bluuebunny/crossref_metadata_2025 huggingface dataset:
CAVITATION STRENGTH OF LIQUIDS WITH LARGE MOLECULES
Authors: VINOGRADOV VLADIMIR E. , PAVLOV PAVEL A.
Published: August 2013

The cavitation strength of liquids has been studied at atmospheric pressure by applying tensile stress pulses of duration up to 3 μs and amplitude up to 20 MPa within the temperature range from room temperature to the temperature of explosive boiling-up of the liquid. At high temperatures, where in absolute value the tensile strength does not exceed 1–2 times the critical pressure, agreement between classical nucleation theory and experiment is observed within the experimental error. With a decrease of the temperature the tensile strength of the liquid increases, but the experimental values of the breaking strength are lower than those predicted from theory. The dependence of the degree of discrepancy between theory and experiment on the number of atoms in the molecules of the liquids investigated is shown.
INCONSISTENCIES FROM A RUNNING COSMOLOGICAL CONSTANT
Authors: HAMBER HERBERT W. , TORIUMI REIKO
Published: August 2013

We examine the general issue of whether a scale dependent cosmological constant can be consistent with general covariance, a problem that arises naturally in the treatment of quantum gravitation, where coupling constants generally run as a consequence of renormalization group effects. The issue is approached from several points of view, which include the manifestly covariant functional integral formulation, covariant continuum perturbation theory about two dimensions, the lattice formulation of gravity, and the nonlocal effective action and effective field equation methods. In all cases we find that the cosmological constant cannot run with scale, unless general covariance is explicitly broken by the regularization procedure. Our results are expected to have some bearing on current quantum gravity calculations, but more generally should apply to phenomenological approaches to the cosmological vacuum energy problem.
PSEUDODYNAMIC TECHNIQUE TO OBTAIN RELIABLE SHOCK RESPONSE
Authors: CHANG SHUENN-YIH , CHEN TING-WEI , YANG CHING-HAO
Published: August 2013

The use of a pseudodynamic testing method to obtain a response from an impulsive loading may lead to an incorrect test result even though the test setup is properly adjusted and the time step is appropriately chosen based on general considerations. The cause to this problem is analytically explored and a pseudodynamic technique is proposed to overcome this difficulty. The technique is to perform a single small time step immediately upon termination of the applied impulse, while the other time steps can still be conducted by the time step determined from general considerations. The feasibility of this technique is analytically verified and confirmed by a series of pseudodynamic tests for both linear elastic systems and inelastic systems.
A SELF-DUAL FILTERING TOGGLE OPERATOR FOR SPECKLE NOISE FILTERING
Authors: DORINI LEYZA BALDO , LEITE NEUCIMAR JERÔNIMO
Published: August 2013

In this work, we formalize an alternative way to build self-dual morphological filters that extends some results obtained for morphological centers to a different class of toggle operators. Thus, a wider range of primitives can be considered without causing oscillations, a common problem in toggle mappings. We also show that the combination of the morphological filters generated by using the proposed approach with the well-known anisotropic diffusion technique yields sound results where homogeneous regions are smoothed without degrading edge information. We explore the filtering of speckle noise, an interference pattern that causes a granular aspect in the image, thus limiting its interpretation and making it difficult further image processing tasks. Experimental tests on both synthetic and real-world images show promising results when compared to some well-known methods related to this type of filtering.
HYBRID-TREFFTZ DISPLACEMENT FINITE ELEMENTS FOR ELASTIC UNSATURATED SOILS
Authors: MOLDOVAN IONUŢ DRAGOŞ , CAO TOAN DUC , DE FREITAS JOÃO ANTÓNIO TEIXEIRA
Published: August 2013

The displacement model of the hybrid-Trefftz finite element is formulated for elastodynamic problems defined on unsaturated soils. The mathematical formulation is based on the theory of mixtures with interfaces. The model considers the full coupling between the solid, fluid and gas phases, including the effects of relative (seepage) accelerations. The hyperbolic problem is integrated in time using a step-by-step implicit scheme that transforms it into a series of elliptic problems in space. The free-field solutions of these problems are derived in cylindrical coordinates and used to construct the domain approximation of the hybrid-Trefftz displacement element. This builds relevant physical information in the approximation basis, increasing the convergence of the elements under p-refinement and their robustness to wide variations of the frequency of the propagating wave.
Linear-time decoding of regular expander codes
Authors: Viderman Michael
Published: August 2013

Sipser and Spielman (IEEE IT, [1996]) showed that any
c
,
d
)-regular expander code with expansion parameter >¾ is decodable in linear time from a constant fraction of errors. Feldman et al. (IEEE IT, [2007]) proved that expansion parameter >⅔ + 1/3c is sufficient to correct a constant fraction of errors in polynomial time using LP decoding.

In this work, we give a simple combinatorial algorithm that achieves even better parameters. In particular, our algorithm runs in linear time and works for any expansion parameter >⅔ − 1/6c. We also prove that our decoding algorithm can be executed in logarithmic time on a linear number of parallel processors.
Can peer instruction be effective in upper-division computer science courses?
Authors: Lee Cynthia Bailey , Garcia Saturnino , Porter Leo
Published: August 2013

Peer Instruction (PI) is an active learning pedagogical technique. PI lectures present students with a series of multiple-choice questions, which they respond to both individually and in groups. PI has been widely successful in the physical sciences and, recently, has been successfully adopted by computer science instructors in lower-division, introductory courses. In this work, we challenge readers to consider PI for their upper-division courses as well. We present a PI curriculum for two upper-division computer science courses: Computer Architecture and Theory of Computation. These courses exemplify several perceived challenges to the adoption of PI in upper-division courses, including: exploration of abstract ideas, development of high-level judgment of engineering design trade-offs, and exercising advanced mathematical sophistication. This work includes selected course materials illustrating how these challenges are overcome, learning gains results comparing these upper-division courses with previous lower-division results in the literature, student attitudinal survey results (N = 501), and pragmatic advice to prospective developers and adopters. We present three main findings. First, we find that these upper-division courses achieved student learning gains equivalent to those reported in successful lower-division computing courses. Second, we find that student feedback for each class was overwhelmingly positive, with 88% of students recommending PI for use in other computer science classes. Third, we find that instructors adopting the materials introduced here were able to replicate the outcomes of the instructors who developed the materials in terms of student learning gains and student feedback.
Using POGIL to help students learn to program
Authors: Hu Helen H. , Shepherd Tricia D.
Published: August 2013

POGIL has been successfully implemented in a scientific computing course to teach science students how to program in Python. Following POGIL guidelines, the authors have developed guided inquiry activities that lead student teams to discover and understand programming concepts. With each iteration of the scientific computing course, the authors have refined the activities and learned how to better adapt POGIL for the computer science classroom. This article details how POGIL activities differ from both traditional computer science labs and other active-learning pedagogies. Background is provided on POGIL's effectiveness. The article then includes a full description of how POGIL activities were used in the scientific computing course, as well as an example POGIL activity on recursion. Discussion is provided on how to facilitate and develop POGIL activities. Quotes from student evaluations and an assessment on how well students learned to program are provided.
Talking about code
Authors: Hundhausen Christopher D. , Agrawal Anukrati , Agarwal Pawan
Published: August 2013

Given the increasing importance of soft skills in the computing profession, there is good reason to provide students with more opportunities to learn and practice those skills in undergraduate computing courses. Toward that end, we have developed an active learning approach for computing education called the
Pedagogical Code Review
(PCR). Inspired by the
code inspection
process used in the software industry, a PCR is a collaborative activity in which a small team of students, led by a trained moderator: (a) walk through segments of each other's programming solutions, (b) check the code against a list of best coding practices, and (c) discuss and log issues that arise. To evaluate the viability and effectiveness of this approach, we conducted a series of four mixed-method empirical studies of various implementations of PCRs in CS1 courses at Washington State University. The first study validated the viability of the PCR activity. Using a quasi-experimental design, the final three studies evaluated two alternative implementations of PCRs—
face-to-face
and
online
. Our results provide evidence that PCRs can promote positive attitudinal shifts, and hone skills in critical review, teamwork, and communication. Based on our findings, we present a set of best practices for implementing PCRs.
Syntax-Based Post-Ordering for Efficient Japanese-to-English Translation
Authors: Sudoh Katsuhito , Wu Xianchao , Duh Kevin , Tsukada Hajime , Nagata Masaaki
Published: August 2013

This article proposes a novel reordering method for efficient two-step Japanese-to-English statistical machine translation (SMT) that isolates reordering from SMT and solves it after lexical translation. This reordering problem, called
post-ordering
, is solved as an SMT problem from Head-Final English (HFE) to English. HFE is syntax-based reordered English that is very successfully used for reordering with English-to-Japanese SMT. The proposed method incorporates its advantage into the reverse direction, Japanese-to-English, and solves the post-ordering problem by accurate syntax-based SMT with target language syntax. Two-step SMT with the proposed post-ordering empirically reduces the decoding time of the accurate but slow syntax-based SMT by its good approximation using intermediate HFE. The proposed method improves the decoding speed of syntax-based SMT decoding by about six times with comparable translation accuracy in Japanese-to-English patent translation experiments.
Robust image annotation via simultaneous feature and sample outlier pursuit
Authors: Dong Jian , Cheng Bin , Chen Xiangyu , Chua Tat-Seng , Yan Shuicheng , Zhou Xi
Published: August 2013

Graph-based semi-supervised image annotation has achieved great success in a variety of studies, yet it essentially and intuitively suffers from both the irrelevant/noisy features (referred to as feature outliers) and the unusual/corrupted samples (referred to as sample outliers). In this work, we investigate how to derive robust sample affinity matrix via simultaneous feature and sample outlier pursuit. This task is formulated as a Dual-outlier and Prior-driven Low-Rank Representation (DP-LRR) problem, which possesses convexity in objective function. In DP-LRR, the clean data are assumed to be self-reconstructible with low-rank coefficient matrix as in LRR; while the error matrix is decomposed as the sum of a row-wise sparse matrix and a column-wise sparse matrix, the ℓ
2,1
-norm minimization of which encourages the pursuit of feature and sample outliers respectively. The DP-LRR is further regularized by the priors from side information, that is, the inhomogeneous data pairs. An efficient iterative procedure based on linearized alternating direction method is presented to solve the DP-LRR problem, with closed-form solutions within each iteration. The derived low-rank reconstruction coefficient matrix is then fed into any graph based semi-supervised label propagation algorithm for image annotation, and as a by-product, the cleaned data from DP-LRR can also be utilized as a better image representation to generally boost image annotation performance. Extensive experiments on MIRFlickr, Corel30K, NUS-WIDE-LITE and NUS-WIDE databases well demonstrate the effectiveness of the proposed formulation for robust image annotation.
A framework for network aware caching for video on demand systems
Authors: Carbunar Bogdan , Potharaju Rahul , Pearce Michael , Vasudevan Venugopal , Needham Michael
Published: August 2013

Video on Demand (VoD) services allow users to select and locally consume remotely stored content. We investigate the use of caching to solve the scalability issues of several existing VoD providers. We propose metrics and goals that define the requirements of a caching framework for CDNs of VoD systems. Using data logs collected from Motorola equipment from Comcast VoD deployments we show that several classic caching solutions do not satisfy the proposed goals. We address this issue by developing novel techniques for predicting future values of several metrics of interest. We rely on computed predictions to define the
penalty
imposed on the system, both network and caching sites, when not storing individual items. We use item penalties to devise novel caching and static content placement strategies. We use the previously mentioned data logs to validate our solutions and show that they satisfy all the defined goals.
Effect of theCopaifera langsdorffiiDesf. Leaf Extract on the Ethylene Glycol-Induced Nephrolithiasis in Rats
Authors: Oliveira Rejane Barbosa de , Coelho Eduardo Barbosa , Rodrigues Marina Rezende , Costa-Machado Ana Rita de Mello , Sousa João Paulo Barreto de , Berretta Andresa A. , Bastos Jairo Kenupp
Published: August 2013

The potential of theCopaifera langsdorffiileaves extract to prevent stone formation was analyzed by means of an ethylene glycol (EG) animal model of nephrolithiasis and anin vitrocrystallization assay. Different doses of theC. langsdorffiileaves extract were administered to rats treated with EG. Urine biochemical parameters were quantified. CaOx deposits count and analysis of osteopontin expression were conducted on kidneys fixed in formalin. Thein vitroassay was performed by turbidimetry. Phytochemical analyses of the extract were accomplished by HPLC-UV-DAD, and several compounds were isolated.C. langsdorffiileaf extract was able to avoid stone formation. The number of deposits was50.30±31.29at the higher extract dose, compared to the value of179.5±45.96achieved with the EG control. Significantly lower oxalate levels and OPN expression and increased citrate levels were observed after extract administration. In thein vitroassay, the extract diluted the formed crystals. Phytochemical analyses showed that the extract is rich in phenolic compounds that are capable of preventing stone formation. Thus, on the basis of our results, we suggest that theC. langsdorffiileaf extract has potential application in the prevention of kidney stone formation.
Optimal Control of Agricultural Insects with a Stage-Structured Model
Authors: Kang Baolin , He Mingfeng , Liu Bing
Published: August 2013

A stage-structured pest control model with impulse effects by state feedback control is formulated, and a semicontinuous dynamic system and its successor functions are defined. The sufficient conditions of existence and attractiveness of order one periodic solution are obtained by the method of successor functions. The superiority of the state feedback control strategy in this paper is that we only need to monitor the sum of immature and mature pest populations. Moreover, our results show that our method used in this paper is more efficient and easier than the existing methods.
Computational Representation of White Matter Fiber Orientations
Authors: Ferreira da Silva Adelino R.
Published: August 2013

We present a new methodology based on directional data clustering to represent white matter fiber orientations in magnetic resonance analyses for high angular resolution diffusion imaging. A probabilistic methodology is proposed for estimating intravoxel principal fiber directions, based on clustering directional data arising from orientation distribution function (ODF) profiles. ODF reconstructions are used to estimate intravoxel fiber directions using mixtures of von Mises-Fisher distributions. The method focuses on clustering data on the unit sphere, where complexity arises from representing ODF profiles as directional data. The proposed method is validated on synthetic simulations, as well as on a real data experiment. Based on experiments, we show that by clustering profile data using mixtures of von Mises-Fisher distributions it is possible to estimate multiple fiber configurations in a more robust manner than currently used approaches, without recourse to regularization or sharpening procedures. The method holds promise to support robust tractographic methodologies and to build realistic models of white matter tracts in the human brain.
New Exact Solutions for a Generalized Double Sinh-Gordon Equation
Authors: Magalakwe Gabriel , Khalique Chaudry Masood
Published: August 2013

We study a generalized double sinh-Gordon equation, which has applications in various fields, such as fluid dynamics, integrable quantum field theory, and kink dynamics. We employ the Exp-function method to obtain new exact solutions for this generalized double sinh-Gordon equation. This method is important as it gives us new solutions of the generalized double sinh-Gordon equation.
Joint Implementation of Signal Control and Congestion Pricing in Transportation Network
Authors: Mao Wei , Qin Feifei , Hu Yihong , Tan Zhijia
Published: August 2013

The policy of jointly implementing signal control and congestion pricing in the transportation network is investigated. Bilevel programs are developed to model the simultaneous optimization of signal setting and congestion toll. The upper level aims to maximize the network reserve capacity or minimize the total travel time, subject to signal setting and toll constraints. The lower level is a deterministic user equilibrium problem given a plan of signal setting and congestion charge. Then the bilevel programs are transferred into the equivalent single level programs, and the solution methods are discussed. Finally, a numerical example is presented to illustrate the concepts and methods, and it is shown that the joint implementation policy can achieve promising results.
On PID Controller Design by Combining Pole Placement Technique with Symmetrical Optimum Criterion
Authors: Nicolau Viorel
Published: August 2013

In this paper, aspects of analytical design of PID controllers are studied, by combining pole placement technique with symmetrical optimum criterion. The proposed method is based on low-order plant model with pure integrator, and it can be used for both fast and slow processes. Starting from the desired closed-loop transfer function, which contains a second-order oscillating system and a lead-lag compensator, it is shown that the zero value depends on the real-pole value of closed-loop transfer function. In addition, there is only one pole value, which satisfies the assumptions of symmetrical optimum criterion imposed to open-loop transfer function. In these conditions, by combining the pole placement technique with symmetrical optimum criterion, the analytical expressions of the controller parameters can be simplified. For simulations, PID autopilot design for heading control problem of a conventional ship is considered.
New Types of Nonlinear Waves and Bifurcation Phenomena in Schamel-Korteweg-de Vries Equation
Authors: Wu Yun , Liu Zhengrong
Published: August 2013

We study the nonlinear waves described by Schamel-Korteweg-de Vries equationut+au1/2+buux+δuxxx=0. Two new types of nonlinear waves called compacton-like waves and kink-like waves are displayed. Furthermore, two kinds of new bifurcation phenomena are revealed. The first phenomenon is that the kink waves can be bifurcated from five types of nonlinear waves which are the bell-shape solitary waves, the blow-up waves, the valley-shape solitary waves, the kink-like waves, and the compacton-like waves. The second phenomenon is that the periodic-blow-up wave can be bifurcated from the smooth periodic wave.
The Traveling Wave Solutions and Their Bifurcations for the BBM-LikeB(m,n)Equations
Authors: Li Shaoyong , Liu Zhengrong
Published: August 2013

We investigate the traveling wave solutions and their bifurcations for the BBM-likeB(m,n)equationsut+αux+β(um)x−γ(un)xxt=0by using bifurcation method and numerical simulation approach of dynamical systems. Firstly, for BBM-likeB(3,2)equation, we obtain some precise expressions of traveling wave solutions, which include periodic blow-up and periodic wave solution, peakon and periodic peakon wave solution, and solitary wave and blow-up solution. Furthermore, we reveal the relationships among these solutions theoretically. Secondly, for BBM-likeB(4,2)equation, we construct two periodic wave solutions and two blow-up solutions. In order to confirm the correctness of these solutions, we also check them by software Mathematica.
Interval-Valued Intuitionistic Hesitant Fuzzy Aggregation Operators and Their Application in Group Decision-Making
Authors: Zhang Zhiming
Published: August 2013

Hesitant fuzzy sets, permitting the membership of an element to be a set of several possible values, can be used as an efficient mathematical tool for modelling people’s hesitancy in daily life. In this paper, we extend the hesitant fuzzy set to interval-valued intuitionistic fuzzy environments and propose the concept of interval-valued intuitionistic hesitant fuzzy set, which allows the membership of an element to be a set of several possible interval-valued intuitionistic fuzzy numbers. The aim of this paper is to develop a series of aggregation operators for interval-valued intuitionistic hesitant fuzzy information. Then, some desired properties of the developed operators are studied, and the relationships among these operators are discussed. Furthermore, we apply these aggregation operators to develop an approach to multiple attribute group decision-making with interval-valued intuitionistic hesitant fuzzy information. Finally, a numerical example is provided to illustrate the application of the developed approach.
Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats
Authors: Jin Chang-Feng , Li Bo , Lin Shun-Mei , Yadav Raj-Kumar , Kim Hyung-Ryong , Chae Han-Jung
Published: August 2013

Eucommia ulmoidesOliv. (EU) has been used for treatment of liver diseases. The protective effects ofEucommia UlmoidesOliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.
A Wavelet Kernel-Based Primal Twin Support Vector Machine for Economic Development Prediction
Authors: Su Fang , Shang HaiYang
Published: August 2013

Economic development forecasting allows planners to choose the right strategies for the future. This study is to propose economic development prediction method based on the wavelet kernel-based primal twin support vector machine algorithm. As gross domestic product (GDP) is an important indicator to measure economic development, economic development prediction means GDP prediction in this study. The wavelet kernel-based primal twin support vector machine algorithm can solve two smaller sized quadratic programming problems instead of solving a large one as in the traditional support vector machine algorithm. Economic development data of Anhui province from 1992 to 2009 are used to study the prediction performance of the wavelet kernel-based primal twin support vector machine algorithm. The comparison of mean error of economic development prediction between wavelet kernel-based primal twin support vector machine and traditional support vector machine models trained by the training samples with the 3–5 dimensional input vectors, respectively, is given in this paper. The testing results show that the economic development prediction accuracy of the wavelet kernel-based primal twin support vector machine model is better than that of traditional support vector machine.
Intradiscal Pressure Changes during Manual Cervical Distraction: A Cadaveric Study
Authors: Gudavalli M. R. , Potluri T. , Carandang G. , Havey R. M. , Voronov L. I. , Cox J. M. , Rowell R. M. , Kruse R. A. , Joachim G. C. , Patwardhan A. G. , Henderson C. N. R. , Goertz C.
Published: August 2013

The objective of this study was to measure intradiscal pressure (IDP) changes in the lower cervical spine during a manual cervical distraction (MCD) procedure. Incisions were made anteriorly, and pressure transducers were inserted into each nucleus at lower cervical discs. Four skilled doctors of chiropractic (DCs) performed MCD procedure on nine specimens in prone position with contacts at C5 or at C6 vertebrae with the headpiece in different positions. IDP changes, traction forces, and manually applied posterior-to-anterior forces were analyzed using descriptive statistics. IDP decreases were observed during MCD procedure at all lower cervical levels C4-C5, C5-C6, and C6-C7. The mean IDP decreases were as high as 168.7 KPa. Mean traction forces were as high as 119.2 N. Posterior-to-anterior forces applied during manual traction were as high as 82.6 N. Intraclinician reliability for IDP decrease was high for all four DCs. While two DCs had high intraclinician reliability for applied traction force, the other two DCs demonstrated only moderate reliability. IDP decreases were greatest during moving flexion and traction. They were progressevely less pronouced with neutral traction, fixed flexion and traction, and generalized traction.
Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer
Authors: Howe Louise R. , Subbaramaiah Kotha , Hudis Clifford A. , Dannenberg Andrew J.
Published: August 2013

The increasing rate of obesity worldwide is predicted to be associated with a surge in diseases. Notably, obesity has been linked to approximately 20% of cancer cases in the United States; obesity is associated with both increased risk and worse outcomes after diagnosis. Altered levels of circulating factors are strongly implicated, including insulin, insulin-like growth factor 1, leptin, adiponectin, and interleukin-6 (IL-6). In addition, increasing attention has focused on the consequences of local adipose inflammation. Inflammatory foci characterized by crown-like structures consisting of dead adipocytes encircled by macrophages occur in white adipose depots, including the breast tissue, of most overweight and obese women. Saturated fatty acids, released as a consequence of obesity-associated lipolysis, induce macrophage activation via Toll-like receptor 4, thereby stimulating NF-κB signaling. This, in turn, activates transcription of proinflammatory genes including COX-2, IL-6, IL-1β, and TNFα. Elevated levels of proinflammatory mediators cause both local and systemic effects. Of particular relevance with regard to breast cancer is increased transcription of the CYP19 gene encoding aromatase, the rate-limiting enzyme for estrogen synthesis. Notably, this obesity–inflammation–aromatase axis provides a plausible explanation for increased rates of postmenopausal, hormone receptor–positive breast cancer associated with obesity and hence may offer targets for interventions to attenuate risk or improve prognosis. Potential approaches include weight reduction, exercise, and suppression of obesity-driven signaling pathways using pharmaceutical or dietary agents. A key future goal is to identify biomarkers that accurately report adipose inflammation, both for identification of at-risk individuals and to assess the efficacy of interventions. Clin Cancer Res; 19(22); 6074–83. ©2013 AACR.
Combining Oncolytic HSV-1 with Immunogenic Cell Death-Inducing Drug Mitoxantrone Breaks Cancer Immune Tolerance and Improves Therapeutic Efficacy
Authors: Workenhe Samuel T. , Pol Jonathan G. , Lichty Brian D. , Cummings Derek T. , Mossman Karen L.
Published: August 2013

Although antitumor activity of herpes simplex virus 1 (HSV-1) ICP0 null oncolytic vectors has been validated in murine breast cancer models, oncolytic virus treatment alone is insufficient to break immune tolerance. Thus, we investigated enhancing efficacy through combination therapy with the immunogenic cell death–inducing chemotherapeutic drug, mitoxantrone. Despite a lack of enhanced cytotoxicity in vitro, HSV-1 ICP0 null oncolytic virus KM100 with 5 μmol/L mitoxantrone provided significant survival benefit to BALB/c mice bearing Her2/neu TUBO-derived tumors. This protection was mediated by increased intratumoral infiltration of neutrophils and tumor antigen-specific CD8+ T cells. Depletion studies verified that CD8-, CD4-, and Ly6G-expressing cells are essential for enhanced efficacy of the combination therapy. Moreover, the addition of mitoxantrone to KM100 oncolytic virus treatment broke immune tolerance in BALB-neuT mice bearing TUBO-derived tumors. This study suggests that oncolytic viruses in combination with immunogenic cell death–inducing chemotherapeutics enhance the immunogenicity of the tumor-associated antigens, breaking immunologic tolerance established toward these antigens. Cancer Immunol Res; 1(5); 309–19. ©2013 AACR.
CD4+ T Effectors Specific for the Tumor Antigen NY-ESO-1 Are Highly Enriched at Ovarian Cancer Sites and Coexist with, but Are Distinct from, Tumor-Associated Treg
Authors: Ayyoub Maha , Pignon Pascale , Classe Jean-Marc , Odunsi Kunle , Valmori Danila
Published: August 2013

Whereas tumor infiltration by T effectors is generally associated with a more favorable prognosis, the accumulation of CD4+ regulatory T cells (Treg) within tumors is instead often associated with poor disease outcome. Because approaches to improve antitumor immunity aim, on one hand, at expanding tumor antigen-specific T cells and, on the other, at eliminating or inactivating Treg, an outstanding question is whether, and to what extent, tumor antigen-specific CD4+ T effectors present at tumor sites overlap with tumor-associated Treg. Here, we used MHC class II/peptide tetramers incorporating an immunodominant peptide from the human tumor-specific antigen NY-ESO-1 to assess antigen-specific CD4+ T cells among conventional CD4+ T effectors and Treg at sites of ovarian cancer. We found that, in patients who spontaneously respond to the antigen, the frequency of NY-ESO-1 tetramer+ cells detected ex vivo was highly enriched in tumors as compared with the periphery. At tumor sites, NY-ESO-1 tetramer+ cells were detected concomitantly with high proportions of Treg but were distinct from the latter and displayed characteristics of TH1 effectors. Thus, even in the presence of high proportions of Treg, tumor antigen-specific CD4+ T cells can accumulate in ovarian tumors and maintain an effector phenotype. Cancer Immunol Res; 1(5); 303–8. ©2013 AACR.
Assessing Early Growth and Adiposity: Report from an EarlyNutrition Academy Workshop
Authors: Ward Leigh C. , Poston Lucilla , Godfrey Keith M. , Koletzko Berthold ,   on behalf of the EarlyNutrition Academy
Published: August 2013

This report provides a summary of a workshop organised by the European Commission-funded EarlyNutrition Project and the EarlyNutrition Academy. Accurate and reliable methods to assess body composition are needed in research on prenatal and early post-natal influences of nutrition on later health because common surrogate measures of maternal and offspring adiposity (body fat content), such as body mass index (BMI), have relatively poor predictive power for the risk of later disease. The key goals of the workshop were to discuss approaches to assess growth and body composition from pregnancy to adolescence, to summarise conclusions and to prepare a framework for research in the EarlyNutrition Project. The participants concluded that there is a pressing need to harmonise the methodologies for assessing body composition, recognising that each has advantages and limitations. Essential core measurements across studies assessing early growth and body composition were identified, including weight, length, BMI, waist and mid-upper arm circumference, subscapular and triceps skinfold thicknesses, and bioelectrical impedance analysis. In research settings with access to more sophisticated technologies, additional methods could include dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, ultrasound assessment of regional body fat, magnetic resonance imaging (MRI), air displacement plethysmography (ADP), and deuterium dilution. These provide richer data to answer research questions in greater depth but also increase costs. Where overall whole-body composition is the primary outcome measure, ADP or tracer dilution should be used whenever possible. Where regional distribution of body fat is of greater interest, an imaging technique such as MRI is preferred.
Bipedal Behaviour in Olive Baboons: Infants versus Adults in a Captive Environment
Authors: Druelle François , Berillon Gilles
Published: August 2013

The olive baboon is described as a committed quadrupedal primate. However, available data show that they actually use a variety of locomotor and postural modes. Bipedalism is observed occasionally but spontaneously in captivity and in the wild. As observed in other Catarrhini, immature baboons appear to be more bipedal than adults: this study aims to provide the necessary quantitative data to support this hypothesis, as none has been available so far. The locomotor and postural repertoire was quantified for two age classes: infants beginning to forage independently, and adults. Our results show that infants appear to have a wider repertoire than adults, and bipedal postures and locomotion in infants, although infrequent, appear to distinguish them clearly from adults. In captivity, behavioural context and morphology are the two main factors that could explain age-related positional differences, given a constant ecological context.
Constipation in Patients with Thiamine Deficiency after Roux-en-Y Gastric Bypass Surgery
Authors: Shah Hiral N. , Bal Bikram S. , Finelli Frederick C. , Koch Timothy R.
Published: August 2013

Background/Aims: Roux-en-Y gastric bypass surgery is the most common bariatric surgery worldwide. We have described thiamine deficiency in patients with small intestinal bacterial overgrowth after gastric bypass. We hypothesized that symptoms of thiamine deficiency are common after gastric bypass. The aims of this study were to examine the prevalence of and treatment of symptoms of thiamine deficiency after gastric bypass. Methods: This is a prospective study performed in a large urban, community hospital. Consecutive gastric bypass patients seen from February 1, 2008 to May 1, 2009 are included. Thiamine deficiency in this study included both: consistent clinical symptoms and either (1) low blood thiamine level or (2) resolution of clinical symptoms after receiving thiamine. Results: Of 151 patients, 25 females and 2 males met the criteria for thiamine deficiency (prevalence of 18%). In these 27 patients, 12 had one symptom of thiamine deficiency, while 15 had symptoms consistent with multiple subtypes. Eleven patients reported constipation at 0.33-12 years (mean 4.8) after gastric bypass. Elevated serum folate levels were seen in 6 of 10 tested patients and there was an abnormal glucose-hydrogen breath test in 9 of 10 tested patients, supporting the presence of small intestinal bacterial overgrowth. Frequency of defecation improved after thiamine treatment. Conclusion: Thiamine deficiency resulting from small intestinal bacterial overgrowth should be considered in patients being seen for constipation after gastric bypass surgery.
Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity
Authors: Short Kirsty R. , Vissers Marloes , de Kleijn Stan , Zomer Aldert L. , Kedzierska Katherine , Grant Emma , Reading Patrick C. , Hermans Peter W.M. , Ferwerda Gerben , Diavatopoulos Dimitri A.
Published: August 2013

It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response.
Unusual Presentations of Type 2 Idiopathic Macular Telangiectasia
Authors: Atmani K. , Querques G. , Zourdani A. , Benhamou N. , Souied E.H.
Published: August 2013

Purpose: To report unusual presentations of type 2A idiopathic macular telangiectasia (IMT). Methods: A retrospective analysis of disease presentation was conducted in 32 patients with type 2A IMT. All patients underwent a complete ophthalmological examination, including spectral domain optical coherence tomography (SD-OCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results: Three out of 32 study patients showed the simultaneous presentation of type 2 IMT and other retinal diseases. In the first patient, the ophthalmological examination revealed a proliferative IMT associated with late-onset Stargardt disease. The second patient presented bilateral nonproliferative IMT and chronic serous chorioretinopathy in the left eye. The examination of the third patient revealed basal laminar drusen and soft drusen associated with IMT in both eyes. Conclusions: Type 2 IMT may represent an unusual presentation of Stargardt disease, chronic serous chorioretinopathy and basal laminar drusen. These presentations are most likely coincidental and highlight the importance of FA, ICGA and SD-OCT in the diagnosis and treatment of such cases.
Sinoatrial Node Reentry in a Canine Chronic Left Ventricular Infarct Model
Authors: Glukhov Alexey V. , Hage Lori T. , Hansen Brian J. , Pedraza-Toscano Adriana , Vargas-Pinto Pedro , Hamlin Robert L. , Weiss Raul , Carnes Cynthia A. , Billman George E. , Fedorov Vadim V.
Published: August 2013

Background—

Reentrant arrhythmias involving the sinoatrial node (SAN), namely SAN reentry, remain one of the most intriguing enigmas of cardiac electrophysiology. The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post–myocardial infarction (MI) structural remodeling.

Methods and Results—

In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post–left ventricular MI (6–15 weeks) dogs (n=5) compared with control dogs (n=4). In vitro, high-resolution near-infrared optical mapping of intramural SAN activation was performed in coronary perfused atrial preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16–28 mm) and micro-reentry (1–3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine [0.1 µmol/L] or isoproterenol [0.01–0.1 µmol/L]) after termination of atrial tachypacing (5–8 Hz), a finding not seen in controls. The autonomic stimulation induced heterogeneous changes in the SAN refractoriness; thus, competing atrial or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentry. The micro-reentry pivot waves were anchored to the longitudinal block region and produced both tachycardia and paradoxical bradycardia (due to exit block), despite an atrial ECG morphology identical to regular sinus rhythm. Intranodal longitudinal conduction blocks coincided with interstitial fibrosis strands that were exaggerated in the MI SAN pacemaker complex (fibrosis density: 37±7% MI versus 23±6% control;
P
<0.001).

Conclusions—

Both tachy- and brady-arrhythmias can result from SAN micro-reentry. Postinfarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry.
Transforming Growth Factor-β Signaling Promotes Pulmonary Hypertension Caused by
Schistosoma Mansoni
Authors: Graham Brian B. , Chabon Jacob , Gebreab Liya , Poole Jennifer , Debella Elias , Davis Laura , Tanaka Takeshi , Sanders Linda , Dropcho Nina , Bandeira Angela , Vandivier R. William , Champion Hunter C. , Butrous Ghazwan , Wang Xiao-Jing , Wynn Thomas A. , Tuder Rubin M.
Published: August 2013

Background—

The pathogenic mechanisms underlying pulmonary arterial hypertension resulting from schistosomiasis, one of the most common causes of pulmonary hypertension worldwide, remain unknown. We hypothesized that transforming growth factor-β (TGF-β) signaling as a consequence of Th2 inflammation is critical for the pathogenesis of this disease.

Methods and Results—

Mice sensitized and subsequently challenged with
Schistosoma mansoni
eggs developed pulmonary hypertension associated with an increase in right ventricular systolic pressure, thickening of the pulmonary artery media, and right ventricular hypertrophy. Rho-kinase–dependent vasoconstriction accounted for ≈60% of the increase in right ventricular systolic pressure. The pulmonary vascular remodeling and pulmonary hypertension were dependent on increased TGF-β signaling, as pharmacological blockade of the TGF-β ligand and receptor, and mice lacking Smad3 were significantly protected from
Schistosoma
-induced pulmonary hypertension. Blockade of TGF-β signaling also led to a decrease in interleukin-4 and interleukin-13 concentrations, which drive the Th2 responses characteristic of schistosomiasis lung pathology. Lungs of patients with schistosomiasis-associated pulmonary arterial hypertension have evidence of TGF-β signaling in their remodeled pulmonary arteries.

Conclusion—

Experimental
S mansoni
–induced pulmonary vascular disease relies on canonical TGF-β signaling.
Myocardial Reloading After Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis
Authors: Kajimoto Masaki , O'Kelly Priddy Colleen M. , Ledee Dolena R. , Xu Chun , Isern Nancy , Olson Aaron K. , Rosiers Christine Des , Portman Michael A.
Published: August 2013

Background

Extracorporeal membrane oxygenation (
ECMO
) unloads the heart, providing a bridge to recovery in children after myocardial stunning.
ECMO
also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with
ECMO
modulates both substrate entry into the citric acid cycle (
CAC
) and myocardial protein synthesis.

Methods and Results

Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8‐hour
ECMO
(
UNLOAD
) and postwean from
ECMO
(
RELOAD
). We infused into the coronary artery [2‐
13
C]‐pyruvate as an oxidative substrate and [
13
C
6
]‐L‐leucine as an indicator for amino acid oxidation and protein synthesis. Upon
RELOAD
, each functional parameter, which were decreased substantially by
ECMO
, recovered to near‐baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to
UNLOAD
,
RELOAD
altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl‐CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all
CAC
intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%).

Conclusions

RELOAD
alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the
CAC
. Improved understanding of factors governing these metabolic perturbations may serve as a basis for interventions and thereby improve success rate from weaning from
ECMO
.