bluuebunny/crossref_metadata_2025 huggingface dataset:
Power Reserve Control for Gas Turbines in Combined Cycle Applications
Authors: Müller Eric A. , Wihler Andrew
Published: November 2011

In order to be able to optimally operate a combined cycle power plant in a liberalized electricity market, knowledge of the plant’s maximum exportable power generation capacity is vital. However, the maximum power output of a power plant is affected by numerous variable factors, such as the ambient conditions at the plant site. In addition, the allowable plant operating range might be narrowed by a compulsory reserve margin, if the power plant is participating in a frequency regulation program. In this paper, a power reserve controller is derived, which facilitates the optimal operation of a combined cycle gas turbine power plant subject to a reserve margin requirement. The power reserve controller is based on a mathematical description of the power plant and uses an adaptation mechanism to predict on a real-time basis the maximum allowable plant load limit. Based on tests on a single shaft combined cycle power plant, the operation of the power reserve controller is demonstrated and its performance is assessed. The test results prove that the controller predicts the maximum power output of the plant with high accuracy and that it is able to maintain a desired reserve capacity for frequency response as specified.
A Methodology for Quantifying Seated Lumbar Curvatures
Authors: Leitkam Samuel T. , Reid Bush Tamara , Li Mingfei
Published: November 2011

To understand the role seating plays in the support of posture and spinal articulation, it is necessary to study the interface between a human and the seat. However, a method to quantify lumbar curvature in commercially available unmodified seats does not currently exist. This work sought to determine if the lumbar curvature for normal ranges of seated posture could be documented by using body landmarks located on the anterior portion of the body. The development of such a methodology will allow researchers to evaluate spinal articulation of a seated subject while in standard, commercially available seats and chairs. Anterior measurements of boney landmarks were used to quantify the relative positions of the ribcage and pelvis while simultaneous posterior measurements were made of lumbar curvature. The relationship between the anterior and the posterior measures was compared. The predictive capacity of this approach was evaluated by determining linear and second-order regressions for each of the four postures across all subjects and conducting a leave-one-out cross validation. The relationships between the anterior and posterior measures were approximated by linear and second-order polynomial regressions (r2 = 0.829, 0.935 respectively) across all postures. The quantitative analysis showed that openness had a significant relationship with lumbar curvature, and a first-order regression was superior to a second-order regression. Average standard errors in the prediction were 5.9° for the maximum kyphotic posture, 9.9° for the comfortable posture, 12.8° for the straight and tall, and 22.2° for the maximum lordotic posture. These results show predictions of lumbar curvature are possible in seated postures by using a motion capture system and anterior measures. This method of lumbar curvature prediction shows potential for use in the assessment of seated spinal curvatures and the corresponding design of seating to accommodate those curvatures; however, additional inputs will be necessary to better predict the postures as lordosis is increased.
Comparative Assessment of Bone Pose Estimation Using Point Cluster Technique and OpenSim
Authors: Lathrop Rebecca L. , Chaudhari Ajit M. W. , Siston Robert A.
Published: November 2011

Estimating the position of the bones from optical motion capture data is a challenge associated with human movement analysis. Bone pose estimation techniques such as the Point Cluster Technique (PCT) and simulations of movement through software packages such as OpenSim are used to minimize soft tissue artifact and estimate skeletal position; however, using different methods for analysis may produce differing kinematic results which could lead to differences in clinical interpretation such as a misclassification of normal or pathological gait. This study evaluated the differences present in knee joint kinematics as a result of calculating joint angles using various techniques. We calculated knee joint kinematics from experimental gait data using the standard PCT, the least squares approach in OpenSim applied to experimental marker data, and the least squares approach in OpenSim applied to the results of the PCT algorithm. Maximum and resultant RMS differences in knee angles were calculated between all techniques. We observed differences in flexion/extension, varus/valgus, and internal/external rotation angles between all approaches. The largest differences were between the PCT results and all results calculated using OpenSim. The RMS differences averaged nearly 5° for flexion/extension angles with maximum differences exceeding 15°. Average RMS differences were relatively small (< 1.08°) between results calculated within OpenSim, suggesting that the choice of marker weighting is not critical to the results of the least squares inverse kinematics calculations. The largest difference between techniques appeared to be a constant offset between the PCT and all OpenSim results, which may be due to differences in the definition of anatomical reference frames, scaling of musculoskeletal models, and/or placement of virtual markers within OpenSim. Different methods for data analysis can produce largely different kinematic results, which could lead to the misclassification of normal or pathological gait. Improved techniques to allow non-uniform scaling of generic models to more accurately reflect subject-specific bone geometries and anatomical reference frames may reduce differences between bone pose estimation techniques and allow for comparison across gait analysis platforms.
Simulating Distal Radius Fracture Strength Using Biomechanical Tests: A Modeling Study Examining the Influence of Boundary Conditions
Authors: Edwards W. Brent , Troy Karen L.
Published: November 2011

Distal radius fracture strength has been quantified using in vitro biomechanical testing. These tests are frequently performed using one of two methods: (1) load is applied directly to the embedded isolated radius or (2) load is applied through the hand with the wrist joint intact. Fracture loads established using the isolated radius method are consistently 1.5 to 3 times greater than those for the intact wrist method. To address this discrepancy, a validated finite element modeling procedure was used to predict distal radius fracture strength for 22 female forearms under boundary conditions simulating the isolated radius and intact wrist method. Predicted fracture strength was highly correlated between methods (r = 0.94; p < 0.001); however, intact wrist simulations were characterized by significantly reduced cortical shell load carriage and increased stress and strain concentrations. These changes resulted in fracture strength values less than half those predicted for the isolated radius simulations (2274 ± 824 N for isolated radius, 1124 ± 375 N for intact wrist; p < 0.001). The isolated radius method underestimated the mechanical importance of the trabecular compartment compared to the more physiologically relevant intact wrist scenario. These differences should be borne in mind when interpreting the physiologic importance of mechanical testing and simulation results.
Experimental Evolution of Reduced Sex Ratio Adjustment Under Local Mate Competition
Authors: Macke Emilie , Magalhães Sara , Bach Fabien , Olivieri Isabelle
Published: November 2011

Tests of Hamilton’s theory on a spider mite show that populations evolve with less phenotypic plasticity in their sex ratio.
Application of rock cover alteration ratio concept in preliminary design of unlined pressure tunnels
Authors: Rancourt André J. , Mitri Hani
Published: November 2011

Unlined pressure tunnels were first driven by the Norwegians into hard granitic rock, which is the ideal material for this type of structure. However, the increase in demand for electric power has propelled the industry to develop projects at sites all over the world with less favourable geological conditions. The paper places emphasis on the preliminary design phase when no field measurements are available. A recent study by Rancourt (published in 2010) has investigated the spatial distribution of the minimum stress that is required to control hydraulic jacking around unlined pressure tunnels. Various surface topographic profiles including slopes, hills, and valleys; the rock cover to tunnel diameter ratio; as well as the presence of geological features such as shear zones and dykes were investigated with numerical modelling. Effective rock cover predictions are compared to those given by the well-known Norwegian design criterion, and a correction factor called cover alteration ratio (CAR) has been introduced. In this paper, a design methodology is proposed for use of CAR at the preliminary design stage in the form of a factor of safety against hydraulic jacking to be used in conjunction with the Norwegian criterion. Limitations on the use of the Norwegian criterion are highlighted.
Progressive failures in eastern Canadian and Scandinavian sensitive clays
Authors: Locat Ariane , Leroueil Serge , Bernander Stig , Demers Denis , Jostad Hans Petter , Ouehb Lyes
Published: November 2011

Observations from past events are used to show that the concept of progressive failure may explain translational progressive landslides and spreads — large landslides occurring in sensitive clays. During progressive failure, the strain-softening behaviour of the soil causes unstable forces to propagate a failure surface further in the slope. Translational progressive landslides generally take place in long, gently inclined slopes. Instability in a steeper upslope area is followed by redistribution of stress, which increases earth pressure further downslope. Passive failure may therefore occur in less-inclined ground, heaving the soil. Spreads are usually trigged by erosion of a deposit having a higher angle near the toe. Instability starts near the toe of the slope and propagates into the deposit, reducing earth pressure. This may lead to the formation of an active failure with dislocation of the deposit into horsts and grabens. The failure mechanism of both types of landslides is controlled by the stresses in the slope and the stress–strain behaviour of the soil. The mechanism presented explains the sensitivity of a slope to minor disturbances and the resulting high retrogressions observed for such landslides in Scandinavia and eastern Canada.
A laboratory investigation of the dynamic properties of tailings
Authors: James Michael , Aubertin Michel , Wijewickreme Dharma , Wilson G. Ward
Published: November 2011

The dynamic response of tailings from a gold mine located in western Quebec was evaluated using cyclic laboratory testing. These tailings are classified as nonplastic silt and sand. Specimens of the tailings were prepared as slurries, consolidated to vertical effective stresses of 100–400 kPa, and subjected to cyclic direct simple shear testing with cyclic stress ratio, CSR, values between 0.075 and 0.15. The shear modulus reduction of the tailings under cyclic loading was found to be fairly similar to that described for clean sands in the literature. The cyclic resistance ratio, CRR (which reflects the liquefaction resistance), of the samples was not significantly affected by the effective consolidation stress (in the range considered here). Analysis of test results with the simplified method of liquefaction evaluation indicates that this method may be applicable to these tailings. However, other factors, such as the possible effects of layering and ageing of the tailings in situ, should also be considered in such an assessment.
Inter-ramp and bench design of open-pit mines: the Portage pit case study
Authors: Grenon Martin , Laflamme Amélie-Julie
Published: November 2011

Using a case study, this paper presents an integrated methodology for assessing structural slope stability at the inter-ramp and bench levels. Robust algorithms have been developed and implemented to compute, at inter-ramp and bench levels, slope orientations and slope stability using input data compatible with a commercially available mine-design software tool database structure. Multi-criteria stability analyses were performed based on various design criteria. Susceptibility maps were produced enabling the identification of zones of concern in the designed pit. The obtained results suggest that inter-ramp angles do not present instability concerns over the entire pit surface. At bench levels, potential instability zones were identified within two structural domains totalling 6% of the total pit surface.
Limit equilibrium analysis for the design of backfilled stope barricades made of waste rock
Authors: Li Li , Aubertin Michel
Published: November 2011

Backfilling of underground stopes is commonly applied in mining operations. Barricades are required to hold the fill material in the stope during and after placement. As such barricades may be constructed with waste rock, there is a need to develop solutions to analyse their response. This paper presents a limit equilibrium analysis solution for defining the dimensions of waste rock barricades. The proposed solution applies to drained (without pore-water pressure) and submerged (with pore-water pressure) conditions. The solutions are presented and applied to sample cases.
Optimization of perforation drilling for mitigating punch-through in multi-layered clays
Authors: Hossain M.S. , Cassidy M.J. , Baker R. , Randolph M.F.
Published: November 2011

“Spudcan” foundations for mobile drilling rigs continue to exhibit a high failure rate in the offshore oil and gas industry. The more frequent use of larger jack-ups in highly stratified regions, such as the Sunda Shelf in Southeast Asia, contributes to this concerning increase in “punch-through” incidents, which can lead to buckling of a leg or even toppling of the rig. An industry practice known as “perforation drilling” is sometimes used to mitigate the punch-through risk in layered clays, extracting soil from the upper strong layer before the jack-up is installed. This paper reports results from centrifuge model tests exploring the efficiency of perforation drilling. The soil conditions tested simulate offshore strength profiles that have reported punch-through failures. An experimental method for “drilling” sites in an enhanced gravity centrifuge environment was developed and the installation responses of model spudcan foundations penetrating through multi-layered clays with interbedded stiff layers were recorded. The experimental results show that the removal of soil inside the spudcan perimeter, with an area of 9% perforated, eliminated rapid leg run and severe punch-through on the two- and four-layer seabed profiles tested. This confirms the effectiveness of perforation drilling and indicates how the offshore drilling plan may be optimized.
Effect of immobilizations on the activity and space use of female moose (Alces alces)
Authors: Neumann Wiebke , Ericsson Göran , Dettki Holger , Arnemo Jon M.
Published: November 2011

Studies of free-ranging wildlife often involve animal capture and fitting of tracking devices. Capturing wildlife may result in behavioral alterations. Thus, there is a need to evaluate the effects of capture on study animals to identify potential biases influencing the research. We assessed the short-term response of 15 GPS/GSM-collared adult female moose ( Alces alces (L., 1758)) and immobilization and handling by comparing moose rates of movement and net square displacement before and after recapture. Moose were more active up to 7 h and increased their spatial displacement for 4.5 days after recapture compared with movement patterns before recapture. Opposite to our predictions, moose did not reduced their movement rates after their initial displacement following capture and recovery, i.e., moose did not show any indication for a residual effect. We recommend using individuals as their own controls in analyses of capture impacts to account adequately for individual behavioral differences. We recommend omitting data of at least the first 5 days following capture for analyses of moose movement and distribution.
Testing climate-based species distribution models with recent field surveys of pond-breeding amphibians in eastern Missouri
Authors: Trumbo D.R. , Burgett A.A. , Knouft J.H.
Published: November 2011

Species distribution models (SDMs) have become an important tool for ecologists by providing the ability to predict the distributions of organisms based on species niche parameters and available habitat across broad geographic areas. However, investigation of the appropriate extent of environmental data needed to make accurate predictions has received limited attention. We investigate whether SDMs developed with regional climate and species locality data (i.e., within Missouri, USA) produce more accurate predictions of species occurrences than models developed with data from across an entire species range. To test the accuracy of the model predictions, field surveys were performed in 2007 and 2008 at 103 study ponds for eight amphibian study species. Models developed using data from across the entire species range did not accurately predict the occurrences of any study species. However, models developed using data only from Missouri produced accurate predictions for four study species, all of which are near the edge of their geographic ranges within the study area. These results suggest that species distribution modeling with regionally focused data may be preferable for local ecological and conservation purposes, and that climate factors may be more important for determining species distributions at the edge of their geographic ranges.
TOOLS FOR EXTRACTING NEW PHYSICS IN EVENTS WITH MISSING TRANSVERSE MOMENTUM
Authors: GRIPAIOS BEN
Published: November 2011

We review tools that have been developed in recent years to maximize our ability to discover and characterize new physics appearing in LHC events with missing transverse momentum.
THE EFFECTIVE MASS OF STRONG-COUPLING MAGNETOPOLARONS IN A PARABOLIC QUANTUM DOT
Authors: CHEN SHI-HUA , YAO QING-ZHOU
Published: November 2011

Within the framework of the Landau–Pekar variational method we have investigated the effective mass of strong-coupling magnetopolarons in a parabolic quantum dot. The effective mass as functions of the magnetic field strength and the confinement length of the quantum dot are obtained in the Gaussian function approximation. It is shown that the effective mass increases with the increasing magnetic field strength and increases with the decrease in the size of the quantum dot (QD).
FINDING SIMPLICES CONTAINING THE ORIGIN IN TWO AND THREE DIMENSIONS
Authors: ELBASSIONI KHALED , ELMASRY AMR , MAKINO KAZUHISA
Published: November 2011

We show that finding the simplices containing a fixed given point among those defined on a set of n points can be done in O(n + k) time for the two-dimensional case, and in O(n2 + k) time for the three-dimensional case, where k is the number of these simplices.

As a byproduct, we give an alternative (to the algorithm in Ref. 4) O(n log r) algorithm that finds the red-blue boundary for n bichromatic points on the line, where r is the size of this boundary. Another byproduct is an O(n2 + t) algorithm that finds the intersections of line segments having two red endpoints with those having two blue endpoints defined on a set of n bichromatic points in the plane, where t is the number of these intersections.
FITTING FLATS TO POINTS WITH OUTLIERS
Authors: DA FONSECA GUILHERME D.
Published: November 2011

Determining the best shape to fit a set of points is a fundamental problem in many areas of computer science. We present an algorithm to approximate the k-flat that best fits a set of n points with n - m outliers. This problem generalizes the smallest m-enclosing ball, infinite cylinder, and slab. Our algorithm gives an arbitrary constant factor approximation in O(nk+2/m) time, regardless of the dimension of the point set. While our upper bound nearly matches the lower bound, the algorithm may not be feasible for large values of k. Fortunately, for some practical sets of inliers, we reduce the running time to O(nk+2/mk+1), which is linear when m = Ω(n).
Tumor necrosis factor receptor 1 functions as a tumor suppressor
Authors: Chang Fengqi , Lacey Michelle R. , Bouljihad Mostafa , Bentrup Kerstin Höner zu , Fortgang Ilana S.
Published: November 2011

Tumor necrosis factor (TNF) is a key player in inflammatory bowel disease and has been variably associated with carcinogenesis, but details of the cross talk between inflammatory and tumorigenic pathways remain incompletely understood. It has been shown that, in C57BL/6 mice, signaling via TNF receptor 1 (TNFR1) is protective from injury and inflammation in experimental colitis. Therefore, we hypothesized that loss of TNFR1 signaling would confer increased risk of developing colitis-associated carcinoma. Using three models of murine tumorigenesis based on repeated bouts of inflammation or systemic tumor initiator, we sought to determine the roles of TNF and TNFR1 with regard to neoplastic transformation in the colon in wild-type (WT), TNFR1 knockout (R1KO), and TNF knockout (TNFKO) mice. We found R1KO animals to have more severe disease, as defined by weight loss, hematochezia, and histology. TNFKO mice demonstrated less weight loss but were consistently smaller, and rates and duration of hematochezia were comparable to WT mice. Histological inflammation scores were higher and neoplastic lesions occurred more frequently and earlier in R1KO mice. Apoptosis is not affected in R1KO mice although epithelial proliferation following injury is more ardent even before tumorigenesis is apparent. Lastly, there is earlier and more intense expression of activated β-catenin in these mice, implying a connection between TNFR1 and Wnt signaling. Taken together, these findings show that in the context of colitis-associated carcinogenesis TNFR1 functions as a tumor suppressor, exerting this effect not via apoptosis but by modulating activation of β-catenin and controlling epithelial proliferation.
Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress
Authors: Lu Yongke , Leung Tung Ming , Ward Stephen C. , Nieto Natalia
Published: November 2011

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the l-citrulline/nitric oxide (NO·) salvage pathway to continually supply l-arginine from l-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/−mice ( Ass−/−mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/−mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/−compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration.
Contribution of arterial blood pressure and PaCO2 to the cerebrovascular responses to motor stimulation
Authors: Panerai Ronney B. , Salinet Angela S. M. , Robinson Thompson G.
Published: November 2011

Motor stimulation induces a neurovascular response that can be detected by continuous measurement of cerebral blood flow (CBF). Simultaneous changes in arterial blood pressure (ABP) and PaCO2 have been reported, but their influence on the CBF response has not been quantified. Continuous bilateral recordings of CBF velocity (CBFV), ABP, and end-tidal CO2 (ETCO2) were obtained in 10 healthy middle-aged subjects at rest and during 60 s of repetitive, metronome-controlled (1 Hz) elbow flexion. A multivariate autoregressive-moving average model was adopted to quantify the relationship between beat-to-beat changes in ABP, breath-by-breath ETCO2, and the motor stimulus, represented by the metronome on-off signal (inputs), and the CBFV response to stimulation (output). All three inputs contributed to explain CBFV variance following stimulation. For the ipsi- and contralateral hemispheres, ABP explained 20.3 ± 17.3% ( P = 0.0007) and 19.5 ± 17.2% ( P = 0.01) of CBFV variance, respectively. Corresponding values for ETCO2 and metronome signals were 22.0 ± 24.2% ( P = 0.008), 24.0 ± 24.1% ( P = 0.037), 32.7 ± 22.5% ( P = 0.0015), and 43.2 ± 25.1% ( P = 0.013), respectively. Synchronized population averages suggest that the initial sudden change in CBFV was largely due to ABP, while the influence of ETCO2 was more erratic. The component due to elbow flexion showed a well-defined pattern, with rise time slower than the main CBFV change but reaching a stable plateau after 15 s of stimulation. Identifying and removing the influences of ABP and PaCO2 to motor-induced changes in CBF should lead to more robust estimates of neurovascular coupling and better understanding of its physiological covariates.
The energetic cost of maintaining lateral balance during human running
Authors: Arellano Christopher J. , Kram Rodger
Published: November 2011

To quantify the energetic cost of maintaining lateral balance during human running, we provided external lateral stabilization (LS) while running with and without arm swing and measured changes in energetic cost and step width variability (indicator of lateral balance). We hypothesized that external LS would reduce energetic cost and step width variability of running (3.0 m/s), both with and without arm swing. We further hypothesized that the reduction in energetic cost and step width variability would be greater when running without arm swing compared with running with arm swing. We controlled for step width by having subjects run along a single line (zero target step width), which eliminated any interaction effects of step width and arm swing. We implemented a repeated-measures ANOVA with two within-subjects fixed factors (external LS and arm swing) to evaluate main and interaction effects. When provided with external LS (main effect), subjects reduced net metabolic power by 2.0% ( P = 0.032) and step width variability by 12.3% ( P = 0.005). Eliminating arm swing (main effect) increased net metabolic power by 7.6% ( P < 0.001) but did not change step width variability ( P = 0.975). We did not detect a significant interaction effect between external LS and arm swing. Thus, when comparing conditions of running with or without arm swing, external LS resulted in a similar reduction in net metabolic power and step width variability. We infer that the 2% reduction in the net energetic cost of running with external LS reflects the energetic cost of maintaining lateral balance. Furthermore, while eliminating arm swing increased the energetic cost of running overall, arm swing does not appear to assist with lateral balance. Our data suggest that humans use step width adjustments as the primary mechanism to maintain lateral balance during running.
Mild heat stress induces mitochondrial biogenesis in C2C12 myotubes
Authors: Liu Chien-Ting , Brooks George A.
Published: November 2011

During endurance exercise, most (≈75%) of the energy derived from the oxidation of metabolic fuels and ATP hydrolysis of muscle contraction is liberated as heat, the accumulation of which leads to an increase in body temperature. For example, the temperature of exercising muscles can rise to 40°C. Although severe heat injury can be deleterious, several beneficial effects of mild heat stress (HS), such as the improvement of insulin sensitivity in patients with type 2 diabetes, have been reported. However, among all cellular events induced by mild HS from physical activities, the direct effects and mechanisms of mild HS on mitochondrial biogenesis in skeletal muscle are least characterized. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In C2C12 myotubes, we found that 1 h mild HS at 40°C upregulated both AMPK activity and SIRT1 expression, as well as increased the expression of several mitochondrial biogenesis regulatory genes including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and transcription factors involved in mitochondrial biogenesis. In particular, PGC-1α expression was found to be transcriptionally regulated by mild HS. Additionally, after repeated mild HS for 5 days, protein levels of PGC-1α and several mitochondrial oxidative phosphorylation subunits were also upregulated. Repeated mild HS also significantly increased mitochondrial DNA copy number. In conclusion, these data show that mild HS is sufficient to induce mitochondrial biogenesis in C2C12 myotubes. Temperature-induced mitochondrial biogenesis correlates with activation of the AMPK-SIRT1-PGC-1α pathway. Therefore, it is possible that muscle heat production during exercise plays a role in mitochondrial biogenesis.
The White Adipose Tissue Used in Lipotransfer Procedures Is a Rich Reservoir of CD34+ Progenitors Able to Promote Cancer Progression
Authors: Martin-Padura Ines , Gregato Giuliana , Marighetti Paola , Mancuso Patrizia , Calleri Angelica , Corsini Chiara , Pruneri Giancarlo , Manzotti Michela , Lohsiriwat Visnu , Rietjens Mario , Petit Jean-Yves , Bertolini Francesco
Published: November 2011

Previous studies have suggested a “catalytic role” in neoplastic angiogenesis and cancer progression for bone marrow–derived endothelial progenitor cells (EPC). However, preclinical and clinical studies have shown that the quantitative role of marrow-derived EPCs in cancer vascularization is extremely variable. We have found that human and murine white adipose tissue (WAT) is a very rich reservoir of CD45-CD34+ EPCs with endothelial differentiation potential, containing a mean of 263 times more CD45-CD34+ cells/mL than bone marrow. Compared with marrow-derived CD34+ cells mobilized in blood by granulocyte colony–stimulating factor, purified WAT-CD34+ cells expressed similar levels of stemness-related genes, significantly increased levels of angiogenesis-related genes, and increased levels of FAP-α, a crucial suppressor of antitumor immunity. In vitro, WAT-CD34+ cells generated mature endothelial cells and capillary tubes as efficiently as mature mesenchymal cells. The coinjection of human WAT-CD34+ cells from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth and metastases in several orthotopic models of human breast cancer in immunodeficient mice. Endothelial cells derived from human WAT-CD34+ cells lined the lumen of cancer vessels. These data indicate that CD34+ WAT cells can promote cancer progression and metastases. Our results highlight the importance of gaining a better understanding of the role of different WAT-derived cells used in lipotransfer for breast reconstruction in patients with breast cancer. Cancer Res; 72(1); 325–34. ©2011 AACR.
Genomic Complexity and AKT Dependence in Serous Ovarian Cancer
Authors: Hanrahan Aphrothiti J. , Schultz Nikolaus , Westfal Maggie L. , Sakr Rita A. , Giri Dilip D. , Scarperi Stefano , Janikariman Manickam , Olvera Narciso , Stevens Ellen V. , She Qing-Bai , Aghajanian Carol , King Tari A. , de Stanchina Elisa , Spriggs David R. , Heguy Adriana , Taylor Barry S. , Sander Chris , Rosen Neal , Levine Douglas A. , Solit David B.
Published: November 2011

Effective oncoprotein-targeted therapies have not yet been developed for ovarian cancer. To explore the role of phosphatidylinositol 3-kinase (PI3K)/AKT signaling in this disease, we performed a genetic and functional analysis of ovarian cancer cell lines and tumors. PI3K pathway alterations were common in both, but the spectrum of mutational changes differed. Genetic activation of the pathway was necessary, but not sufficient, to confer sensitivity to selective inhibition of AKT and cells with RAS pathway alterations or RB1 loss were resistant to AKT inhibition, whether or not they had coexistent PI3K/AKT pathway activation. Inhibition of AKT1 caused growth arrest in a subset of ovarian cell lines, but not in those with AKT3 expression, which required pan-AKT inhibition. Thus, a subset of ovarian tumors is sensitive to AKT inhibition, but the genetic heterogeneity of the disease suggests that effective treatment with AKT pathway inhibitors will require a detailed molecular analysis of each patient's tumor.

Significance: A subset of ovarian cancers exhibits AKT pathway activation and is sensitive to selective AKT inhibition. Ovarian tumors exhibit significant genetic heterogeneity and thus an individualized approach based on real-time, detailed genomic and proteomic characterization of individual tumors will be required for the successful application of PI3K/AKT pathway inhibitors in this disease. Cancer Discovery; 2(1); 56–67. ©2011 AACR.

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Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation
Authors: Leick Edna A. , Reis Fabiana G. , Honorio-Neves Flávia Alves , Almeida-Reis Rafael , Prado Carla M. , Martins Mílton A. , Tibério Iolanda F.L.C.
Published: November 2011

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1–5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling.
Expression of Toll-Like Receptors 2, 4 and 9 in Patients with Guillain-Barré Syndrome
Authors: Wang Yu-Zhong , Liang Qiu-Hua , Ramkalawan Hhoonisha , Wang Yan-Li , Yang Yan-Fang , Zhou Wen-Bin , Tian Fa-Fa , Li Jing , Yang Huan
Published: November 2011

Objective: A myriad of transcription factors and inflammatory cytokines have been described to participate in the pathogenesis of Guillain-Barré syndrome (GBS). However, the innate immunity components – Toll-like receptors (TLRs) – have never been explored in this disease. We therefore investigated the expression of TLR2, 4 and 9 in the peripheral circulation of GBS patients as well as healthy controls. Methods: Twenty-one GBS patients and 21 healthy donors participated in this study. Peripheral blood mononuclear cells were used for mRNA and protein analysis of TLR-related molecules. Also, peripheral blood mononuclear cells from different subjects were incubated with different TLR agonists and the subsequent IFN-γ secretion was determined. Results: Expression of TLR2, 4 and 9 as well as their related signaling molecules were higher in GBS patients compared to healthy controls. Disability scores of GBS patients had a strong positive correlation with the high levels of expression of TLR2, 4 and 9. Conclusions: The TLR signaling pathway may be involved in the pathogenesis of GBS.
Exploring the Relationships between Hemoglobin, the Endothelium and Vascular Health in Patients with Chronic Kidney Disease
Authors: Weber Catherine , Sigrist Mhairi , Romann Alexandra , Whalen Beth A. , Levin Adeera
Published: November 2011

Background/Aims: The ideal hemoglobin target in chronic kidney disease remains unknown. Ultimately, individualized targets may depend upon the properties of the patient’s endothelial and vascular milieu, and thus the complex relationships between these factors need to be further explored. Methods: Forty-six patients with a glomerular filtration rate (GFR) <30 ml/min/1.73 m2 or on renal replacement therapy underwent measurement of hemoglobin, endothelial microparticles (EMPs) and aortic pulse wave velocity (PWV) at 0, 3 and 6 months. In addition, a number of inflammatory, cardiac and vascular biomarkers were measured at baseline. Results: No correlation was observed between baseline values of PWV and EMPs, PWV and hemoglobin, or hemoglobin and EMPs in the overall cohort. When stratified by CKD status, a positive correlation was observed between PWV and EMP CD41–/CD144+ in patients with GFR <30 ml/min/1.73 m2 only (r = 0.54, p = 0.01). Asymmetric dimethylarginine correlated with baseline PWV (r = 0.27, p = 0.07), and remained significantly correlated with the 3- and 6-month PWV measurement. Conclusions: In this small heterogeneous cohort of dialysis and non-dialysis patients, we were unable to describe a physiologic link between anemia, endothelial dysfunction and arterial stiffness.
Nucleotide-Binding Oligomerization Domain-Like Receptors and Inflammasomes in the Pathogenesis of Non-Microbial Inflammation and Diseases
Authors: Mason D. Randal , Beck Paul L. , Muruve Daniel A.
Published: November 2011

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) or nucleotide-binding domain leucine-rich repeat-containing family of genes plays an important role in the development of innate immune responses. Some family members are known to form multiprotein complexes known as inflammasomes that regulate the processing and secretion of proinflammatory mediators, such as interleukin-1β and interleukin-18. Activity of the inflammasome is triggered not only by microbial infection, but also by a wide range of both exogenous and endogenous noninfectious stimuli. Consequently, the dysregulation of inflammasome activity is associated with numerous proinflammatory, non-microbial human diseases. The discovery of NLRP3 gene mutations in autoinflammatory diseases such as Muckle-Wells syndrome has led to the association of NLRs in the pathogenesis of many non-microbial diseases that include arthritis, neurodegenerative disorders, metabolic disorders (obesity and diabetes), cardiovascular disease (atherosclerosis, myocardial infarction), inflammatory bowel disease, kidney disease and hypersensitivity dermatitis. A number of NLRs are also associated with human disease in the absence of inflammasome activity, suggesting additional roles for NLRs in the regulation of inflammation and disease. This review serves to provide a summary of NLR-associated diseases and, where possible, the mechanisms behind the associations.
Reperfusion Injury Intensifies the Adaptive Human T Cell Alloresponse in a Human-Mouse Chimeric Artery Model
Authors: Yi Tai , Fogal Birgit , Hao Zhengrong , Tobiasova Zuzana , Wang Chen , Rao Deepak A. , Al-Lamki Rafia S. , Kirkiles-Smith Nancy C. , Kulkarni Sanjay , Bradley John R. , Bothwell Alfred L.M. , Sessa William C. , Tellides George , Pober Jordan S.
Published: November 2011

Objective—

Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials.

Methods and Results—

Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to “heal in” for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell–mediated injury to human artery segments.

Conclusion—

We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses.
Stroke Prevention in the Developing World
Authors: Feigin Valery L. , Krishnamurthi Rita
Published: November 2011

In the early 21st century, developing countries are experiencing an ever-increasing burden of stroke due its high morbidity and associated disability. Given the limited health resources available in developing countries, stroke prevention there is of paramount importance. This narrative review summarizes currently available evidence for stroke prevention in the developing world and outlines their major strategies and priorities.
Neuroprotective Effect of Acute Ethanol Administration in a Rat With Transient Cerebral Ischemia
Authors: Wang Fei , Wang Yu , Geng Xiaokun , Asmaro Karam , Peng Changya , Sullivan Jonathon M. , Ding Jamie Y. , Ji Xunming , Ding Yuchuan
Published: November 2011

Background and Purpose—

Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke.

Methods—

Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Five sets of experiments were conducted: to determine the dose–response effect of ethanol on brain infarction and functional outcome; to determine whether combining ethanol and hypothermia produces synergistic neuroprotection; to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage in a hemorrhagic or ischemic stroke or after administration of thrombolytics; and to test the affect of ethanol on hypoxia-inducible factor-1α protein expression.

Results—

Ethanol at 1.5 g/kg reduced infarct volume and behavioral dysfunction when administered at 2, 3, or 4 hours after middle cerebral artery occlusion. The protective effect of ethanol was not improved when paired with hypothermia. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue-type plasminogen activator or urokinase. Ethanol treatment (1.5 g/kg) increased protein levels of hypoxia-inducible factor-1α at 3 hours postreperfusion.

Conclusions—

Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, increases expression of hypoxia-inducible factor-1α, and does not promote intracerebral hemorrhage when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke.
A Rat Model of Studying Tissue-Type Plasminogen Activator Thrombolysis in Ischemic Stroke With Diabetes
Authors: Fan Xiang , Qiu Jianhua , Yu Zhanyang , Dai Haibin , Singhal Aneesh B. , Lo Eng H. , Wang Xiaoying
Published: November 2011

Background and Purpose—

Poststroke hyperglycemia and diabetes mellitus are associated with lower thrombolytic efficacy and an increased risk of postischemic cerebral hemorrhage. We aimed to develop a rodent model of thrombolysis in diabetic stroke that mimics the clinical situation.

Method—

Male 6-week Type I diabetic rats (14 weeks old) were subjected to embolic focal stroke and treated with tissue-type plasminogen activator at 1.5 hours. Reperfusion and 24-hour neurological outcomes were measured and compared with nondiabetic control rats.

Results—

Diabetic rats exhibited resistance to thrombolytic reperfusion, larger infarction volumes, and increased intracerebral hemorrhage.

Conclusions—

This animal model would be relevant to future studies investigating pathophysiological mechanisms and in developing new therapeutic approaches to enhance the efficacy of tissue-type plasminogen activator thrombolysis in stroke patients with diabetes or poststroke hyperglycemia.
Alliances and Trade with Sanctioned States
Authors: Early Bryan R.
Published: November 2011

What determines how US economic sanctions affect the international trade conducted with their targets? This article develops a liberal-based explanation for why economic sanctions increase their targets’ trade with some third parties and decrease it with others. It is theorized that the effects of defense pact alliances between sender and third-party states are conditional upon the strength of the third parties’ commercial dependence upon the target states. Third parties will cooperate with senders when the costs are low, but use their alliance relationships as cover to sanctions bust when the commercial benefits are high. This suggests that the United States can best gain the support of allies whose cooperation matters the least, while the allies whose support is most important tend to sanctions bust. It is also theorized that a target state’s allies trade more with it than its nonallies. An empirical analysis of ninety-six episodes of US-imposed sanctions supports these hypotheses.