bluuebunny/crossref_metadata_2025 huggingface dataset:
COARSE SPACES BY ALGEBRAIC MULTIGRID: MULTIGRID CONVERGENCE AND UPSCALING ERROR ESTIMATES
Authors: VASSILEVSKI PANAYOT S.
Published: September 2011

We give an overview of a number of algebraic multigrid methods targeting finite element discretization problems. The focus is on the properties of the constructed hierarchy of coarse spaces that guarantee (two-grid) convergence. In particular, a necessary condition known as "weak approximation property," and a sufficient one, referred to as "strong approximation property," are discussed. Their role in proving convergence of the TG method (as iterative method) and also on the approximation properties of the algebraic mottigrid (AMG) coarse spaces if used as discretization tool is pointed out. Some preliminary numerical results illustrating the latter aspect are also reported.
AN ENERGY-CONSERVING DISCONTINUOUS MULTISCALE FINITE ELEMENT METHOD FOR THE WAVE EQUATION IN HETEROGENEOUS MEDIA
Authors: CHUNG ERIC T. , EFENDIEV YALCHIN , GIBSON RICHARD L.
Published: September 2011

Seismic data are routinely used to infer in situ properties of earth materials on many scales, ranging from global studies to investigations of surficial geological formations. While inversion and imaging algorithms utilizing these data have improved steadily, there are remaining challenges that make detailed measurements of the properties of some geologic materials very difficult. For example, the determination of the concentration and orientation of fracture systems is prohibitively expensive to simulate on the fine grid and, thus, some type of coarse-grid simulations are needed. In this paper, we describe a new multiscale finite element algorithm for simulating seismic wave propagation in heterogeneous media. This method solves the wave equation on a coarse grid using multiscale basis functions and a global coupling mechanism to relate information between fine and coarse grids. Using a mixed formulation of the wave equation and staggered discontinuous basis functions, the proposed multiscale methods have the following properties.

• The total wave energy is conserved.

• Mass matrix is diagonal on a coarse grid and explicit energy-preserving time discretization does not require solving a linear system at each time step.

• Multiscale basis functions can accurately capture the subgrid variations of the solution and the time stepping is performed on a coarse grid.

We discuss various subgrid capturing mechanisms and present some preliminary numerical results.
Role of caveolin-1 in endothelial BKCa channel regulation of vasoreactivity
Authors: Riddle Melissa A. , Hughes Jennifer M. , Walker Benjimen R.
Published: September 2011

A novel vasodilatory influence of endothelial cell (EC) large-conductance Ca2+-activated K+ (BKCa) channels is present following in vivo exposure to chronic hypoxia (CH) and may exist in other pathological states. However, the mechanism of channel activation that results in altered vasoreactivity is unknown. We tested the hypothesis that CH removes an inhibitory effect of the scaffolding domain of caveolin-1 (Cav-1) on EC BKCa channels to permit activation, thereby affecting vasoreactivity. Experiments were performed on gracilis resistance arteries and ECs from control and CH-exposed (380 mmHg barometric pressure for 48 h) rats. EC membrane potential was hyperpolarized in arteries from CH-exposed rats and arteries treated with the cholesterol-depleting agent methyl-β-cyclodextrin (MBCD) compared with controls. Hyperpolarization was reversed by the BKCa channel antagonist iberiotoxin (IBTX) or by a scaffolding domain peptide of Cav-1 (AP-CAV). Patch-clamp experiments documented an IBTX-sensitive current in ECs from CH-exposed rats and in MBCD-treated cells that was not present in controls. This current was enhanced by the BKCa channel activator NS-1619 and blocked by AP-CAV or cholesterol supplementation. EC BKCa channels displayed similar unitary conductance but greater Ca2+ sensitivity than BKCa channels from vascular smooth muscle. Immunofluorescence imaging demonstrated greater association of BKCa α-subunits with Cav-1 in control arteries than in arteries from CH-exposed rats, although fluorescence intensity for each protein did not differ between groups. Finally, AP-CAV restored myogenic and phenylephrine-induced constriction in arteries from CH-exposed rats without affecting controls. AP-CAV similarly restored diminished reactivity to phenylephrine in control arteries pretreated with MBCD. We conclude that CH unmasks EC BKCa channel activity by removing an inhibitory action of the Cav-1 scaffolding domain that may depend on cellular cholesterol levels.
Low-magnitude whole body vibration with resistive exercise as a countermeasure against cardiovascular deconditioning after 60 days of head-down bed rest
Authors: Coupé Mickael , Yuan Ming , Demiot Claire , Bai Yanqiang Q. , Jiang Shizhong Z. , Li Yongzhi Z. , Arbeille Philippe , Gauquelin-Koch Guillemette , Levrard Thibaud , Custaud Marc-Antoine , Li Yinghui H.
Published: September 2011

Whole body vibration with resistive exercise is a promising countermeasure against some weightlessness-induced dysfunctions. Our objective was to study whether the combination of low-magnitude whole body vibration with a resistive exercise can prevent the cardiovascular deconditioning induced by a nonstrict 60-day head-down bed rest (Earth Star International Bed Rest Experiment Project). Fourteen healthy men participated in this study. We recorded electrocardiograms and blood pressure waves by means of a noninvasive beat-by-beat measurement system (Cardiospace, integrated by Centre National d'Etudes Spatiales and Astronaut Center of China) during an orthostatic test (20 min of 75-degree head-up tilt test) before and immediately after bed rest. We estimated heart rate, blood pressure, cardiac output, stroke volume, total peripheral resistance, baroreflex sensitivity, and heart rate variability. Low-magnitude whole body vibration with resistive exercise prevented an increase of the sympathetic index (reflecting the sympathovagal balance of cardiac autonomic control) and limited the decrease of the spontaneous baroreflex sensitivity induced by 60 days of head-down bed rest. However, this countermeasure had very little effect on cardiac hemodynamics and did not improve the orthostatic tolerance. This combined countermeasure did not efficiently prevent orthostatic intolerance but prevents changes in the autonomic nervous system associated with cardiovascular deconditioning. The underlying mechanisms remain hypothetical but might involve cutaneous and muscular mechanoreceptors.
Distension of the uterus induces HspB1 expression in rat uterine smooth muscle
Authors: White B. G. , MacPhee D. J.
Published: September 2011

The uterine musculature, or myometrium, demonstrates tremendous plasticity during pregnancy under the influences of the endocrine environment and mechanical stresses. Expression of the small stress protein heat shock protein B1 (HspB1) has been reported to increase dramatically during late pregnancy, a period marked by myometrial hypertrophy caused by fetal growth-induced uterine distension. Thus, using unilaterally pregnant rat models and ovariectomized nonpregnant rats with uteri containing laminaria tents to induce uterine distension, we examined the effect of uterine distension on myometrial HspB1 expression. In unilaterally pregnant rats, HspB1 mRNA and Ser15-phosphorylated HspB1 (pSer15HspB1) protein expression were significantly elevated in distended gravid uterine horns at days 19 and 23 (labor) of gestation compared with nongravid horns. Similarly, pSer15HspB1 protein in situ was only readily detectable in the distended horns compared with the nongravid horns at days 19 and 23; however, pSer15HspB1 was primarily detectable in situ at day 19 in membrane-associated regions, while it had primarily a cytoplasmic localization in myometrial cells at day 23. HspB1 mRNA and pSer15HspB1 protein expression were also markedly increased in ovariectomized nonpregnant rat myometrium distended for 24 h with laminaria tents compared with empty horns. Therefore, uterine distension plays a major role in the stimulation of myometrial HspB1 expression, and increased expression of this small stress protein could be a mechanoadaptive response to the increasing uterine distension that occurs during pregnancy.
Central stiffening in adulthood linked to aberrant aortic remodeling under suboptimal intrauterine conditions
Authors: Thompson Jennifer A. , Gros Robert , Richardson Bryan S. , Piorkowska Karolina , Regnault Timothy R. H.
Published: September 2011

This study examined perturbed aortic development and subsequent wall stiffening as a link to later cardiovascular disease. Placental insufficiency was induced in pregnant guinea pigs at midgestation by uterine artery ligation. Near term, fetuses were killed and defined as normal birth weight (NBW), low birth weight (LBW), and intrauterine growth restricted (IUGR). Offspring were classified according to birth weight and killed in adulthood. Collagen and elastin content of aortas were analyzed using Sirius red and orcein staining, respectively. Immunofluorescence was used for detection of α-actin and nonmuscle myosin heavy chain (MHC-B), a marker of synthetic-type vascular smooth muscle cells (VSMCs). Ex vivo generation of length-tension curves was performed with aortic rings from adult offspring. Relative elastic fiber content was decreased by 10% in LBW and 14% in IUGR compared with NBW fetuses. In adulthood, relative elastic fiber content was 51% lower in LBW vs. NBW, and the number of elastic laminae adjusted for wall thickness was 25% lower in LBW ( P < 0.01). The percent area stained for MHC-B was sixfold higher in LBW vs. NBW fetuses ( P < 0.0001) and threefold higher in LBW vs. NBW adult offspring ( P < 0.05). The increase in MHC-B in LBW offspring concurred with a 41% increase in total collagen content and a 33 and 56% increase in relative and total α-actin content, respectively ( P < 0.05). Thus aortic wall stiffening in adulthood can be traced to altered matrix composition established under suboptimal intrauterine conditions that is amplified postnatally by the activity of synthetic VSMCs.
Recovery of baroreflex control of renal sympathetic nerve activity after spinal lesions in the rat
Authors: Zahner Matthew R. , Kulikowicz Ewa , Schramm Lawrence P.
Published: September 2011

Spinal cord injury (SCI) has serious long-term consequences on sympathetic cardiovascular regulation. Orthostatic intolerance results from insufficient baroreflex regulation (BR) of sympathetic outflow to maintain proper blood pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient inhibition of spinal sources of sympathetic activity. Both of these conditions result from the inability to control sympathetic activity caudal to SCI. It is well established that limited motor ability recovers after incomplete SCI. Therefore, the goal of this study was to determine whether recovery of BR occurs after chronic, left thoracic spinal cord hemisection at either T3 or T8. Baroreflex tests were performed in rats by measuring the reflex response of left (ipsilateral) renal sympathetic nerve activity to decreases and increases in arterial pressure produced by ramped infusions of sodium nitroprusside and phenylephrine, respectively. One week after a T3 left hemisection, BR function was modestly impaired. However, 8 wk after a T3 left hemisection, BR function was normal. One week after a T8 left hemisection, BR function was significantly impaired, and 8 wk after a T8 left hemisection, BR function was significantly improved. These results indicate that BR of renal sympathetic nerve activity in rats may partially recover after spinal cord hemisections, becoming normal by 8 wk after a T3 lesion, but not after a T8 lesion. The nature of the spinal cord and/or brain stem reorganization that mediates this recovery remains to be determined.
Sepsis-induced alterations in sleep of rats
Authors: Baracchi Francesca , Ingiosi Ashley M. , Raymond Richard M. , Opp Mark R.
Published: September 2011

Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions.
Endogenous modulation of low frequency oscillations by temporal expectations
Authors: Cravo Andre M. , Rohenkohl Gustavo , Wyart Valentin , Nobre Anna C.
Published: September 2011

Recent studies have associated increasing temporal expectations with synchronization of higher frequency oscillations and suppression of lower frequencies. In this experiment, we explore a proposal that low-frequency oscillations provide a mechanism for regulating temporal expectations. We used a speeded Go/No-go task and manipulated temporal expectations by changing the probability of target presentation after certain intervals. Across two conditions, the temporal conditional probability of target events differed substantially at the first of three possible intervals. We found that reactions times differed significantly at this first interval across conditions, decreasing with higher temporal expectations. Interestingly, the power of theta activity (4–8 Hz), distributed over central midline sites, also differed significantly across conditions at this first interval. Furthermore, we found a transient coupling between theta phase and beta power after the first interval in the condition with high temporal expectation for targets at this time point. Our results suggest that the adjustments in theta power and the phase-power coupling between theta and beta contribute to a central mechanism for controlling neural excitability according to temporal expectations.
Individual and synergistic effects of sniffing frequency and flow rate on olfactory bulb activity
Authors: Courtiol Emmanuelle , Hegoburu Chloé , Litaudon Philippe , Garcia Samuel , Fourcaud-Trocmé Nicolas , Buonviso Nathalie
Published: September 2011

Is faster or stronger sniffing important for the olfactory system? Odorant molecules are captured by sniffing. The features of sniffing constrain both the temporality and intensity of the input to the olfactory structures. In this context, it is clear that variations in both the sniff frequency and flow rate have a major impact on the activation of olfactory structures. However, the question of how frequency and flow rate individually or synergistically impact bulbar output has not been answered. We have addressed this question using multiple experimental approaches. In double-tracheotomized, anesthetized rats, we recorded both the bulbar local field potential (LFP) and mitral/tufted cells' activities when the sampling flow rate and frequency were controlled independently. We found that a tradeoff between the sampling frequency and the flow rate could maintain olfactory bulb sampling-related rhythmicity and that only an increase in flow rate could induce a faster, odor-evoked response. LFP and sniffing were recorded in awake rats. We found that sampling-related rhythmicity was maintained during high-frequency sniffing. Furthermore, we observed that the covariation between the frequency and flow rate, which was necessary for the tradeoff seen in the anesthetized preparations, also occurred in awake animals. Our study shows that the sampling frequency and flow rate can act either independently or synergistically on bulbar output to shape the neuronal message. The system likely takes advantage of this flexibility to adapt sniffing strategies to animal behavior. Our study provides additional support for the idea that sniffing and olfaction function in an integrated manner.
Flexible interpretation of a decision rule by supplementary eye field neurons
Authors: Heinen S. J. , Hwang H. , Yang S. N.
Published: September 2011

Since the environment is in constant flux, decision-making capabilities of the brain must be rapid and flexible. Yet in sensory motion processing pathways of the primate brain where decision making has been extensively studied, the flexibility of neurons is limited by inherent selectivity to motion direction and speed. The supplementary eye field (SEF), an area involved in decision making on moving stimuli, is not strictly a sensory or motor structure, and hence may not suffer such limitations. Here we test whether neurons in the SEF can flexibly interpret the rule of a go/nogo task when the decision boundary in the task changes with each trial. The task rule specified that the animal pursue a moving target with its eyes if and when the target entered a visible zone. The size of the zone was changed from trial to trial in order to shift the decision boundary, and thereby assign different go/nogo significance to the same motion trajectories. Individual SEF neurons interpreted the rule appropriately, signaling go or nogo in compliance with the rule and not the direction of motion. The results provide the first evidence that individual neurons in frontal cortex can flexibly interpret a rule that governs the decision to act.
Design of Intelligent Self‐Tuning GA ANFIS Temperature Controller for Plastic Extrusion System
Authors: Ravi S. , Sudha M. , Balakrishnan P. A.
Published: September 2011

This paper develops a GA ANFIS controller design method for temperature control in plastic extrusion system. Temperature control of plastic extrusion system suffers problems related to longer settling time, couple effects, large time constants, and undesirable overshoot. The system is generally nonlinear and the temperature of the plastic extrusion system may vary over a wide range of disturbances. The system is designed with three controllers. The proposed GA ANFIS controller is the most powerful approach to retrieve the adaptiveness in the case of nonlinear system. In this research the control methods are simulated using simulink. Relatively the methodology and efficiency of the proposed method are compared with those of the traditional methods and the results obtained from GA ANFIS controller give improved performance in terms of time domain specification, set point tracking, and disturbance rejection with optimum stability.
Robust Decentralized Formation Flight Control
Authors: Weihua Zhao , Go Tiauw Hiong
Published: September 2011

Motivated by the idea of multiplexed model predictive control (MMPC), this paper introduces a new framework for unmanned aerial vehicles (UAVs) formation flight and coordination. Formulated using MMPC approach, the whole centralized formation flight system is considered as a linear periodic system with control inputs of each UAV subsystem as its periodic inputs. Divided into decentralized subsystems, the whole formation flight system is guaranteed stable if proper terminal cost and terminal constraints are added to each decentralized MPC formulation of the UAV subsystem. The decentralized robust MPC formulation for each UAV subsystem with bounded input disturbances and model uncertainties is also presented. Furthermore, an obstacle avoidance control scheme for any shape and size of obstacles, including the nonapriorily known ones, is integrated under the unified MPC framework. The results from simulations demonstrate that the proposed framework can successfully achieve robust collision-free formation flights.
Arenavirus Budding
Authors: Urata Shuzo , de la Torre Juan Carlos
Published: September 2011

Several arenaviruses cause hemorrhagic fever disease in humans and pose a significant public health concern in their endemic regions. On the other hand, the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus-host interactions and associated disease. The arenavirus small RING finger protein called Z has been shown to be the main driving force of virus budding. The budding activity of Z is mediated by late (L) domain motifs, PT/SAP, and PPXY, located at the C-terminus of Z. This paper will present the current knowledge on arenavirus budding including the diversity of L domain motifs used by different arenaviruses. We will also discuss how improved knowledge of arenavirus budding may facilitate the development of novel antiviral strategies to combat human pathogenic arenaviruses.
Aeolian Sediment Transport Integration in General Stratigraphic Forward Modeling
Authors: Salles T. , Griffiths C. , Dyt C.
Published: September 2011

A large number of numerical models have been developed to simulate the physical processes involved in saltation, and, recently to investigate the interaction between soil vegetation cover and aeolian transport. These models are generally constrained to saltation of monodisperse particles while natural saltation occurs over mixed soils. We present a three-dimensional numerical model of steady-state saltation that can simulate aeolian erosion, transport and deposition for unvegetated mixed soils. Our model simulates the motion of saltating particles using a cellular automata algorithm. A simple set of rules is used and takes into account an erosion formula, a transport model, a wind exposition function, and an avalanching process. The model is coupled to the stratigraphic forward model Sedsim that accounts for a larger number of geological processes. The numerical model predicts a wide range of typical dune shapes, which have qualitative correspondence to real systems. The model reproduces the internal structure and composition of the resulting aeolian deposits. It shows the complex formation of dune systems with cross-bedding strata development, bounding surfaces overlaid by fine sediment and inverse grading deposits. We aim to use it to simulate the complex interactions between different sediment transport processes and their resulting geological morphologies.
Integrating Independent Component Analysis and Principal Component Analysis with Neural Network to Predict Chinese Stock Market
Authors: Liu Haifan , Wang Jun
Published: September 2011

We investigate the statistical behaviors of Chinese stock market fluctuations
by independent component analysis. The independent component analysis (ICA)
method is integrated into the neural network model. The proposed approach uses
ICA method to analyze the input data of neural network and can obtain the latent
independent components (ICs). After analyzing and removing the IC that represents
noise, the rest of ICs are used as the input of neural network. In order to forect
the fluctuations of Chinese stock market, the data of Shanghai Composite Index is
selected and analyzed, and we compare the forecasting performance of the proposed
model with those of common BP model integrating principal component analysis
(PCA) and single BP model. Experimental results show that the proposed model
outperforms the other two models no matter in relatively small or relatively large
sample, and the performance of BP model integrating PCA is closer to that of the proposed
model in relatively large sample. Further, the prediction results on the points where
the prices fluctuate violently by the above three models relatively deviate from the
corresponding real market data.
Nonemptiness and Compactness of Solutions Set for Nondifferentiable Multiobjective Optimization Problems
Authors: Wu Xin-kun , Chen Jia-wei , Zou Yun-zhi
Published: September 2011

A nondifferentiable multiobjective optimization problem with nonempty set constraints is considered, and the equivalence of weakly efficient solutions, the critical points for the nondifferentiable multiobjective optimization problems, and solutions for vector variational‐like inequalities is established under some suitable conditions. Nonemptiness and compactness of the solutions set for the nondifferentiable multiobjective optimization problems are proved by using the FKKM theorem and a fixed‐point theorem.
Link Prediction and Route Selection Based on Channel State Detection in UASNs
Authors: Chen Jian , Han Yanyan , Li Deshi , Nie Jugen
Published: September 2011

In Underwater Acoustic Sensor Networks (UASNs), data route is often disrupted by link interruption which will further lead to incorrect data transmission due to high propagation delay, Doppler effect, and the vulnerability of water environment in acoustic channel. So how to correctly transmit data when there are interrupted links on the data path is just the issue Delay Tolerant Networks (DTNs) aim to solve. In this paper, we propose a model to predict link interruption and route interruption in UASNs by the historical link information and channel state obtained by periodic detection. A method of decomposing and recomposing routes hop by hop in order to optimize route reselection is also presented. Moreover, we present a back-up route maintenance scheme to keep back-up routes with fresh information. In case of single route, we advance the idea to utilize the periodicity of environmental changes to help predict link interruption. In the simulation, we make comparisons on node energy consumption, end-to-end delay as well as bit error rate with and without link prediction. It can be derived that the network performance is significantly improved with our mechanism, so that our mechanism is effective and efficient while guaranteeing reliable data transmission.
Alstonia scholarisR. Br. Significantly Inhibits Retinoid-Induced Skin IrritationIn VitroandIn Vivo
Authors: Lee Soo-Jin , Cho Sun-A , An Su-Sun , Na Yong-Joo , Park Nok-Hyun , Kim Han-Sung , Lee Chan-Woo , Kim Han-Kon , Kim Eun-Kyung , Jang Young-Pyo , Kim Jin-Woong
Published: September 2011

Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract ofAlstonia scholarisR. Br. can significantly inhibitall-transretinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed byA. scholarisextract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations)in vitro. In a cumulative irritation patch test,A. scholarisextract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest thatA. scholarisis a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation.
Behaviour of Human Erythrocyte Aggregation in Presence of Autologous Lipoproteins
Authors: Saldanha C. , Loureiro J. , Moreira C. , Silva J. Martins e
Published: September 2011

The aim of this work was to evaluatein vitrothe effect of autologous plasma lipoprotein subfractions on erythrocyte tendency to aggregate. Aliquots of human blood samples were enriched or not (control) with their own HDL-C, LDL-C, or VLDL-C fractions obtained from the same batch by density gradient ultracentrifugation. Plasma osmolality and erythrocyte aggregation index (EAI) were determined. Blood aliquots enriched with LDL-C and HDL-C showed significant higher EAI than untreated aliquots, whereas enrichment with VLDL-C does not induce significant EAI changes. For the same range of lipoprotein concentrations expressed as percentage of osmolality variation, the EAI variation was positive and higher in presence of HDL-C than upon enrichment with LDL-C (P<0.01). Particle size, up to LDL diameter values, seems to reinforce erythrocyte tendency to aggregate at the same plasma osmolality (particle number) range of values.
Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling
Authors: Patterson Andrew D. , Maurhofer Olivier , Beyoğlu Diren , Lanz Christian , Krausz Kristopher W. , Pabst Thomas , Gonzalez Frank J. , Dufour Jean-François , Idle Jeffrey R.
Published: September 2011

There has been limited analysis of the effects of hepatocellular carcinoma (HCC) on liver metabolism and circulating endogenous metabolites. Here, we report the findings of a plasma metabolomic investigation of HCC patients by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), random forests machine learning algorithm, and multivariate data analysis. Control subjects included healthy individuals as well as patients with liver cirrhosis or acute myeloid leukemia. We found that HCC was associated with increased plasma levels of glycodeoxycholate, deoxycholate 3-sulfate, and bilirubin. Accurate mass measurement also indicated upregulation of biliverdin and the fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochol-4,6-dien-24-oic acid in HCC patients. A quantitative lipid profiling of patient plasma was also conducted by ultraperformance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-TQMS). By this method, we found that HCC was also associated with reduced levels of lysophosphocholines and in 4 of 20 patients with increased levels of lysophosphatidic acid [LPA(16:0)], where it correlated with plasma α-fetoprotein levels. Interestingly, when fatty acids were quantitatively profiled by gas chromatography-mass spectrometry (GC-MS), we found that lignoceric acid (24:0) and nervonic acid (24:1) were virtually absent from HCC plasma. Overall, this investigation illustrates the power of the new discovery technologies represented in the UPLC-ESI-QTOFMS platform combined with the targeted, quantitative platforms of UPLC-ESI-TQMS and GC-MS for conducting metabolomic investigations that can engender new insights into cancer pathobiology. Cancer Res; 71(21); 6590–600. ©2011 AACR.
ARID1A, a Factor That Promotes Formation of SWI/SNF-Mediated Chromatin Remodeling, Is a Tumor Suppressor in Gynecologic Cancers
Authors: Guan Bin , Wang Tian-Li , Shih Ie-Ming
Published: September 2011

ARID1A (BAF250A) promotes the formation of SWI/SNF chromatin remodeling complexes containing BRG1 or BRM. It has emerged as a candidate tumor suppressor based on its frequent mutations in ovarian clear cell and endometrioid cancers and in uterine endometrioid carcinomas. Here, we report that restoring wild-type ARID1A expression in ovarian cancer cells that harbor ARID1A mutations is sufficient to suppress cell proliferation and tumor growth in mice, whereas RNA interference–mediated silencing of ARID1A in nontransformed epithelial cells is sufficient to enhance cellular proliferation and tumorigenicity. Gene expression analysis identified several downstream targets of ARID1A including CDKN1A and SMAD3, which are well-known p53 target genes. In support of the likelihood that p53 mediates the effects of ARID1A on these genes, we showed that p53 was required and sufficient for their regulation by ARID1A. Furthermore, we showed that CDKN1A (encoding p21) acted in part to mediate growth suppression by ARID1A. Finally, we obtained evidence that the ARID1A/BRG1 complex interacted directly with p53 and that mutations in the ARID1A and TP53 genes were mutually exclusive in tumor specimens examined. Our results provide functional evidence in support of the hypothesis that ARID1A is a bona fide tumor suppressor that collaborates with p53 to regulate CDKN1A and SMAD3 transcription and tumor growth in gynecologic cancers. Cancer Res; 71(21); 6718–27. ©2011 AACR.
The Impact of Common Genetic Variations in Genes of the Sex Hormone Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer Aggressiveness
Authors: Sun Tong , Oh William K. , Jacobus Susanna , Regan Meredith , Pomerantz Mark , Freedman Matthew L. , Lee Gwo-Shu Mary , Kantoff Philip W.
Published: September 2011

Our previous work suggested that there was no significant association between plasma steroid hormone levels and prostate cancer tumor grade at diagnosis. In this study, we systematically tested the hypothesis that inherited variations in the androgen and estrogen metabolic pathways may be associated with plasma levels of steroid hormones, or prostate cancer aggressiveness at diagnosis. Plasma hormone levels including total testosterone, total estradiol, and sex hormone–binding globulin were measured in a cohort of 508 patients identified with localized prostate cancer. D'Amico risk classification at diagnosis was also determined. A total of 143 single-nucleotide polymorphisms (SNPs) from 30 genes that are involved in androgen and estrogen metabolism were selected for analysis. The global association of genotypes with plasma hormone levels and prostate cancer aggressiveness (D'Amico risk classification) was statistically analyzed. Q values were estimated to account for multiple testing. We observed significant associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151), HSD17B3 (rs9409407), and HSD17B1 (rs12602084), with P values of 0.002, 0.006, and 0.006, respectively. We also observed borderline significant associations between prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005), UGT2B15 (rs2045100; P = 0.007), and HSD17B12 (rs7932905; P = 0.008). No individual SNP was associated with both clinical variables. Genetic variants of genes in hormone metabolic pathways may influence plasma androgen levels or prostate cancer aggressiveness. However, it seems that the inherited variations affecting plasma hormone levels differ from those affecting disease aggressiveness. Cancer Prev Res; 4(12); 2044–50. ©2011 AACR.
Involvement of IRAKs and TRAFs in anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells
Authors: Guo Donglin , Zhou Fang , Chen Dongdong , Xie Hongxiang , Wang Ting , Wang Haibo , Xu Guoying , Wen Haiping , Hong Zhou
Published: September 2011

Our previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β2-glycoprotein I/β2-glycoprotein I (anti-β2GPI/β2GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its downstream molecules have not been well explored. In this study, we have established that interleukin-1 receptor-associated kinases (IRAKs) and tumour necrosis factor receptor-associated factors (TRAFs) are crucial downstream molecules of anti-β2GPI/β2GPI-induced TLR4 signaling pathway in THP-1 cells and explored the potential mechanisms of their self-regulation. Treatment of THP-1 cells with anti-β2GPI/β2GPI complex induced IRAKs and TRAFs expression and activation. Anti-β2GPI/β2GPI complex firstly induced expression of IRAK4 and IRAK1, then IRAK1 phosphorylation and last IRAK3 upregulation. In addition, anti-β2GPI/β2GPI complex simultaneously and acutely enhanced mRNA levels of TRAF6, TRAF4 and zinc finger protein A20 (A20), while chronically increased A20 protein level. Moreover, anti-β2GPI/β2GPI complex-induced IRAKs and TRAFs expression and activation were attenuated by knockdown of ANX2 by infection with ANX2-specific RNA interference lentiviruses (LV-RNAi-ANX2) or by treatment with paclitaxel, which inhibits TLR4 as an antagonist of myeloid differentiation protein 2 (MD-2) ligand. Furthermore, both IRAK1/4 inhibitor and a specific proteasome inhibitor MG-132 could attenuate TRAFs expression as well as TF expression induced by anti-β2GPI/β2GPI complex. In conclusion, our results indicate that IRAKs and TRAFs play important roles in anti-β2GPI/β2GPI-stimulated TLR4/TF signaling pathway in THP-1 cells and contribute to the pathological processes of antiphospholipid syndrome (APS).
Impacts of Land–Atmosphere Feedbacks on Deep, Moist Convection on the Canadian Prairies
Authors: Brimelow Julian C. , Hanesiak John M. , Burrows William R.
Published: September 2011

The purpose of this study was to focus on how anomalies in the normalized difference vegetation index (NDVI; a proxy for soil moisture) over the Canadian Prairies can condition the convective boundary layer (CBL) so as to inhibit or facilitate thunderstorm activity while also considering the role of synoptic-scale forcing. This study focused on a census agricultural region (CAR) over central Alberta for which we had observed lightning data (proxy for thunderstorms), remotely sensed NDVI data, and in situ rawinsonde data (to quantify impacts of vegetation vigor on the CBL characteristics) for 11 summers from 1999 to 2009. The authors’ data suggest that the occurrence of lightning over the study area is more likely (and is of longer duration) when storms develop in an environment in which the surface and upper-air synoptic-scale forcing are synchronized. On days when surface forcing and midtropospheric ascent are present, storms are more likely to be triggered when NDVI is much above average, compared to when NDVI is much below average. Additionally, the authors found the response of thunderstorm duration to NDVI anomalies to be asymmetric. That is, the response of lightning duration to anomalies in NDVI is marked when NDVI is below average but is not necessarily discernible when NDVI is above average. The authors propose a conceptual model, based largely on observations, that integrates all of the above findings to describe how a reduction in vegetation vigor—in response to soil moisture deficits—modulates the partitioning of available energy into sensible and latent heat fluxes at the surface, thereby modulating lifting condensation level heights, which in turn affect lightning activity.
Assessment of Traditional and New Eigenfunction Bases Applied to Extrapolation of Surface Geostrophic Current Time Series to Below the Surface in an Idealized Primitive Equation Simulation
Authors: Scott Robert B. , Furnival Darran G.
Published: September 2011

Three strategies were compared for extrapolating surface geostrophic velocities to below the surface: S1, using only the barotropic or first baroclinic mode; S2, using a fixed or “phase locked” linear combination of the first baroclinic mode and the barotropic mode; and S3, a strategy similar to S2 but using a new set of basis functions. For S2 and S3, the phase locking allows one to impose zero velocity at the seafloor. The new basis functions start from zero at the surface, are not degenerate with respect to the free-surface boundary condition, and represent the adjustment of the pressure at a given depth from density surfaces responding to sea surface height undulations. In idealized primitive equation simulations, strategy S3 had the least error and allowed extrapolation to deeper levels, suggesting the new basis functions performed significantly better than the traditional baroclinic modes. In contrast, strategies S1 and S2 made poor predictions by 400-m depth. Large temporal fluctuations in the fraction of energy in the barotropic and first baroclinic modes could explain the poor predictions by strategies S1 and S2. This brings into question the interpretation of the sea surface height gradients measured by satellite altimetry in terms of first baroclinic mode motions.
Abrupt Transition to Strong Superrotation Driven by Equatorial Wave Resonance in an Idealized GCM
Authors: Arnold Nathan P. , Tziperman Eli , Farrell Brian
Published: September 2011

Persistent superrotation is seen in the atmospheres of other terrestrial bodies (Venus, Titan) but not in that of present Earth, which is distinguished by equatorial easterlies. Nevertheless, superrotation has appeared in numerical simulations of Earth’s atmosphere, from two-layer models to multilevel comprehensive GCMs. Simulations of warm climates that generate enhanced tropical convective variability seem particularly prone to superrotation, which has led to hypotheses that the warmer atmospheres of the early Pliocene and Eocene may have been superrotating, and that the phenomenon may be relevant to future climate projections.

This paper considers a positive feedback leading to superrotation based on an equatorial wave resonance that occurs in a westerly background flow. The authors present simulations with an idealized multilevel GCM forced with a zonally varying equatorial heating, which show abrupt transitions to strongly superrotating states. Linear shallow water theory is used to show that these transitions occur as the superrotating jet velocity approaches the phase speed of free equatorial Rossby wave modes, leading to a resonant amplification of the response to eddy heating and its associated equatorward momentum flux. The resonance and transition are most prominent in simulations where the meridional temperature gradient has been reduced, and hysteresis behavior is seen when the gradient is eliminated completely. No evidence is found in these simulations for the midlatitude wave feedback believed to drive abrupt transitions in two-layer models, and there is only a minor role for the axisymmetric feedback based on vertical advection by the Hadley circulation.
The Predictability of Stratospheric Warming Events: More from the Troposphere or the Stratosphere?
Authors: Sun Lantao , Robinson Walter A. , Chen Gang
Published: September 2011

The roles of the stratosphere and the troposphere in determining the predictability of stratospheric final warming and sudden warming events are evaluated in an idealized atmospheric model. For each stratospheric warming event simulated in the model, a number of forecast experiments are performed from 10 or 20 days prior to the warming onset with perturbations in the troposphere and in the stratosphere separately. It is found that the stratosphere affects predictions of warming onset primarily by providing the initial state of the zonal winds, while the tropospheric initial conditions have a large impact through the generation and propagation of planetary waves. These results correspond to the roles played by the initial zonal flow and the evolution of eddy forcings in a zonally symmetric model. The initial stratospheric zonal flow has some influence on stratospheric wave driving, but in most cases this does not significantly affect the timing of the warming, except when the initial condition is close to the onset date. These results highlight the role of the troposphere in determining stratospheric planetary wave driving and support the importance of tropospheric precursors to the stratospheric warming events.
East Antarctic Landfast Sea Ice Distribution and Variability, 2000–08
Authors: Fraser Alexander D. , Massom Robert A. , Michael Kelvin J. , Galton-Fenzi Benjamin K. , Lieser Jan L.
Published: September 2011

This study presents the first continuous, high spatiotemporal resolution time series of landfast sea ice extent along the East Antarctic coast for the period March 2000–December 2008. The time series was derived from consecutive 20-day cloud-free Moderate Resolution Imaging Spectroradiometer (MODIS) composite images. Fast ice extent across the East Antarctic coast shows a statistically significant (1.43% ±0.30% yr−1) increase. Regionally, there is a strong increase in the Indian Ocean sector (20°–90°E, 4.07% ±0.42% yr−1), and a nonsignificant decrease in the western Pacific Ocean sector (90°–160°E, −0.40% ±0.37% yr−1). An apparent shift from a negative to a positive extent trend is observed in the Indian Ocean sector from 2004. This shift also coincides with a greater amount of interannual variability. No such shift in apparent trend is observed in the western Pacific Ocean sector, where fast ice extent is typically higher and variability lower than the Indian Ocean sector. The limit to the maximum fast ice areal extent imposed by the location of grounded icebergs modulates the shape of the mean annual fast ice extent cycle to give a broad maximum and an abrupt, relatively transient minimum. Ten distinct fast ice regimes are identified, related to variations in bathymetry and coastal configuration. Fast ice is observed to form in bays, on the windward side of large grounded icebergs, between groups of smaller grounded icebergs, between promontories, and upwind of coastal features (e.g., glacier tongues). Analysis of the timing of fast ice maxima and minima is also presented and compared with overall sea ice maxima/minima timing.
The North Atlantic Jet Stream under Climate Change and Its Relation to the NAO and EA Patterns
Authors: Woollings Tim , Blackburn Mike
Published: September 2011

This paper describes recent variations of the North Atlantic eddy-driven jet stream and analyzes the mean response of the jet to anthropogenic forcing in climate models. Jet stream changes are analyzed both using a direct measure of the near-surface westerly wind maximum and using an EOF-based approach. This allows jet stream changes to be related to the widely used leading patterns of variability: the North Atlantic Oscillation (NAO) and East Atlantic (EA) pattern. Viewed in NAO–EA state space, isolines of jet latitude and speed resemble a distorted polar coordinate system, highlighting the dependence of the jet stream quantities on both spatial patterns. Some differences in the results of the two methods are discussed, but both approaches agree on the general characteristics of the climate models. While there is some agreement between models on a poleward shift of the jet stream in response to anthropogenic forcing, there is still considerable spread between different model projections, especially in winter. Furthermore, the model responses to forcing are often weaker than their biases when compared to a reanalysis. Diagnoses of jet stream changes can be sensitive to the methodologies used, and several aspects of this are also discussed.