A. , Bostelman Roger , Falco Joe
Published: January 2018

We present a survey of multi-robot assembly applications and methods and describe trends and general insights into the multi-robot assembly problem for industrial applications. We focus on fixtureless assembly strategies featuring two or more robotic systems. Such robotic systems include industrial robot arms, dexterous robotic hands, and autonomous mobile platforms, such as automated guided vehicles. In this survey, we identify the types of assemblies that are enabled by utilizing multiple robots, the algorithms that synchronize the motions of the robots to complete the assembly operations, and the metrics used to assess the quality and performance of the assemblies.
Joint Estimation of Age and Expression by Combining Scattering and Convolutional Networks
Authors: Yang Huei-Fang , Lin Bo-Yao , Chang Kuang-Yu , Chen Chu-Song
Published: January 2018

This article tackles the problem of joint estimation of human age and facial expression. This is an important yet challenging problem because expressions can alter face appearances in a similar manner to human aging. Different from previous approaches that deal with the two tasks independently, our approach trains a convolutional neural network (CNN) model that unifies ordinal regression and multi-class classification in a single framework. We demonstrate experimentally that our method performs more favorably against state-of-the-art approaches.
Kernels for (Connected) Dominating Set on Graphs with Excluded Topological Minors
Authors: Fomin Fedor V. , Lokshtanov Daniel , Saurabh Saket , Thilikos Dimitrios M.
Published: January 2018

We give the first linear kernels for the D
ominating
S
et
and C
onnected
D
ominating
S
et
problems on graphs excluding a fixed graph
H
as a topological minor. In other words, we prove the existence of polynomial time algorithms that, for a given
H
-topological-minor-free  graph
G
and a positive integer
k
, output an
H
-topological-minor-free  graph
G
′
on
O
(
k
) vertices such that
G
has a (connected) dominating set of size
k
if and only if
G
′
has one.

Our results extend the known classes of graphs on which the D
ominating
S
et
and C
onnected
D
ominating
S
et
problems admit linear kernels. Prior to our work, it was known that these problems admit linear kernels on graphs excluding a fixed apex graph
H
as a minor. Moreover, for D
ominating
S
et
, a kernel of size
k

c
(
H
)

, where
c
(
H
) is a constant depending on the size of
H
, follows from a more general result on the kernelization of D
ominating
S
et
on graphs of bounded degeneracy. Alon and Gutner explicitly asked whether one can obtain a linear kernel for D
ominating
S
et
on
H
-minor-free  graphs. We answer this question in the affirmative and in fact prove a more general result. For C
onnected
D
ominating
S
et
no polynomial kernel even on
H
-minor-free  graphs was known prior to our work. On the negative side, it is known that C
onnected
D
ominating
S
et
on 2-degenerated graphs does not admit a polynomial kernel unless coNP ⊆ NP/poly.

Our kernelization algorithm is based on a non-trivial combination of the following ingredients

• The structural theorem of Grohe and Marx [STOC 2012] for graphs excluding a fixed graph
H
as a topological minor;

• A novel notion of protrusions, different than the one defined in [FOCS 2009];

• Our results are based on a generic reduction rule that produces an equivalent instance (in case the input graph is
H
-minor-free) of the problem, with treewidth
O
(√
k
). The application of this rule in a divide-and-conquer fashion, together with the new notion of protrusions, gives us the linear kernels.

A protrusion in a graph [FOCS 2009] is a subgraph of constant treewidth which is separated from the rest of the graph by at most a constant number of vertices. In our variant of protrusions, instead of stipulating that the subgraph be of constant
treewidth
, we ask that it contains a
constant number of vertices from a solution
. We believe that this new take on protrusions would be useful for other graph problems and in different algorithmic settings.
Adaptive Fractional-Pixel Motion Estimation Skipped Algorithm for Efficient HEVC Motion Estimation
Authors: Pan Zhaoqing , Lei Jianjun , Zhang Yajuan , Wang Fu Lee
Published: January 2018

High-Efficiency Video Coding (HEVC) efficiently addresses the storage and transmit problems of high-definition videos, especially for 4K videos. The variable-size Prediction Units (PUs)--based Motion Estimation (ME) contributes a significant compression rate to the HEVC encoder and also generates a huge computation load. Meanwhile, high-level encoding complexity prevents widespread adoption of the HEVC encoder in multimedia systems. In this article, an adaptive fractional-pixel ME skipped scheme is proposed for low-complexity HEVC ME. First, based on the property of the variable-size PUs--based ME process and the video content partition relationship among variable-size PUs, all inter-PU modes during a coding unit encoding process are classified into root-type PU mode and children-type PU modes. Then, according to the ME result of the root-type PU mode, the fractional-pixel ME of its children-type PU modes is adaptively skipped. Simulation results show that, compared to the original ME in HEVC reference software, the proposed algorithm reduces ME encoding time by an average of 63.22% while encoding efficiency performance is maintained.
Automatic Reformulation of ODEs to Systems of First-Order Equations
Authors: Birkisson Ásgeir
Published: January 2018

Most numerical ODE solvers require problems to be written as systems of first-order differential equations. This normally requires the user to rewrite higher-order differential equations as coupled first-order systems. Here, we introduce the treeVar class, written in object-oriented Matlab, which is capable of algorithmically reformulating higher-order ODEs to equivalent systems of first-order equations. This allows users to specify problems using a more natural syntax and saves them from having to manually derive the first-order reformulation. The technique works by using operator overloading to build up syntax trees of expressions as mathematical programs are evaluated. It then applies a set of rules to the resulting trees to obtain the first-order reformulation, which is returned as another program. This technique has connections with algorithmic/automatic differentiation. We present how treeVar has been incorporated in Chebfun, greatly improving the ODE capabilities of the system.
Understanding and Combating Memory Bloat in Managed Data-Intensive Systems
Authors: Nguyen Khanh , Wang Kai , Bu Yingyi , Fang Lu , Xu Guoqing
Published: January 2018

The past decade has witnessed increasing demands on data-driven business intelligence that led to the proliferation of data-intensive applications. A managed object-oriented programming language such as Java is often the developer’s choice for implementing such applications, due to its quick development cycle and rich suite of libraries and frameworks. While the use of such languages makes programming easier, their automated memory management comes at a cost. When the managed runtime meets large volumes of input data, memory bloat is significantly magnified and becomes a scalability-prohibiting bottleneck.

This article first studies, analytically and empirically, the impact of bloat on the performance and scalability of large-scale, real-world data-intensive systems. To combat bloat, we design a novel compiler framework, called F
acade
, that can generate highly efficient data manipulation code by automatically transforming the
data path
of an existing data-intensive application. The key treatment is that in the generated code, the number of runtime heap objects created for data classes in each thread is (almost)
statically bounded
, leading to significantly reduced memory management cost and improved scalability. We have implemented F
acade
and used it to transform seven common applications on three real-world, already well-optimized data processing frameworks: GraphChi, Hyracks, and GPS. Our experimental results are very positive: the generated programs have (1) achieved a 3% to 48% execution time reduction and an up to 88× GC time reduction, (2) consumed up to 50% less memory, and (3) scaled to much larger datasets.
CoCoA-5.2.2 and CoCoALib
Authors: Abbott John , Bigatti Anna M.
Published: January 2018

CoCoA-5 is an interactive Computer Algebra System for Computations in Commutative Algebra, particularly Gröbner bases. It offers a dedicated, mathematician-friendly programming language, with many built-in functions. Its mathematical core is a user-friendly C++ library, called CoCoALib; being a software library facilitates integration with other software. The software is free and open source (C++, GPL3).

CoCoALib has been designed so that other "external" software libraries can be easily integrated with it, and also made accessible via CoCoA-5.

We give an overview of CoCoA-5 and CoCoALib, highlighting the latest developments.
Cigarette smoke dampens antiviral signaling in small airway epithelial cells by disrupting TLR3 cleavage
Authors: Duffney Parker F. , McCarthy Claire E. , Nogales Aitor , Thatcher Thomas H. , Martinez-Sobrido Luis , Phipps Richard P. , Sime Patricia J.
Published: January 2018

Cigarette smokers and people exposed to second-hand smoke are at an increased risk for pulmonary viral infections, and yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection, we used an air-liquid interface culture system and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke, followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV). We found that prior smoke exposure strongly inhibited production of proinflammatory (interleukin-6 and interleukin-8) and antiviral [interferon-γ-induced protein 10 (IP-10) and interferons] mediators in SAECs in response to poly I:C and IAV infection. Impaired antiviral responses corresponded to increased infection with IAV. This was associated with a decrease in phosphorylation of the key antiviral transcription factor interferon response factor 3 (IRF3). Here, we found that cigarette smoke exposure inhibited activation of Toll-like receptor 3 (TLR3) by impairing TLR3 cleavage, which was required for downstream phosphorylation of IRF3 and production of IP-10. These results identify a novel mechanism by which cigarette smoke exposure impairs antiviral responses in lung epithelial cells, which may contribute to increased susceptibility to respiratory infections.
Control of appetite, blood glucose, and blood pressure during melanocortin-4 receptor activation in normoglycemic and diabetic NPY-deficient mice
Authors: da Silva Alexandre A. , Freeman J. Nathan , Hall John E. , do Carmo Jussara M.
Published: January 2018

Although central melanocortin 4 receptor (MC4R) blockade abolishes the central nervous system (CNS)-mediated anorexogenic, antidiabetic, and cardiovascular actions of leptin, chronic MC4R stimulation fails to completely mimic the effects of leptin. Because neuropeptide Y (NPY) and MC4R exert opposite effects on cardiovascular and metabolic functions, we tested the role of NPY in offsetting the long-term actions of MC4R activation. Wild-type (WT) and NPY-deficient (NPY−/−) mice were implanted with telemetry probes for measuring mean arterial pressure (MAP) and heart rate (HR) 24 h/day. After the mice recovered from surgery and stable baseline measurements, the MC3/4R agonist melanotan II (MTII, 120 μg·kg−1·day−1 iv) was infused for 7 days followed by a recovery period. No major differences between groups were observed at baseline except for slightly higher food intake and HR in NPY−/− mice (4.3 ± 0.2 vs. 3.4 ± 0.2 g/day and 567 ± 14 vs. 522 ± 13 beats/min). Chronic MTII infusion reduced food intake in both groups while causing transient increases in MAP and HR only in WT mice (peaks of 11 ± 3 mmHg and 126 ± 13 beats/min). To examine whether NPY deficiency would amplify the antidiabetic effects of MC4R activation, diabetes was induced with streptozotocin (STZ) 1 wk before baseline measurements were taken, and the same experimental protocol was followed. In WT and NPY−/− mice, STZ-induced diabetes led to similar hyperphagia, hyperglycemia, and weight loss, which were not reversed by chronic MTII treatment. Our results demonstrate that chronic MC4R activation, even in NPY-deficient mice, does not mimic chronic antidiabetic, cardiovascular, or metabolic actions of leptin, and that NPY is not essential for hyperphagia or cardiovascular changes associated with diabetes.
Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy
Authors: Cao Qi , Wang Yiping , Wang Changqi , Wang Xin M. , Lee Vincent W. S. , Zheng Guoping , Zhao Ye , Alexander Stephen I. , Harris David C. H.
Published: January 2018

Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.
Divergent roles for kidney proximal tubule and granulocyte PAD4 in ischemic AKI
Authors: Li Hongmei , Han Sang Jun , Kim Mihwa , Cho Ahyeon , Choi Yewoon , D’Agati Vivette , Lee H. Thomas
Published: January 2018

We previously demonstrated that kidney peptidylarginine deiminase-4 (PAD4) plays a critical role in ischemic acute kidney injury (AKI) in mice by promoting renal tubular inflammation and neutrophil infiltration (Ham A, Rabadi M, Kim M, Brown KM, Ma Z, D’Agati V, Lee HT. Am J Physiol Renal Physiol 307: F1052–F1062, 2014). Although the role of PAD4 in granulocytes including neutrophils is well known, we surprisingly observed profound renal proximal tubular PAD4 induction after renal ischemia-reperfusion (I/R) injury. Here we tested the hypothesis that renal proximal tubular PAD4 rather than myeloid-cell lineage PAD4 plays a critical role in exacerbating ischemic AKI by utilizing mice lacking PAD4 in renal proximal tubules (PAD4ffPEPCK Cre mice) or in granulocytes (PAD4ffLysM Cre mice). Mice lacking renal proximal tubular PAD4 were significantly protected against ischemic AKI compared with wild-type (PAD4ff) mice. Surprisingly, mice lacking PAD4 in myeloid cells were also protected against renal I/R injury although this protection was less compared with renal proximal tubular PAD4-deficient mice. Renal proximal tubular PAD4-deficient mice had profoundly reduced renal tubular apoptosis, whereas myeloid-cell PAD4-deficient mice showed markedly reduced renal neutrophil infiltration. Taken together, our studies suggest that both renal proximal tubular PAD4 as well as myeloid-cell lineage PAD4 play a critical role in exacerbating ischemic AKI. Renal proximal tubular PAD4 appears to contribute to ischemic AKI by promoting renal tubular apoptosis, whereas myeloid-cell PAD4 is preferentially involved in promoting neutrophil infiltration to the kidney and inflammation after renal I/R.
AltitudeOmics: effect of reduced barometric pressure on detection of intrapulmonary shunt, pulmonary gas exchange efficiency, and total pulmonary resistance
Authors: Petrassi Frank A. , Davis James T. , Beasley Kara M. , Evero Oghenero , Elliott Jonathan E. , Goodman Randall D. , Futral Joel E. , Subudhi Andrew , Solano-Altamirano J. Manuel , Goldman Saul , Roach Robert C. , Lovering Andrew T.
Published: January 2018

Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) occurs in healthy humans at rest and during exercise when breathing hypoxic gas mixtures at sea level and may be a source of right-to-left shunt. However, at high altitudes, QIPAVA is reduced compared with sea level, as detected using transthoracic saline contrast echocardiography (TTSCE). It remains unknown whether the reduction in QIPAVA (i.e., lower bubble scores) at high altitude is due to a reduction in bubble stability resulting from the lower barometric pressure (PB) or represents an actual reduction in QIPAVA. To this end, QIPAVA, pulmonary artery systolic pressure (PASP), cardiac output (QT), and the alveolar-to-arterial oxygen difference (AaDO2) were assessed at rest and during exercise (70–190 W) in the field (5,260 m) and in the laboratory (1,668 m) during four conditions: normobaric normoxia (NN; [Formula: see text] = 121 mmHg, PB = 625 mmHg; n = 8), normobaric hypoxia (NH; [Formula: see text] = 76 mmHg, PB = 625 mmHg; n = 7), hypobaric normoxia (HN; [Formula: see text] = 121 mmHg, PB = 410 mmHg; n = 8), and hypobaric hypoxia (HH; [Formula: see text] = 75 mmHg, PB = 410 mmHg; n = 7). We hypothesized QIPAVA would be reduced during exercise in isooxic hypobaria compared with normobaria and that the AaDO2 would be reduced in isooxic hypobaria compared with normobaria. Bubble scores were greater in normobaric conditions, but the AaDO2 was similar in both isooxic hypobaria and normobaria. Total pulmonary resistance (PASP/QT) was elevated in HN and HH. Using mathematical modeling, we found no effect of hypobaria on bubble dissolution time within the pulmonary transit times under consideration (<5 s). Consequently, our data suggest an effect of hypobaria alone on pulmonary blood flow.

NEW & NOTEWORTHY Blood flow through intrapulmonary arteriovenous anastomoses, detected by transthoracic saline contrast echocardiography, was reduced during exercise in acute hypobaria compared with normobaria, independent of oxygen tension, whereas pulmonary gas exchange efficiency was unaffected. Modeling the effect(s) of reduced air density on contrast bubble lifetime did not result in a significantly reduced contrast stability. Interestingly, total pulmonary resistance was increased by hypobaria, independent of oxygen tension, suggesting that pulmonary blood flow may be changed by hypobaria.
The effects of age and sex on mechanical ventilatory constraint and dyspnea during exercise in healthy humans
Authors: Molgat-Seon Yannick , Dominelli Paolo B. , Ramsook Andrew H. , Schaeffer Michele R. , Molgat Sereacki Stéfan , Foster Glen E. , Romer Lee M. , Road Jeremy D. , Guenette Jordan A. , Sheel A. William
Published: January 2018

We examined the effects of age, sex, and their interaction on mechanical ventilatory constraint and dyspnea during exercise in 22 older (age = 68 ± 1 yr; n = 12 women) and 22 younger (age = 25 ± 1 y, n = 11 women) subjects. During submaximal exercise, older subjects had higher end-inspiratory (EILV) and end-expiratory (EELV) lung volumes than younger subjects (both P < 0.05). During maximal exercise, older subjects had similar EILV ( P > 0.05) but higher EELV than younger subjects ( P < 0.05). No sex differences in EILV or EELV were observed. We noted that women had a higher work of breathing (Wb) for a given minute ventilation (V̇e) ≥65 l/min than men ( P < 0.05) and older subjects had a higher Wb for a given V̇e ≥60 l/min ( P < 0.05). No sex or age differences in Wb were present at any submaximal relative V̇e. At absolute exercise intensities, older women experienced expiratory flow limitation (EFL) more frequently than older men ( P < 0.05), and older subjects were more likely to experience EFL than younger subjects ( P < 0.05). At relative exercise intensities, women and older individuals experienced EFL more frequently than men and younger individuals, respectively (both P < 0.05). There were significant effects of age, sex, and their interaction on dyspnea intensity during exercise at absolute, but not relative, intensities (all P < 0.05). Across subjects, dyspnea at 80 W was significantly correlated with indexes of mechanical ventilatory constraint (all P < 0.05). Collectively, our findings suggest age and sex have significant impacts on Wb, operating lung volumes, EFL, and dyspnea during exercise. Moreover, it appears that mechanical ventilatory constraint may partially explain sex differences in exertional dyspnea in older individuals.

NEW & NOTEWORTHY We found that age and sex have a significant effect on mechanical ventilatory constraint and the perception of dyspnea during exercise. We also observed that the perception of exertional dyspnea is associated with indexes of mechanical ventilatory constraint. Collectively, our results suggest that the combined influences of age and biological sex on mechanical ventilatory constraint during exercise contributes, in part, to the increased perception of dyspnea during exercise in older women.
Voluntary exercise slows breast tumor establishment and reduces tumor hypoxia in ApoE−/− mice
Authors: Buss Linda A. , Dachs Gabi U.
Published: January 2018

Exercise reduces the risk of breast cancer development and improves survival in breast cancer patients. However, the underlying mechanisms of this protective effect remain to be fully elucidated, and it is unclear whether exercise can attenuate the protumor effects of obesity and related hyperlipidemia on breast cancer growth and development. We hypothesized that exercise attenuates the negative effect of hyperlipidemia through normalization of the tumor microenvironment and improved T cell infiltrate. Hyperlipidemic ApoE−/− mice with orthotopic EO771 breast tumors were randomly assigned to one of two voluntary running groups or sedentary controls, and muscular cytochrome c oxidase subunit IV (COX-IV) expression was used as a biomarker for the level of exercise. Tumors from mice with high muscular COX-IV expression took significantly longer to reach 100 mm3 ( P = 0.008), but showed no difference in growth rate once the tumor was established. Wheel running appeared to reduce internal metastases, but did not affect T cell infiltrate or the proportion of regulatory and cytotoxic T cells within the tumor. Serum levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased by tumor burden ( P = 0.02) and correlated with spleen weight ( P < 0.0001, R = 0.65). Furthermore, tumor hypoxia was significantly decreased in mice with high muscular COX-IV expression ( P = 0.01). Taken together, these results indicate that wheel running can slow the establishment of primary and secondary EO771 breast tumors and induce beneficial changes in the breast tumor microenvironment in ApoE−/− mice.

NEW & NOTEWORTHY In this first study to investigate the effect of exercise on tumor behavior in a hyperlipidemic model, we hypothesized that wheel running would counteract the protumorigenic environment generated by hyperlipidemia. Wheel running slowed establishment of primary and secondary tumors and reduced tumor hypoxia but did not affect exponential tumor growth in ApoE−/− mice. Overall, voluntary wheel running induced favorable microenvironmental changes in breast tumors.
Effects of −12° head-down tilt with and without elevated levels of CO2 on cognitive performance: the SPACECOT study
Authors: Basner Mathias , Nasrini Jad , Hermosillo Emanuel , McGuire Sarah , Dinges David F. , Moore Tyler M. , Gur Ruben C. , Rittweger Jörn , Mulder Edwin , Wittkowski Martin , Donoviel Dorit , Stevens Brian , Bershad Eric M. ,   the SPACECOT Investigator Group
Published: January 2018

Microgravity and elevated levels of CO2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2 concentrations during 26.5-h periods of −12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (−0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO2 levels. There were no statistically significant time-in-CO2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies.

NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of −12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO2 concentrations to 0.5%.
Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes
Authors: Song Yejia , Belardinelli Luiz
Published: January 2018

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na+ current ( INaL); and 3) inhibition of INaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H2O2). Experiments were performed on ventricular myocytes isolated from (young) 1-mo- and (old) 1-yr-old guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the INaL inhibitors GS967 and tetrodotoxin. The magnitude of INaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the NaV1.5-channel blocker methanethiosulfonate ethylammonium blocked the INaL. There were no significant differences between myocytes from young and old GPs in L-type Ca2+ current and the rapidly and slowly activating delayed rectifier K+ currents, although the inward rectifier K+ current was slightly decreased in myocytes from old GPs. H2O2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H2O2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in NaV1.5-channel INaL is responsible for the prolongation of APD, and 3) inhibition of INaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

NEW & NOTEWORTHY The action potential duration is significantly longer in ventricular myocytes from old than from young guinea pigs, which may explain, at the cellular level, the increase in QT interval with age. A CaMKII-mediated enhancement of NaV1.5-channel late current is responsible for the age-related prolongation of action potential duration. The enhanced basal late sodium current may predispose cardiac myocytes of old animals to oxidative stress and arrhythmogenesis.
Real-time particle filtering and smoothing algorithms for detecting abrupt changes in neural ensemble spike activity
Authors: Hu Sile , Zhang Qiaosheng , Wang Jing , Chen Zhe
Published: January 2018

Sequential change-point detection from time series data is a common problem in many neuroscience applications, such as seizure detection, anomaly detection, and pain detection. In our previous work (Chen Z, Zhang Q, Tong AP, Manders TR, Wang J. J Neural Eng 14: 036023, 2017), we developed a latent state-space model, known as the Poisson linear dynamical system, for detecting abrupt changes in neuronal ensemble spike activity. In online brain-machine interface (BMI) applications, a recursive filtering algorithm is used to track the changes in the latent variable. However, previous methods have been restricted to Gaussian dynamical noise and have used Gaussian approximation for the Poisson likelihood. To improve the detection speed, we introduce non-Gaussian dynamical noise for modeling a stochastic jump process in the latent state space. To efficiently estimate the state posterior that accommodates non-Gaussian noise and non-Gaussian likelihood, we propose particle filtering and smoothing algorithms for the change-point detection problem. To speed up the computation, we implement the proposed particle filtering algorithms using advanced graphics processing unit computing technology. We validate our algorithms, using both computer simulations and experimental data for acute pain detection. Finally, we discuss several important practical issues in the context of real-time closed-loop BMI applications.

NEW & NOTEWORTHY Sequential change-point detection is an important problem in closed-loop neuroscience experiments. This study proposes novel sequential Monte Carlo methods to quickly detect the onset and offset of a stochastic jump process that drives the population spike activity. This new approach is robust with respect to spike sorting noise and varying levels of signal-to-noise ratio. The GPU implementation of the computational algorithm allows for parallel processing in real time.
Location and phase effects for ocular and cervical vestibular-evoked myogenic potentials evoked by bone-conducted stimuli at midline skull sites
Authors: Govender Sendhil , Colebatch James G.
Published: January 2018

Our object was to investigate the effect of location and phase on the properties of oVEMPs and cVEMPs evoked by two bone conducted (BC) stimuli, 500 Hz and an impulsive stimulus for midline skull sites from Nz to Iz, in normal volunteers. Compressive and rarefactive onset phases were used and the induced linear and rotational accelerations measured. We confirmed our previous finding of marked changes in the polarity of oVEMPs with location. For cVEMPs using the 500Hz stimulus there were few changes with location or phase, but the impulsive stimulus showed clear phase-related changes at several locations, with the shortest latencies occurring with compressive stimuli at AFz and Fz and the largest amplitudes at Iz. For oVEMPs, both stimuli showed clear effects of phase, with the shortest latencies with compressive stimuli at AFz and Fz and with the largest negativity at Oz or Iz. Whereas the effectiveness at Iz is consistent with a role in the linear VOR, the inversion of polarity and shorter latency around AFz and Fz is not and could not be explained by changes in acceleration of the head. The latency for BC 500Hz oVEMPs for AFz was the same as that for air-conducted (AC) stimuli. We suggest that whereas BC stimuli at most sites work through displacement of the otolith membrane, BC oVEMPs evoked at AFz and Fz may work through a direct action on utricular hair cells. Our findings have implications for clinical testing of VEMPs using midline BC stimuli.

NEW & NOTEWORTHY We investigated VEMPs evoked from multiple midline skull sites. Large oVEMP responses were obtained with compressive stimuli at Iz, consistent with a role in the linear VOR, but we also showed inversion of polarity and the shortest latency for stimuli given at AFz and Fz. We propose that BC stimuli given at AFz and Fz may have a direct effect on otolith hair cells, whereas at other sites they work through displacement of the otolith membrane.
Identifying low-grade cellular rejection after heart transplantation in children by using gene expression profiling
Authors: Xin Annie , Lee Melissa G. Y. , Hu Yifang , Ignjatovic Vera , Shi William Y. , Shipp Anne , Praporski Slavica , Kallies Axel , Weintraub Robert G. , Monagle Paul T. , Smyth Gordon K. , Konstantinov Igor E.
Published: January 2018

Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by using global gene expression profiling in blood. A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011 to 2014 were analyzed (18 baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in 10% (9/88). mRNA from each sample was sequenced. Differential expression analysis was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied to the most differentially expressed (DE) genes to identify rejection after transplantation. Mean age at transplantation was 10.0 ± 5.4 yr. Expression of B cell and T cell receptor sequences was used to measure the effect of posttransplantation immunosuppression. Follow-up samples had lower levels of immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower numbers of activated B cells). T cell receptor alpha and beta gene families had decreased expression in 0R samples compared with pretransplantation ( P < 4E-5) but recovered to near baseline levels in 1R/2R samples. kNN using the most DE gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R compared with 0R by leave-one-out cross validation. Using a genomic approach we can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection (0R) after heart transplantation in children despite a wide age range.
Boundary Control of a Flexible Manipulator Based on a High Order Disturbance Observer with Input Saturation
Authors: Ma Junteng , Jin Dongping , Wei Zhengtao , Chen Ti , Wen Hao
Published: January 2018

This paper studies a new boundary control strategy for a flexible manipulator subject to unknown fast time‐varying disturbances. The flexible manipulator essentially is an infinite dimensional continuum. Hence, a continuous function of space and time can be employed to describe the position of such a distributed parameter structure, the motion of which can be described by partial differential equations (PDEs). To cope with fast time‐varying external disturbances, a high order disturbance observer is adopted. A control strategy based on such a disturbance observer is proposed for the rest‐rest maneuvering of the flexible manipulator. Moreover, a smooth hyperbolic function is included in the controller to satisfy the requirement of input saturation. The stability of the boundary control is analyzed using LaSalle’s invariance principle. Finally, the performance of the presented boundary controller is verified through comparison with that of employing a constant disturbance observer via numerical simulations.
Acute Primary Adrenal Insufficiency after Hip Replacement in a Patient with Acute Intermittent Porphyria
Authors: Latina Adele , Terzolo Massimo , Pia Anna , Reimondo Giuseppe , Castellano Elena , Pellegrino Micaela , Borretta Giorgio
Published: January 2018

Adrenal insufficiency is a potentially life-threatening condition when it occurs acutely, as in adrenal hemorrhage. Generally it is not reversible and requires chronic replacement therapy. Acute intermittent porphyria (AIP) is a rare genetic disease characterized by alterations in heme biosynthesis that result in accumulation of precursors in tissues. A crisis can be triggered by many conditions such as surgery and infections. Symptoms are similar to those of acute hypoadrenalism. Moreover, both conditions are characterized by hyponatremia. We describe the case of a postmenopausal woman known to be affected by AIP who developed after surgery a primary adrenal insufficiency associated with adrenal enlargement; the latter completely reverted in six months.