bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent hypoxia: a low-risk research tool with therapeutic value in humans
Authors: Mateika Jason H. , El-Chami Mohamad , Shaheen David , Ivers Blake
Published: December 2014

Intermittent hypoxia has generally been perceived as a high-risk stimulus, particularly in the field of sleep medicine, because it is thought to initiate detrimental cardiovascular, respiratory, cognitive, and metabolic outcomes. In contrast, the link between intermittent hypoxia and beneficial outcomes has received less attention, perhaps because it is not universally understood that outcome measures following exposure to intermittent hypoxia may be linked to the administered dose. The present review is designed to emphasize the less recognized beneficial outcomes associated with intermittent hypoxia. The review will consider the role intermittent hypoxia has in cardiovascular and autonomic adaptations, respiratory motor plasticity, and cognitive function. Each section will highlight the literature that contributed to the belief that intermittent hypoxia leads primarily to detrimental outcomes. The second segment of each section will consider the possible risks associated with experimentally rather than naturally induced intermittent hypoxia. Finally, the body of literature indicating that intermittent hypoxia initiates primarily beneficial outcomes will be considered. The overarching theme of the review is that the use of intermittent hypoxia in research investigations, coupled with reasonable safeguards, should be encouraged because of the potential benefits linked to the administration of a variety of low-risk intermittent hypoxia protocols.
Nigral dopamine loss induces a global upregulation of presynaptic dopamine D1 receptor facilitation of the striatonigral GABAergic output
Authors: Ding Shengyuan , Li Li , Zhou Fu-Ming
Published: December 2014

In Parkinson's disease (PD), the dopamine (DA) neuron loss in the substantia nigra and the DA axon loss in the dorsal striatum are severe, but DA neurons in the ventral tegmental area and DA axons in middle and ventral striatal subregions are less affected. Severe DA loss leads to DA receptor supersensitivity, but it was not known whether the supersensitivity of the DA D1 receptors (D1Rs) on the striatonigral axon terminal is determined by the severe striatal or nigral DA loss. This question is important because these two possibilities affect the extent of the striatonigral terminals with supersensitive D1Rs and hence the strength of the direct pathway output. Here we have investigated this question in the transcription factor Pitx3 mutant mice that have a PD-like DA loss pattern. We found that the presynaptic D1R function was upregulated globally: the D1R-mediated facilitation was equally enhanced for the striatonigral GABA output originated in the dorsal striatum where the DA loss is severe and the somatic D1Rs are supersensitive, and for the striatonigral GABA output originated in the middle and ventral striatum where the DA loss is moderate and the somatic D1Rs are not supersensitive. These results suggest that severe nigral DA loss is sufficient to induce functional upregulation of the D1Rs on striatonigral axon terminals. Consequently, in PD, the globally enhanced D1Rs on striatonigral axon terminals originated in broad striatal subregions may strongly enhance the striatonigral GABA output upon D1R stimulation, potentially contributing to D1R agonism's profound motor-stimulating effects.
Influence of developmental nicotine exposure on spike-timing precision and reliability in hypoglossal motoneurons
Authors: Powell Gregory L. , Levine Richard B. , Frazier Amanda M. , Fregosi Ralph F.
Published: December 2014

Smoothly graded muscle contractions depend in part on the precision and reliability of motoneuron action potential generation. Whether or not a motoneuron generates spikes precisely and reliably depends on both its intrinsic membrane properties and the nature of the synaptic input that it receives. Factors that perturb neuronal intrinsic properties and/or synaptic drive may compromise the temporal precision and the reliability of action potential generation. We have previously shown that developmental nicotine exposure (DNE) alters intrinsic properties and synaptic transmission in hypoglossal motoneurons (XIIMNs). Here we show that the effects of DNE also include alterations in spike-timing precision and reliability, and spike-frequency adaptation, in response to sinusoidal current injection. Current-clamp experiments in brainstem slices from neonatal rats show that DNE lowers the threshold for spike generation but increases the variability of spike-timing mechanisms. DNE is also associated with an increase in spike-frequency adaptation and reductions in both peak and steady-state firing rate in response to brief, square wave current injections. Taken together, our data indicate that DNE causes significant alterations in the input-output efficiency of XIIMNs. These alterations may play a role in the increased frequency of obstructive apneas and altered suckling strength and coordination observed in nicotine-exposed neonatal humans.
Diagrammatic Analysis of Nonhomogeneous Diffusion
Authors: Hernández Julio A.
Published: December 2014

By virtue of its complexity, realistic approaches to describe diffusion in cellular media require the employment of computational methods. Among others, this type of studies has shown that the apparent diffusion coefficient of a macromolecular solute through a cytoplasmic-like medium exhibits a power-law dependence with the excluded volume. Power laws are ubiquitous findings in diverse systems, such as metabolic processes, population dynamics, and communication networks, and have been the object of many interpretative formal approaches. This study introduces a diagrammatic algorithm, inspired in previous ones employed to analyze multicyclic chemical systems, to derive expressions for nonhomogeneous diffusion coefficients and to study the effects of volume exclusion. A most noteworthy result of this work is that midsize diagrams of nonhomogeneous diffusion are already able to exhibit an approximate power-law dependence of the diffusion coefficient with the excluded volume. The employment of the diagrammatic method for the analysis of simple situations may thus prove useful to interpret some properties of larger network systems.
Selective Migration of Subpopulations of Bone Marrow Cells along an SDF-1α and ATP Gradient
Authors: Laupheimer Michael , Skorska Anna , Große Jana , Tiedemann Gudrun , Steinhoff Gustav , David Robert , Lux Cornelia A.
Published: December 2014

Both stem cell chemokine stromal cell-derived factor-1α (SDF-1α) and extracellular nucleotides such as adenosine triphosphate (ATP) are increased in ischemic myocardium. Since ATP has been reported to influence cell migration, we analysed the migratory response of bone marrow cells towards a combination of SDF-1 and ATP. Total nucleated cells (BM-TNCs) were isolated from bone marrow of cardiac surgery patients. Migration assays were performed in vitro. Subsequently, migrated cells were subjected to multicolor flow cytometric analysis of CD133, CD34, CD117, CD184, CD309, and CD14 expression. BM-TNCs migrated significantly towards a combination of SDF-1 and ATP. The proportions of CD34+ cells as well as subpopulations coexpressing multiple stem cell markers were selectively enhanced after migration towards SDF-1 or SDF-1 + ATP. After spontaneous migration, significantly fewer stem cells and CD184+ cells were detected. Direct incubation with SDF-1 led to a reduction of CD184+ but not stem cell marker-positive cells, while incubation with ATP significantly increased CD14+ percentage. In summary, we found that while a combination of SDF-1 and ATP elicited strong migration of BM-TNCs in vitro, only SDF-1 was responsible for selective attraction of hematopoietic stem cells. Meanwhile, spontaneous migration of stem cells was lower compared to BM-TNCs or monocytes.
350 nm Broadband Supercontinuum Generation Using Dispersion Engineered Near Zero Ultraflat Square-Lattice PCF around 1.55 μm and Fabrication Tolerance Analysis
Authors: Maji Partha Sona , Roy Chaudhuri Partha
Published: December 2014

In this work, a new design of ultraflat dispersion PCF based on square-lattice geometry with all uniform air holes towards broadband smooth SCG around the C-band of wavelength has been presented. The air hole of the inner ring was infiltrated with liquid of certain refractive indices. Numerical investigations establish a near zero ultraflattened dispersion of 0 ± 0.78 ps/nm/km in a wavelength range of 1496 nm to 2174 nm (678 nm bandwidth) covering most of the communications bands with the first zero dispersion wavelength around 1.54 μm. With the optimized ultraflattened fiber, we have achieved a broadband SC spectrum with FWHM of 350 nm with the central wavelength of 1550 nm with less than a meter long of the fiber by using a picosecond pulse laser. We have also analyzed the sensitivity of the optimized dispersion design by small variations from the optimum value of the geometrical structural parameters. Our investigations establish that for a negative change of PCF parameters, the profile retains the smooth and flat SCG spectra; however, for a positive change, the smooth and a flat spectrum is lost. The new design of the fiber will be capable of covering huge diverse field of DWDM sources, spectroscopy, meteorology, optical coherence tomography, and optical sensing.
Bioethanol from Lignocellulosic Biomass: Current Findings Determine Research Priorities
Authors: Kang Qian , Appels Lise , Tan Tianwei , Dewil Raf
Published: December 2014

“Second generation” bioethanol, with lignocellulose material as feedstock, is a promising alternative for first generation bioethanol. This paper provides an overview of the current status and reveals the bottlenecks that hamper its implementation. The current literature specifies a conversion of biomass to bioethanol of 30 to ~50% only. Novel processes increase the conversion yield to about 92% of the theoretical yield. New combined processes reduce both the number of operational steps and the production of inhibitors. Recent advances in genetically engineered microorganisms are promising for higher alcohol tolerance and conversion efficiency. By combining advanced systems and by intensive additional research to eliminate current bottlenecks, second generation bioethanol could surpass the traditional first generation processes.
Effect of Sintering Temperature on Structural and Morphological Properties of Europium (III) Oxide Doped Willemite
Authors: Syamimi Nur Fatin , Amin Matori Khamirul , Lim Way Foong , Abdul Aziz Sidek , Mohd Zaid Mohd Hafiz
Published: December 2014

Willemite- (Zn2SiO4-) based glass ceramics doped with various amounts of europium oxide (Eu2O3) were prepared by solid state melting and quenching method. Effect of sintering temperature (600–1000°C) on structural and morphological properties of the doped samples was investigated. Phase composition, phase evolution, functional groups, and microstructure analysis were, respectively, characterized using X-ray diffractometer (XRD), fourier transform infrared spectroscopy, field emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray. XRD analysis detected the presence of rhombohedral crystalline phase in the doped samples sintered at different temperatures. FE-SEM and bulk density results confirmed that doping of the willemite with Eu2O3effectively enhanced densification. The microstructural analysis of the doped samples showed that the average grain size increased with the increase of sintering temperature.
Laparoscopic Watson Fundoplication Is Effective and Durable in Children with Gastrooesophageal Reflux
Authors: Dunckley Matthew G. , Rajwani Kapil M. , Mahomed Anies A.
Published: December 2014

Gastroesophageal reflux (GOR) affects 2–8% of children over 3 years of age and is associated with significant morbidity. The disorder is particularly critical in neurologically impaired children, who have a high risk of aspiration. Traditionally, the surgical antireflux procedure of choice has been Nissen’s operation. However, this technique has a significant incidence of mechanical complications and has a reoperation rate of approximately 7%, leading to the development of alternative approaches. Watson’s technique of partial anterior fundoplication has been shown to achieve long-lasting reflux control in adults with few mechanical complications, but there is limited data in the paediatric population. We present here short- and long-term outcomes of laparoscopic Watson fundoplication in a series of 76 children and infants, 34% of whom had a degree of neurological impairment including severe cerebral palsy and hypoxic brain injury. The overall complication rate was 27.6%, of which only 1 was classified as major. To date, we have not recorded any incidences of perforation and no revisions. In our experience, Watson’s laparoscopic partial fundoplication can be performed with minimal complications and with durable results, not least in neurologically compromised children, making it a viable alternative to the Nissen procedure in paediatric surgery.
Almost Automorphic Functions of Ordernand Applications to Dynamic Equations on Time Scales
Authors: Mophou Gisèle , N’Guérékata Gaston Mandata , Milce Aril
Published: December 2014

We revisit the notion on almost automorphic functions on time scales given by Lizama and Mesquita (2013). Then we present the notion of almost automorphic functions of ordern. Finally, we apply this notion to study the existence and uniqueness and the global stability of almost automorphic solution of first order to a dynamical equation with finite time varying delay.
Context Transfer in Reinforcement Learning Using Action-Value Functions
Authors: Mousavi Amin , Nadjar Araabi Babak , Nili Ahmadabadi Majid
Published: December 2014

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents’ MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework isQ-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. TheQ-values learned during the learning process of the source tasks are mapped to the sets ofQ-values for the target task. These transferredQ-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task.
In Situ Dispersive EXAFS in Electrocatalysis: The Investigation of the Local Structure of IrOxin Chronoamperometric Conditions as a Case Study
Authors: Achilli Elisabetta , Minguzzi Alessandro , Lugaresi Ottavio , Locatelli Cristina , Rondinini Sandra , Spinolo Giorgio , Ghigna Paolo
Published: December 2014

An in situ study with dispersive EXAFS (Extended X-Ray Absorption Spectroscopy) at the Ir-LIIIedge is performed to characterize Electrodeposited Iridium Oxide Films (EIROF) under chronoamperometric conditions. The technique monitors the local chemical environment and electronic structure of iridium during the oxidation of Ir(III) to Ir(IV) with a time resolution of milliseconds. The study is performed in both acidic and basic media. The Fourier transforms of the time-resolved EXAFS signals clearly show that the short-range structure of Ir is similar to that of rutile-type IrO2and is maintained during the reaction, thus accounting for the flexibility of the structure of the electrode material in accommodating different oxidation states. From a more general point of view, the work demonstrates the capabilities of in situ experiments based on state-of-the-art dispersive EXAFS in clarifying the mechanistic aspects of electrochemical processes.
County-Scale Spatial Distribution of Soil Enzyme Activities and Enzyme Activity Indices in Agricultural Land: Implications for Soil Quality Assessment
Authors: Tan Xiangping , Xie Baoni , Wang Junxing , He Wenxiang , Wang Xudong , Wei Gehong
Published: December 2014

Here the spatial distribution of soil enzymatic properties in agricultural land was evaluated on a county-wide (567 km2) scale in Changwu, Shaanxi Province, China. The spatial variations in activities of five hydrolytic enzymes were examined using geostatistical methods. The relationships between soil enzyme activities and other soil properties were evaluated using both an integrated total enzyme activity index (TEI) and the geometric mean of enzyme activities (GME). At the county scale, soil invertase, phosphatase, and catalase activities were moderately spatially correlated, whereas urease and dehydrogenase activities were weakly spatially correlated. Correlation analysis showed that both TEI and GME were better correlated with selected soil physicochemical properties than single enzyme activities. Multivariate regression analysis showed that soil OM content had the strongest positive effect while soil pH had a negative effect on the two enzyme activity indices. In addition, total phosphorous content had a positive effect on TEI and GME in orchard soils, whereas alkali-hydrolyzable nitrogen and available potassium contents, respectively, had negative and positive effects on these two enzyme indices in cropland soils. The results indicate that land use changes strongly affect soil enzyme activities in agricultural land, where TEI provides a sensitive biological indicator for soil quality.
Mechanical Properties of Membranes of Poly(L-co-DL-lactic acid) with Poly(caprolactone triol) and StudyIn Vivo
Authors: Duarte Marcia Adriana Tomaz , Motta Adriana Cristina , Duek Eliana Aparecida de Rezende
Published: December 2014

There is increasing interest in aliphatic polyesters from lactones and lactides because of their biodegradability and biocompatibility. Among these compounds, poly(lactide), and poly(glycolide), poly(ε-caprolactone) and their copolymers are especially interesting because of their potential applications as biomedical materials. The aim of this study was to examine the properties of membranes of poly(L-co-D,L lactic acid) (PLDLA) with poly(caprolactone triol) (PCL-T) obtained by solvent evaporation. The blends were characterized by differential scanning calorimetry, dynamic mechanical analysis, Fourier transform infrared spectroscopy, and tensile strength tests. Based on the results ofin vitrostudies, PLDLA/PCL-T blends of 100/0 and 90/10 were implanted in subcutaneous tissue of Wistar rats for 1, 3, 7, 15, and 60 days to evaluate their biocompatibility. Histological analysis indicated that, although PCL-T-containing membranes caused a more prominent inflammatory reaction in the initial time intervals, by 60 days after implantation, the material was surrounded by dense, organized collagen with almost no inflammatory infiltrate.
Online Identification Methods of Load Rotary Inertia and Torque in Radar Servo System
Authors: Chen Yong , Liu Xia , Zhou Hu
Published: December 2014

In radar servo system, the load is usually subject to movement and gust, which may cause instability of the system. In this paper, the online identification methods of load rotary inertia and torque in radar servo system are proposed, respectively. The radar servo system is based on synchronous motor. The load rotary inertia of the system is identified online by a disturbance observer. Moreover, a reduced order Luenberger observer is designed to observe the variation of the load torque and velocity online. The simulation models are established to verify the proposed disturbance observer for the load rotary inertia and the reduced order Luenberger observer for the load torque and velocity.
Vaccines for Canine Leishmaniasis
Authors: Foroughi-Parvar Faeze , Hatam Gholamreza
Published: December 2014

Leishmania infantumis the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL). The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL) is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.
Design of Commute Carpooling Based on Fixed Time and Routes
Authors: Zhou Guiliang , Huang Kai , Mao Lina
Published: December 2014

Although the private carpooling market of China has grown rapidly, it has been embarrassed by problems such as obstructed information, disordered expense, and frequent crimes currently. In this paper, a commute carpooling program based on fixed time and routes is designed and corresponding carpooling information platform is built to realize information retrieval, information matching, and mutual selection and evaluation. We have practiced the program in Huaian, China, and then evaluated it using the improved time-expense impedance model and VISSIM simulation system. The result shows that the carpooling program can reduce 65%~86% of the time-expense impedance and optimize some network parameters up to 20%~40%. Since it will help in reducing the travel time and cost greatly, improving safety and economy during carpooling, and easing the traffic congestion, it is a worthy carpooling mode to be extended in China.
On the Designing, Efficiency, and Stirring Force of an Induction Coil for the Processing of Prototype Al Based Nanocomposites
Authors: Mansoor Muhammad , Shahid Muhammad
Published: December 2014

Induction melting could be a potential fabrication method for aluminum matrix nanocomposites, owing to its characteristics stirring action and rapid heating. In the present work, an induction coil for small scale composite fabrication was designed through geometric, thermal, and electromagnetic analyses. Subsequently, the designed coil was simulated for its thermal efficiency and stirring force using finite element method magnetics software. The designed coil yielded more than 60% of the total energy supplied into thermal efficiency with a stirring force <3 mN, which could be significant for efficient melting and stirring to fabricate the aluminum matrix nanocomposites.
Response of Short Duration Tropical Legumes and Maize to Water Stress: A Glasshouse Study
Authors: Sohrawardy Hossain , Hossain Md. Lokman
Published: December 2014

The study was conducted as a pot experiment in the tropical glasshouse to evaluate the response of grain legumes (Phaseolus vulgaris, Vigna unguiculata, andLablab purpureus) in comparison to maize (Zea mays) and estimate their potential and performance. Two experiments were established using completely randomized design. Physiological measurements (stomatal conductance, photosynthetic activities, and transpiration rates) were measured using LCpro instrument. Scholander bomb was used for the measurement of plant cell water potential. Significant difference was observed in different plant species with increase of different water regimes. Among the legumes,L. purpureusshowed better response in water stressed conditions. At the beginning, in dry watered treatment the photosynthetic rate was below 0 µmol m−2 s−1and in fully watered condition it was 48 µmol m−2 s−1. In dry treatment, total dry weight was 10 g/pot and in fully watered condition it was near to 20 g/pot inP. vulgaris. The study concludes that water stress condition should be taken into consideration for such type of crop cultivation in arid and semiarid regions.
Mass Screening of Vision in the Cinemas and a Maculascope for the Masses: Revival of Haidinger’s Brush
Authors: Avudainayagam Kodikullam V. , Avudainayagam Chitralekha S.
Published: December 2014

Haidinger’s brush, an entoptic phenomenon, is very useful in checking central vision loss and eccentric fixation. Haidinger’s brush is also used to provide vision training for subjects affected by eccentric fixation/lazy eye. We propose the use of Haidinger’s brush for mass self-screening of vision in cinema theatres in one go and at no cost to the subjects. We also suggest a simple projection technology for mass vision screening of subjects in waiting rooms or at shop windows of eye-care practitioners. Finally, we propose a new affordable handheld device for vision training. The test and the devices that we propose would increase public awareness of eye health, improve vision in children, and help prevent blindness in the elderly.
Using Multivariate Geostatistics to Assess Patterns of Spatial Dependence of Apparent Soil Electrical Conductivity and Selected Soil Properties
Authors: Siqueira Glécio Machado , Dafonte Jorge Dafonte , Valcárcel Armesto Montserrat , Silva Ênio Farias França e
Published: December 2014

The apparent soil electrical conductivity (ECa) was continuously recorded in three successive dates using electromagnetic induction in horizontal (ECa-H) and vertical (ECa-V) dipole modes at a 6 ha plot located in Northwestern Spain. One of the ECadata sets was used to devise an optimized sampling scheme consisting of 40 points. Soil was sampled at the 0.0–0.3 m depth, in these 40 points, and analyzed for sand, silt, and clay content; gravimetric water content; and electrical conductivity of saturated soil paste. Coefficients of correlation between ECaand gravimetric soil water content (0.685 for ECa-V and 0.649 for ECa-H) were higher than those between ECaand clay content (ranging from 0.197 to 0.495, when different ECarecording dates were taken into account). Ordinary and universal kriging have been used to assess the patterns of spatial variability of the ECadata sets recorded at successive dates and the analyzed soil properties. Ordinary and universal cokriging methods have improved the estimation of gravimetric soil water content using the data of ECaas secondary variable with respect to the use of ordinary kriging.
Effect of Catalytic Pyrolysis Conditions Using Pulse Current Heating Method on Pyrolysis Products of Wood Biomass
Authors: Honma Sensho , Hata Toshimitsu , Watanabe Takashi
Published: December 2014

The influence of catalysts on the compositions of char and pyrolysis oil obtained by pyrolysis of wood biomass with pulse current heating was studied. The effects of catalysts on product compositions were analyzed using GC-MS and TEM. The compositions of some aromatic compounds changed noticeably when using a metal oxide species as the catalyst. The coexistence or dissolution of amorphous carbon and iron oxide was observed in char pyrolyzed at 800°C with Fe3O4. Pyrolysis oil compositions changed remarkably when formed in the presence of a catalyst compared to that obtained from the uncatalyzed pyrolysis of wood meal. We observed a tendency toward an increase in the ratio of polyaromatic hydrocarbons in the pyrolysis oil composition after catalytic pyrolysis at 800°C. Pyrolysis of biomass using pulse current heating and an adequate amount of catalyst is expected to yield a higher content of specific polyaromatic compounds.
Performance of All-Optical XNOR Gate Based on Two-Photon Absorption in Semiconductor Optical Amplifiers
Authors: Kotb Amer
Published: December 2014

All-optical logic XNOR gate is realized by a series combination of XOR and INVERT gates. This Boolean function is realized by using Mach-Zehnder interferometers (MZIs) and exploiting the nonlinear effect of two-photon absorption (TPA) in semiconductor optical amplifiers (SOAs). The employed model takes into account the impact of amplified spontaneous emission (ASE), input pulse energy, pulsewidth, SOAs carrier lifetime, and linewidth enhancement factor (α-factor) on the gate’s output quality factor (Q-factor). The outcome of this study shows that the all-optical XNOR gate is indeed feasible with the proposed scheme at 250 Gb/s with both logical correctness and acceptable quality.
Chitosan Hydrogels for Chondroitin Sulphate Controlled Release: An Analytical Characterization
Authors: Bianchera Annalisa , Salomi Enrico , Pezzanera Matteo , Ruwet Elisabeth , Bettini Ruggero , Elviri Lisa
Published: December 2014

This paper provides an analytical characterization of chitosan scaffolds obtained by freeze-gelation toward the uptake and the controlled release of chondroitin sulphate (CS), as cartilage repair agent, under different pH conditions. Scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and liquid chromatography-UV spectrophotometry (LC-UV) techniques were exploited to obtain qualitative and quantitative descriptions of polymer and drug behaviour in the biomaterial. As for morphology, SEM analysis allowed the evaluation of scaffold porosity in terms of pore size and distribution both at the surface (Feret diameter58±19 μm) and on the cross section (Feret diameter106±51 μm). LC and ATR-FTIR evidenced a pH-dependent CS loading and release behaviour, strongly highlighting the role of electrostatic forces on chitosan/chondroitin sulphate interactions.
A Novel 3D Imaging Method for Airborne Downward-Looking Sparse Array SAR Based on Special Squint Model
Authors: Ren Xiaozhen , Qin Yao , Qiao Lihong
Published: December 2014

Three-dimensional (3D) imaging technology based on antenna array is one of the most important 3D synthetic aperture radar (SAR) high resolution imaging modes. In this paper, a novel 3D imaging method is proposed for airborne down-looking sparse array SAR based on the imaging geometry and the characteristic of echo signal. The key point of the proposed algorithm is the introduction of a special squint model in cross track processing to obtain accurate focusing. In this special squint model, point targets with different cross track positions have different squint angles at the same range resolution cell, which is different from the conventional squint SAR. However, after theory analysis and formulation deduction, the imaging procedure can be processed with the uniform reference function, and the phase compensation factors and algorithm realization procedure are demonstrated in detail. As the method requires only Fourier transform and multiplications and thus avoids interpolations, it is computationally efficient. Simulations with point scatterers are used to validate the method.
Decision Feedback Blind Equalizer with Tap-Leaky Whitening for Stable Structure-Criterion Switching
Authors: Krstić Vladimir R. , Dukić Miroslav L.
Published: December 2014

The research presented in this paper improves the structure-criterion switching performance of the blind decision feedback equalizer (DFE) which eliminates error propagation effects by optimizing both the structure and the cost criterion. To conquer the complexity of the 64-QAM (quadrature amplitude modulated) signal constellation, the stochastic entropy-gradient algorithm is additionally regularized by the coefficient leaky term to avoid a coefficients norm overgrowth of the received signal whitener. Effectively, the leak of coefficients is employed to ensure a stable structure-criterion switching of DFE between blind and decision-directed operation modes. The optimization of the resulting whitening algorithm is achieved by means of two free, leaky and entropic, parameters which act in opposition to each other. Both, the influence of the 64-QAM signal on the feedback filter behavior and the parametric optimization of the whitening algorithm are analyzed through simulations.
Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy
Authors: Lee Hye Won , Lee Jung-il , Lee Se Jeong , Cho Hyun Jung , Song Hye Jin , Jeong Da Eun , Seo Yun Jee , Shin Sang , Joung Je-Gun , Kwon Yong-Jun , Choi Yoon-La , Park Woong-Yang , Lee Hyun Moo , Seol Ho Jun , Shim Young Mog , Joo Kyeung Min , Nam Do-Hyun
Published: December 2014

Purpose: The increasing prevalence of distant metastases from non–small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies.

Experimental Design: We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment.

Results: NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions.

Conclusions: Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. Clin Cancer Res; 21(5); 1172–82. ©2014 AACR.
Extreme Concentrations of Endogenous Sex Hormones, Ischemic Heart Disease, and Death in Women
Authors: Benn Marianne , Voss Sidsel Skou , Holmegard Haya N. , Jensen Gorm B. , Tybjærg-Hansen Anne , Nordestgaard Børge G.
Published: December 2014

Objective—

Sex hormones may be critical determinants of ischemic heart disease and death in women, but results from previous studies are conflicting. To clarify this, we tested the hypothesis that extreme plasma concentrations of endogenous estradiol and testosterone are associated with risk of ischemic heart disease and death in women.

Approach and Results—

In a nested prospective cohort study, we measured plasma estradiol in 4600 and total testosterone in 4716 women not receiving oral contraceptives or hormonal replacement therapy from the 1981 to 1983 examination of the Copenhagen City Heart Study. During ≤30 years of follow-up, 1013 women developed ischemic heart disease and 2716 died. In women with a plasma estradiol below the fifth percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk of ischemic heart disease was 44% (95% confidence interval, 14%–81%) higher; however, plasma estradiol concentrations did not associate with death. Also, in women with a plasma testosterone concentration at or above the 95th percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk was 68% (34%–210%) higher for ischemic heart disease, 36% (18%–58%) higher for any death, and 38% (15%–65%) higher for death from other causes than cardiovascular disease and cancer. These results were similar for postmenopausal women alone.

Conclusions—

In women, extreme low concentrations of endogenous estradiol were associated with high risk of ischemic heart disease, and extreme high concentrations of endogenous testosterone were associated with high risk of ischemic heart disease and death.
MEF2B-Nox1 Signaling Is Critical for Stretch-Induced Phenotypic Modulation of Vascular Smooth Muscle Cells
Authors: Rodríguez Andrés I. , Csányi Gábor , Ranayhossaini Daniel J. , Feck Douglas M. , Blose Kory J. , Assatourian Lillian , Vorp David A. , Pagano Patrick J.
Published: December 2014

Objective—

Blood vessel hemodynamics have profound influences on function and structure of vascular cells. One of the main mechanical forces influencing vascular smooth muscle cells (VSMC) is cyclic stretch (CS). Increased CS stimulates reactive oxygen species (ROS) production in VSMC, leading to their dedifferentiation, yet the mechanisms involved are poorly understood. This study was designed to test the hypothesis that pathological CS stimulates NADPH oxidase isoform 1 (Nox1)–derived ROS via MEF2B, leading to VSMC dysfunction via a switch from a contractile to a synthetic phenotype.

Approach and Results—

Using a newly developed isoform-specific Nox1 inhibitor and gene silencing technology, we demonstrate that a novel pathway, including MEF2B-Nox1-ROS, is upregulated under pathological stretch conditions, and this pathway promotes a VSMC phenotypic switch from a contractile to a synthetic phenotype. We observed that CS (10% at 1 Hz) mimicking systemic hypertension in humans increased Nox1 mRNA, protein levels, and enzymatic activity in a time-dependent manner, and this upregulation was mediated by MEF2B. Furthermore, we show that stretch-induced Nox1-derived ROS upregulated a specific marker for synthetic phenotype (osteopontin), whereas it downregulated classical markers for contractile phenotype (calponin1 and smoothelin B). In addition, our data demonstrated that stretch-induced Nox1 activation decreases actin fiber density and augments matrix metalloproteinase 9 activity, VSMC migration, and vectorial alignment.

Conclusions—

These results suggest that CS initiates a signal through MEF2B that potentiates Nox1-mediated ROS production and causes VSMC to switch to a synthetic phenotype. The data also characterize a new Nox1 inhibitor as a potential therapy for treatment of vascular dysfunction in hypertension.
Exercise Oscillatory Ventilation in Patients With Fontan Physiology
Authors: Nathan Ashwin S. , Loukas Brittani , Moko Lilamarie , Wu Fred , Rhodes Jonathan , Rathod Rahul H. , Systrom David M. , Ubeda Tikkanen Ana , Shafer Keri , Lewis Gregory D. , Landzberg Michael J. , Opotowsky Alexander R.
Published: December 2014

Background—

Exercise oscillatory ventilation (EOV) refers to regular oscillations in minute ventilation (V
E
) during exercise. Its presence correlates with heart failure severity and worse prognosis in adults with acquired heart failure. We evaluated the prevalence and predictive value of EOV in patients with single ventricle Fontan physiology.

Methods and Results—

We performed a cross-sectional analysis and prospective survival analysis of patients who had undergone a Fontan procedure and subsequent cardiopulmonary exercise test. Data were reviewed for baseline characteristics and incident mortality, heart transplant, or nonelective cardiovascular hospitalization. EOV was defined as regular oscillations for >60% of exercise duration with amplitude >15% of average V
E
. Survival analysis was performed using Cox regression. Among 253 subjects, EOV was present in 37.5%. Patients with EOV were younger (18.8±9.0 versus 21.7±10.1 years;
P
=0.02). EOV was associated with higher New York Heart Association functional class (
P
=0.02) and V
E
/V
CO
2
slope (36.8±6.9 versus 33.7±5.7;
P
=0.0002), but not with peak V
O
2
(59.7±14.3 versus 61.0±16.0% predicted;
P
=0.52) or noninvasive measures of cardiac function. The presence of EOV was associated with slightly lower mean cardiac index but other invasive hemodynamic variables were similar. During a median follow-up of 5.5 years, 22 patients underwent transplant or died (n=19 primary deaths, 3 transplants with 2 subsequent deaths). EOV was associated with increased risk of death or transplant (hazard ratio, 3.9; 95% confidence interval, 1.5–10.0;
P
=0.002) and also predicted the combined outcome of death, transplant, or nonelective cardiovascular hospitalization after adjusting for New York Heart Association functional class, peak V
O
2
, and other covariates (multivariable hazard ratio, 2.0; 95% confidence interval, 1.2–3.6;
P
=0.01).

Conclusions—

EOV is common in the Fontan population and strongly predicts lower transplant-free survival.
Tumor Necrosis Factor
Authors: Duerrschmid Clemens , Trial JoAnn , Wang Yanlin , Entman Mark L. , Haudek Sandra B.
Published: December 2014

Background—

Continuous angiotensin-II infusion induced the uptake of monocytic fibroblast precursors that initiated the development of cardiac fibrosis; these cells and concurrent fibrosis were absent in mice lacking tumor necrosis factor receptor 1 (TNFR1). We now investigated their cellular origin and temporal uptake and the involvement of TNFR1 in monocyte-to-fibroblast differentiation.

Methods and Results—

Within a day, angiotensin-II induced a proinflammatory environment characterized by production of inflammatory chemokines, cytokines, and T
H
1-interleukins and uptake of bone marrow-derived M1 cells. After a week, the cardiac environment changed to profibrotic with growth factor and T
H
2-interleukin synthesis, uptake of bone marrow–derived M2 cells, and the presence of M2-related fibroblasts. TNFR1 signaling was not necessary for early M1 uptake, but its absence diminished the amount of M2 cells. TNFR1-knockout hearts also showed reduced levels of cytokine expression, but not of T
H
-related lymphokines. Reconstitution of wild-type bone marrow into TNFR1-knockout mice was sufficient to restore M2 uptake, upregulation of proinflammatory and profibrotic genes, and development of fibrosis in response to angiotensin-II. We also developed an in vitro mouse monocyte-to-fibroblast maturation assay that confirmed the essential role of TNFR1 in the sequential progression of monocyte activation and fibroblast formation.

Conclusions—

Development of cardiac fibrosis in response to angiotensin-II was mediated by myeloid precursors and consisted of 2 stages. A primary M1 inflammatory response was followed by a subsequent M2 fibrotic response. Although the first phase seemed to be independent of TNFR1 signaling, the later phase (and development of fibrosis) was abrogated by deletion of TNFR1.
Ectopic Fat Depots and Left Ventricular Function in Nondiabetic Men With Nonalcoholic Fatty Liver Disease
Authors: Granér Marit , Nyman Kristofer , Siren Reijo , Pentikäinen Markku O. , Lundbom Jesper , Hakkarainen Antti , Lauerma Kirsi , Lundbom Nina , Nieminen Markku S. , Taskinen Marja-Riitta
Published: December 2014

Background—

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease.

Methods and Results—

Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function.

Conclusions—

Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study.
Cardio-Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Reveals Molecular Signatures of Endogenous Fibrosis and Exogenous Contrast Media
Authors: Vandsburger Moriel , Vandoorne Katrien , Oren Roni , Leftin Avigdor , Mpofu Senzeni , Delli Castelli Daniela , Aime Silvio , Neeman Michal
Published: December 2014

Background—

Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST).

Methods and Results—

Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space.

Conclusions—

cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans.
Cardiac MyBP-C Regulates the Rate and Force of Contraction in Mammalian Myocardium
Authors: Moss Richard L. , Fitzsimons Daniel P. , Ralphe J. Carter
Published: December 2014

Cardiac myosin–binding protein-C (cMyBP-C) is a thick filament-associated protein that seems to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both. Several studies over the past several years have suggested that the interactions of cardiac myosin–binding protein-C with its binding partners vary with its phosphorylation state, binding predominantly to myosin when dephosphorylated and to actin when it is phosphorylated by protein kinase A or other kinases. Here, we summarize evidence suggesting that phosphorylation of cardiac myosin binding protein-C is a key regulator of the kinetics and amplitude of cardiac contraction during β-adrenergic stimulation and increased stimulus frequency. We propose a model for these effects via a phosphorylation-dependent regulation of the kinetics and extent of cooperative recruitment of cross bridges to the thin filament: phosphorylation of cardiac myosin binding protein-C accelerates cross bridge binding to actin, thereby accelerating recruitment and increasing the amplitude of the cardiac twitch. In contrast, enhanced lusitropy as a result of phosphorylation seems to be caused by a direct effect of phosphorylation to accelerate cross-bridge detachment rate. Depression or elimination of one or both of these processes in a disease, such as end-stage heart failure, seems to contribute to the systolic and diastolic dysfunction that characterizes the disease.