bluuebunny/crossref_metadata_2025 huggingface dataset:
GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy
Authors: Li Mengjie , Wang Xufang , Aa Jiye , Qin Weisong , Zha Weibin , Ge Yongchun , Liu Linsheng , Zheng Tian , Cao Bei , Shi Jian , Zhao Chunyan , Wang Xinwen , Yu Xiaoyi , Wang Guangji , Liu Zhihong
Published: March 2013

Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.
A Bayesian approach for characterizing direction tuning curves in the supplementary motor area of behaving monkeys
Authors: Taubman Hadas , Vaadia Eilon , Paz Rony , Chechik Gal
Published: March 2013

Neural responses are commonly studied in terms of “tuning curves,” characterizing changes in neuronal response as a function of a continuous stimulus parameter. In the motor system, neural responses to movement direction often follow a bell-shaped tuning curve for which the exact shape determines the properties of neuronal movement coding. Estimating the shape of that tuning curve robustly is hard, especially when directions are sampled unevenly and at a coarse resolution. Here, we describe a Bayesian estimation procedure that improves the accuracy of curve-shape estimation even when the curve is sampled unevenly and at a very coarse resolution. Using this approach, we characterize the movement direction tuning curves in the supplementary motor area (SMA) of behaving monkeys. We compare the SMA tuning curves to tuning curves of neurons from the primary motor cortex (M1) of the same monkeys, showing that the tuning curves of the SMA neurons tend to be narrower and shallower. We also show that these characteristics do not depend on the specific location in each region.
Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia miltiorrhizaandPueraria lobata) in High-Risk Hypertension
Authors: Woo K. S. , Yip Thomas W. C. , Chook Ping , Kwong S. K. , Szeto C. C. , Li June K. Y. , Yu Alex W. Y. , Cheng William K. F. , Chan Thomas Y. K. , Fung K. P. , Leung P. C.
Published: March 2013

Introduction. Hypertension in association with diabetes (DM), renal impairment (RI), and left ventricular hypertrophy (LVH) increases the risk of future cardiovascular events. We hypothesize, traditional herbal medicines Danshen and Gegen (D&G) have beneficial effects on atherogenesis in these high-risk hypertensive subjects.Subjects and Methods. 90 asymptomatic hypertensive subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. All data were analyzed using the Statistical Package for Social Sciences in Windows 16.0.Results. Their mean age was55±8years, and 74.4% were male. After 12 months of adjunctive therapies and compared with baseline, there were no significant changes in blood pressure, heart rate, hematological, glucose, and creatinine profiles in both placebo and D&G groups. FMD improved significantly during D&G (P=0.0001) and less so after placebo treatment (P=0.001). There was a mild but significant decrease in carotid IMT after D&G (P<0.001) but no significant changes after placebo. A trend of better improvement in FMD after higher versus lower D&G dosages was seen. D&G were well tolerated, with no significant adverse events or blood biochemistry changes.Conclusion. D&G adjunctive treatment was well tolerated and significantly improved atherogenesis in high-risk hypertensive patients, with potential in primary atherosclerosis prevention.
Ulcerative Cutaneous Lesions Synchronously Present with the Diagnosis of Primary Lung Cancer
Authors: Shaheen Khaldoon , Alraiyes Abdul Hamid , Baibars Motaz , Paintsil Ama , Alraies M. Chadi
Published: March 2013

The percentage of patients with lung cancer that develop skin metastases is low. The diagnosis is usually made using clinical information and skin biopsy in patients with suspicious skin lesions and history of smoking or lung cancer. The prognosis for patients having lung cancer with skin metastasis is very poor. We describe findings in a 70-year-old man with lung cancer with skin metastases. Interestingly, multiple skin lesions were the first manifestation of the underlying lung cancer. The prognosis for patients having lung cancer with skin metastasis is thus very poor.
Chitosan/Carboxymethylcellulose/Ionic Liquid/Ag(0) Nanoparticles Form a Membrane with Antimicrobial Activity
Authors: Quadros Camila , Faria Vinícius W. , Klein Manuela P. , Hertz Plinho F. , Scheeren Carla W.
Published: March 2013

Silver metal nanoparticles were immobilized in chitosan/carboxymethylcellulose/BMI.BF4(1-n-butyl-3-methylimidazolium tetrafluoroborate ionic liquid) (CS/CMC/IL) to form polymeric membrane with 20 μm thickness. The CS/CMC/IL polymeric membrane was prepared using a simple solution blending method. Irregularly shaped Ag(0) nanoparticles with monomodal size distributions of8.0±0.4 nm Ag(0) were immobilized in the membrane. The presence of small Ag(0) nanoparticles induced an augmentation in the CS/CMC/IL film surface areas. The CS/CMC/IL membrane containing Ag(0) showed increase antimicrobial activity the Ag(0) concentration increased up to saturation at 10 mg. CS/CMC/IL membrane that contains Ag(0) nanoparticles has enhanced durability of the membrane and exhibited stronger antimicrobial activity againstEscherichia coliandStaphylococcus aureus.
Approximations for Large Deflection of a Cantilever Beam under a Terminal Follower Force and Nonlinear Pendulum
Authors: Vázquez-Leal H. , Khan Y. , Herrera-May A. L. , Filobello-Nino U. , Sarmiento-Reyes A. , Jiménez-Fernández V. M. , Pereyra-Díaz D. , Perez-Sesma A. , Castaneda-Sheissa R. , Díaz-Sanchez A. , Huerta-Chua J.
Published: March 2013

In theoretical mechanics field, solution methods for nonlinear differential equations are very important because many problems are modelled using such equations. In particular, large deflection of a cantilever beam under a terminal follower force and nonlinear pendulum problem can be described by the same nonlinear differential equation. Therefore, in this work, we propose some approximate solutions for both problems using nonlinearities distribution homotopy perturbation method, homotopy perturbation method, and combinations with Laplace-Padé posttreatment. We will show the high accuracy of the proposed cantilever solutions, which are in good agreement with other reported solutions. Finally, for the pendulum case, the proposed approximation was useful to predict, accurately, the period for an angle up to179.99999999∘yielding a relative error of 0.01222747.
Systematic Design Methodology of a Wideband Multibit Continuous-Time Delta-Sigma Modulator
Authors: Anand Awinash , Koirala Nischal , Pokharel Ramesh K. , Kanaya Haruichi , Yoshida Keiji
Published: March 2013

Systematic design of a low power, wideband and multi-bit continuous-time delta-sigma modulator (CTDSM) is presented. The design methodology is illustrated with a 640 MS/s, 20 MHz signal bandwidth 4th order 2-bit CTDMS implemented in 0.18 µm CMOS technology. The implemented design achieves a peak SNDR of 65.7 dB and a high dynamic range of 70 dB while consuming only 19.7 mW from 1.8 V supply. The design achieves a FoM of 0.31 pJ/conv. Direct path compensation is employed for one clock excess loop delay compensation. In the feedforward topology, capacitive summation using the last opamp eliminates extra summation opamp.
Effects of Binary Chemical Reaction and Activation Energy on MHD Boundary Layer Heat and Mass Transfer Flow with Viscous Dissipation and Heat Generation/Absorption
Authors: Maleque Kh. Abdul
Published: March 2013

We study an unsteady MHD free convection heat and mass transfer boundary layer incompressible fluid flow past a vertical porous plate in the presence of viscous dissipation, heat generation/absorption, chemical reaction, and Arrhenius activation energy. The plate is moving with uniform velocity. The chemical reaction rate in the function of temperature is also considered. The governing partial differential equations are reduced to ordinary differential equations by introducing local similarity transformation (Maleque (2010)) and then are solved numerically by shooting method using the Nachtsheim-Swigert iteration technique. The results of the numerical solution are then presented graphically as well as the tabular form for difference values of the various parameters.
Triggers and Effectors of Oxidative Stress at Blood-Brain Barrier Level: Relevance for Brain Ageing and Neurodegeneration
Authors: Enciu Ana-Maria , Gherghiceanu Mihaela , Popescu Bogdan O.
Published: March 2013

As fundamental research advances, it is becoming increasingly clear that a clinically expressed disease implies a mixture of intertwining molecular disturbances. Oxidative stress is one of such pathogenic pathways involved in virtually all central nervous system pathologies, infectious, inflammatory, or degenerative in nature. Since brain homeostasis largely depends on integrity of blood-brain barrier (BBB), many studies focused lately on BBB alteration in a wide spectrum of brain diseases. The proper two-way molecular transfer through BBB depends on several factors, including the functional status of its tight junction (TJ) complexes of proteins sealing neighbour endothelial cells. Although there is abundant experimental work showing that oxidative stress associates BBB permeability alteration, less is known about its implications, at molecular level, in TJ protein expression or TJ-related cell signalling. In this paper, oxidative stress is presented as a common pathway for different brain pathogenic mechanisms which lead to BBB dysregulation. We revise here oxidative-induced molecular mechanisms of BBB disruption and TJ protein expression alteration, in relation to ageing and neurodegeneration.
Role of Carbamazepine in the Symptomatic Treatment of Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature
Authors: Ravikumar Sandhya , Crawford John Ross
Published: March 2013

We describe the clinical presentation and clinical course of subacute sclerosing panencephalitis in a 13-year-old previously healthy boy who recently immigrated to the United States from Iraq. He presented with macular retinopathy, followed by progressive myoclonus and encephalopathy. After extensive workup, a diagnosis of subacute sclerosing panencephalitis was suspected by the presence of period epileptiform discharges on electroencephalogram and confirmed by elevated measles titers in the cerebrospinal fluid. Combination immunomodulatory therapy with isoprinosine, ribavirin, and intra-Ommaya interferon alpha did not result in clinical improvement. Within days following the administration of carbamazepine, there was remarkable improvement in the myoclonus and he was able to ambulate independently for a period of 4 months at which time he unfortunately progressed to a vegetative state. This case highlights the importance of carbamazepine as a potential first line symptomatic treatment of subacute sclerosing panencephalitis and provides a review of the literature on the subject.
3D FE Analysis of an Embankment Construction on GRSC and Proposal of a Design Method
Authors: Tandel Yogendra K. , Solanki Chandresh H. , Desai Atul K.
Published: March 2013

Stone column is often employed for strengthening of an embankment seated on deep soft clay. But in very soft clay having undrained shear strength less than or equal to 15 kPa, stone column may not derive adequate load carrying capacity and undergo large lateral deformation due to inadequate lateral confinement. In such circumstances, reinforcement to individual stone column by geosynthetics enhances load carrying capacity and reduces lateral deformation. This paper addresses parametric study on behaviour of embankment resting on Geosynthetic Reinforced Stone Column (GRSC) considering parameters such as stone column spacing to diameter ratio, deformation modulus of stone column material, geosynthetic stiffness, thickness of soft clay, and height of embankment by 3D numerical analysis. Finally, equation for Settlement Improvement Factor (SIF), defined as ratio between settlement of embankment without treatment and with geosynthetic reinforced stone column, is proposed that correlates with the major influence parameters such as stone column spacing to diameter ratio, deformation modulus of soft clay, and geosynthetic stiffness.
Investigating the Source of Planck-Detected AME: High-Resolution Observations at 15 GHz
Authors: Perrott Yvette C. , Scaife Anna M. M. , Hurley-Walker Natasha , Grainge Keith J. B.
Published: March 2013

ThePlanck28.5 GHz maps were searched for potential Anomalous Microwave Emission (AME) regions on the scale of~3° or smaller, and several new regions of interest were selected. Ancillary data at both lower and higher frequencies were used to construct spectral energy distributions (SEDs), which seem to confirm an excess consistent with spinning dust models. Here we present higher resolution observations of two of these new regions with the Arcminute Microkelvin Imager Small Array (AMI SA) between 14 and 18 GHz to test for the presence of a compact (~10 arcmin or smaller) component. For AME-G107.1+5.2, dominated by the Hii region S140, we find evidence for the characteristic rising spectrum associated with either the spinning dust mechanism for AME or an ultra- /hypercompact Hii region across the AMI frequency band; however, for AME-G173.6+208 we find no evidence for AME on scales of~2–10 arcmin.
Curing Pressure Influence of Out-of-Autoclave Processing on Structural Composites for Commercial Aviation
Authors: Drakonakis Vasileios M. , Seferis James C. , Doumanidis Charalambos C.
Published: March 2013

Autoclaving is a process that ensures the highest quality of carbon fiber reinforced polymer (CFRP) composite structures used in aviation. During the autoclave process, consolidation of prepreg laminas through simultaneous elevated pressure and temperature results in a uniform high-end material system. This work focuses on analyzing in a fundamental way the applications of pressure and temperature separately during prepreg consolidation. A controlled pressure vessel (press-clave) has been designed that applies pressure during the curing process while the temperature is being applied locally by heat blankets. This vessel gives the ability to design manufacturing processes with different pressures while applying temperature at desired regions of the composite. The pressure role on the curing extent and its effect on the interlayer region are also tested in order to evaluate the consolidation of prepregs to a completely uniform material. Such studies may also be used to provide insight into the morphology of interlayer reinforcement concepts, which are widely used in the featherweight composites. Specimens manufactured by press-clave, which separates pressure from heat, are analytically tested and compared to autoclaved specimens in order to demonstrate the suitability of the press-clave to manufacture high-quality composites with excessively reduced cost.
Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers
Authors: Salmaso Stefano , Caliceti Paolo
Published: March 2013

Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.
On a Five-Dimensional Chaotic System Arising from Double-Diffusive Convection in a Fluid Layer
Authors: Idris R. , Siri Z. , Hashim I.
Published: March 2013

A chaotic system arising from double-diffusive convection in a fluid layer is investigated in this paper based on the theory of dynamical systems. A five-dimensional model of chaotic system is obtained using the Galerkin truncated approximation. The results showed that the transition from steady convection to chaos via a Hopf bifurcation produced a limit cycle which may be associated with a homoclinic explosion at a slightly subcritical value of the Rayleigh number.
A Methanol Extract ofBrugmansia arboreaAffects the Reinforcing and Motor Effects of Morphine and Cocaine in Mice
Authors: Bracci Antonio , Daza-Losada Manuel , Aguilar Maria , De Feo Vincenzo , Miñarro José , Rodríguez-Arias Marta
Published: March 2013

Previous reports have shown that several of the effects of morphine, including the development of tolerance and physical withdrawal symptoms, are reduced by extracts ofBrugmansia arborea(L.) Lagerheim (Solanaceae) (B. arborea). In the present study we evaluate the action of the methanol extract ofB. arborea(7.5–60 mg/kg) on the motor and reinforcing effects of morphine (20 and 40 mg/kg) and cocaine (25 mg/kg) using the conditioned place preference (CPP) procedure. At the doses employed,B. arboreadid not affect motor activity or induce any effect on CPP. The extract partially counteracted morphine-induced motor activity and completely blocked the CPP induced by 20 mg/kg morphine. On the other hand,B. arboreablocked cocaine-induced hyperactivity but did not block cocaine-induced CPP. Reinstatement of extinguished preference with a priming dose of morphine or cocaine was also inhibited byB. arborea. The complex mechanism of action ofB. arborea, which affects the dopaminergic and the cholinergic systems, seems to provide a neurobiological substrate for the effects observed. Considered as a whole, these results point toB. arboreaas a useful tool for the treatment of morphine or cocaine abuse.
Recent Progress and Future Challenges in MR Electric Properties Tomography
Authors: Katscher Ulrich , Kim Dong-Hyun , Seo Jin Keun
Published: March 2013

MR Electric Properties Tomography (EPT) is a lately developed medical imaging modality capable of visualizing both conductivity and permittivity of the patient at the Larmor frequency usingB1maps. The paper discusses the development of EPT reconstructions, EPT sequences, EPT experiments, and challenging issues of EPT.
Evaluating the Lifetime Performance Index Based on the Bayesian Estimation for the Rayleigh Lifetime Products with the Upper Record Values
Authors: Lee Wen-Chuan , Wu Jong-Wuu , Hong Ching-Wen , Hong Shie-Fan
Published: March 2013

Quality management is very important for many manufacturing industries. Process capability analysis has been widely applied in the field of quality control to monitor the performance of industrial processes. Hence, the lifetime performance indexCLis utilized to measure the performance of product, whereLis the lower specification limit. This study constructs a Bayesian estimator ofCLunder a Rayleigh distribution with the upper record values. The Bayesian estimations are based on squared-error loss function, linear exponential loss function, and general entropy loss function, respectively. Further, the Bayesian estimators ofCLare utilized to construct the testing procedure forCLbased on a credible interval in the condition of knownL. The proposed testing procedure not only can handle nonnormal lifetime data, but also can handle the upper record values. Moreover, the managers can employ the testing procedure to determine whether the lifetime performance of the Rayleigh products adheres to the required level. The hypothesis testing procedure is a quality performance assessment system in enterprise resource planning (ERP).
A High Order Theory for Linear Thermoelastic Shells: Comparison with Classical Theories
Authors: Zozulya V. V.
Published: March 2013

A high order theory for linear thermoelasticity and heat conductivity of shells has been developed. The proposed theory is based on expansion of the 3-D equations of theory of thermoelasticity and heat conductivity into Fourier series in terms of Legendre polynomials. The first physical quantities that describe thermodynamic state have been expanded into Fourier series in terms of Legendre polynomials with respect to a thickness coordinate. Thereby all equations of elasticity and heat conductivity including generalized Hooke's and Fourier's laws have been transformed to the corresponding equations for coefficients of the polynomial expansion. Then in the same way as in the 3D theories system of differential equations in terms of displacements and boundary conditions for Fourier coefficients has been obtained. First approximation theory is considered in more detail. The obtained equations for the first approximation theory are compared with the corresponding equations for Timoshenko's and Kirchhoff-Love's theories. Special case of plates and cylindrical shell is also considered, and corresponding equations in displacements are presented.
Self-Consistent Sources and Conservation Laws for Nonlinear Integrable Couplings of the Li Soliton Hierarchy
Authors: Wei Han-yu , Xia Tie-cheng
Published: March 2013

New explicit Lie algebras are introduced for which the nonlinear integrable couplings of the Li soliton hierarchy are obtained. Then, the nonlinear integrable couplings of Li soliton hierarchy with self-consistent sources are established. Finally, we present the infinitely many conservation laws for the nonlinear integrable coupling of Li soliton hierarchy.
Adsorption of Cu (II) on the Surface of Nonconventional Biomass: A Study on Forced Convective Mass Transfer in Packed Bed Column
Authors: Mishra Vishal , Balomajumder Chandrajit , Agarwal Vijay Kumar
Published: March 2013

The present investigation has dealt with the adsorption of Cu (II) across liquid phase on the nonconventional adsorbent. The nonconventional adsorbent used in the present work was Cedrus deodara sawdust obtained from local carpenter's shop. The maximum uptake capacities of Copper (II) ions at saturation and breakthrough point were 55.63 mg/g and 53.18 mg/g for an initial concentration of 93 mg/L of copper, respectively. The fitting of the experimental data in Langmuir, Freundlich, and Temkin isotherm models indicated the suitability of Langmuir isotherm in terms of very low statistical error functions that is, χ2 and sum of square errors (SSE) and higher values of (R2) linear regression coefficient. The goodness of fit of the breakthrough curve in Bohardt-Adams, Wolborska, Modified dose response, and Thomas model indicated the suitability of Thomas model with higher linear regression coefficient and lower values of statistical error functions. The flow rate and bed height affected the hydrodynamic parameters of the packed bed reactor significantly.
Synthesis and Biological Activity of 2,5‐Bisubstituted Derivatives of 1,3,4‐Thiadiazol‐2,5‐dithiol
Authors: Zhivotova T. S. , Bakirova R. E. , Fazylov S. D. , Kabieva S. K. , Kryazheva T. V.
Published: March 2013

By reaction of 1,3,4‐thiadiazol‐2,5‐dithiol with different organohalogens, chlorides of carboxylic acids, acrylic acid derivatives, alkaloids, and secondary amines, various derivatives of 2,5‐bi‐substituted 1,3,4‐thiadiazole were synthesized, and biological properties of some of them were studied.
Observer-Based Robust Control for Hydraulic Velocity Control System
Authors: Shen Wei , Jiang Jihai , Karimi Hamid Reza , Su Xiaoyu
Published: March 2013

This paper investigates the problems of robust stabilization and robust control for the secondary component speed control system with parameters uncertainty and load disturbance. The aim is to enhance the control performance of hydraulic system based on Common Pressure Rail (CPR). Firstly, a mathematical model is presented to describe the hydraulic control system. Then a novel observer is proposed, and an observed-based control strategy is designed such that the closed-loop system is asymptotically stable and satisfies the disturbance attenuation level. The condition for the existence of the developed controller can by efficiently solved by using the MATLAB software. Finally, simulation results are provided to demonstrate the effectiveness of the proposed method.
Multifunctional Logic Gate by Means of Nanodot Array with Different Arrangements
Authors: Takahashi Yasuo , Ueno Shinichiro , Arita Masashi
Published: March 2013

Multifunctional logic gate devices consisting of a nanodot array are studied from the viewpoint of single electronics. In a nanodot array, the dots come in a random variety of sizes, which sometimes has a negative effect on the performance of electrical device applications. Here, this feature is used in a positive sense to achieve higher functionality in the form of flexible logic gates with low power consumption in which the variability of logic functions is guaranteed. Nanodot arrays with two input gates and one control gate in a variety of arrangements are considered, in which the two‐input logic functions (such as NAND, NOR, or exclusive‐OR (XOR) gates) are selected by changing the voltage applied to the control gate. To ensure the flexibility of the device, it is important to guarantee the performance with any one of the six important logic functions: NAND, AND, NOR, OR, XOR, and XNOR. We ran a selection simulation using a nanodot array consisting of six nanodots with different dot arrangements to clarify the relation between the variability of the logic functions and the dot arrangements.
Tumor Inhibition by DepoVax-Based Cancer Vaccine Is Accompanied by Reduced Regulatory/Suppressor Cell Proliferation and Tumor Infiltration
Authors: Karkada Mohan , Quinton Tara , Blackman Rachelle , Mansour Marc
Published: March 2013

A successful cancer vaccine needs to overcome the effects of immune-suppressor cells such as Treg lymphocytes, suppressive cytokine-secreting Tr1 cells, and myeloid-derived suppressor cells (MDSCs), while enhancing tumor-specific immune responses. Given the relative poor efficacy associated with current cancer vaccines, a novel vaccine platform called DepoVaxTM
(DPX) was developed. C3 tumor-challenged mice were immunized with HPV-E7 peptide in DPX- or conventional-emulsion- (CE-) based vaccine. While control mice showed marked increase in Treg/MDSCs in spleen and blood, in mice treated with DPX-E7 the levels remained similar to tumor-free naive mice. Such differences were also seen within the tumor. Antigen-specific IL10-secreting CD4/CD8 T cells and TGF-β+CD8+ T cell frequencies were increased significantly in CE-treated and control mice in contrast to DPX-E7-immunized mice. Analysis of tumor-infiltrating cells revealed higher frequency of suppressor cells in untreated controls than in DPX-E7 group while the converse was true for tumor-infiltrating CD8 T cells. Immunization of tumor-bearing HLA-A2 transgenic mice with human vaccine DPX-0907, a peptide-based vaccine for breast/ovarian/prostate cancers, showed efficient induction of immune response to cancer peptides despite the presence of suppressor cells. Thus, this study provides the rationale for using DPX-based cancer vaccines in immune-suppressed cancer patients, to induce effective anticancer immunity.
The Extract of Herbal Medicines Activates AMP-Activated Protein Kinase in Diet-Induced Obese Rats
Authors: Shin Hye-Yeon , Chung SaeYeon , Kim Soon Re , Lee Ji-Hye , Seo Hye-Sook , Shin Yong-Cheol , Ko Seong-Gyu
Published: March 2013

Our study investigated whether the extract of six herbal medicines (OB-1) has an inhibitory effect on obesity. High-fat diet-(HFD-) induced rats and controls were treated with 40 mg/100 g body weight of OB-1 or saline once a day for 5 weeks. After significant changes in body weight were induced, OB-1 and saline were administered to each subgroup of HFD and control groups for additional 5 weeks. No statistically significant decrease of body weight in OB-1-treated rats was found compared to controls. However, OB-1-treated rats were found to be more active in an open-field test and have a reduction in the size of adipocytes compared to controls. We observed no changes in the mRNA expressions of leptin and adiponectin from adipocytes between OB-1- and saline-treated rats with HFD-induced obesity group. However, OB-1 treatments were shown to be inversely correlated with accumulation of lipid droplets in liver tissue, suggesting that OB-1 could inhibit a lipid accumulation by blocking the pathway related to lipid metabolism. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) was significantly increased in OB-1-treated rats with HFD compared to controls. These results suggest that OB-1 has no direct antiobesity effect and, however, could be a regulator of cellular metabolism.
Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells
Authors: Oh Jueun , Kim Ji Hye , Park Jae Gwang , Yi Young-Su , Park Kye Won , Rho Ho Sik , Lee Min-Seuk , Yoo Jae Won , Kang Seung-Hyun , Hong Yong Deog , Shin Song Seok , Cho Jae Youl
Published: March 2013

Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic, antiangiogenic, photoprotective, hepatoprotective, and neuroprotective properties. Although the anti-inflammatory effects of lutein have previously been described, the mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, in the present study, we aimed to investigate the regulatory activity of lutein in the inflammatory responses of skin-derived keratinocytes or macrophages and to elucidate the mechanism of its inhibitory action. Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL-) 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX-) 2 from interferon-γ/tumor necrosis-factor-(TNF-)α-treated HaCaT cells, and the enhancement of matrix-metallopeptidase-(MMP-) 9 level in UV-irradiated keratinocytes. By evaluating the intracellular signaling pathway and the nuclear transcription factor levels, we determined that lutein inhibited the activation of redox-sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal kinase (JNK). Evaluation of the radical and ROS scavenging activities further revealed that lutein was able to act as a strong anti-oxidant. Taken together, our findings strongly suggest that lutein-mediated AP-1 suppression and anti-inflammatory activity are the result of its strong antioxidative and p38/JNK inhibitory activities. These findings can be applied for the preparation of anti-inflammatory and cosmetic remedies for inflammatory diseases of the skin.
Fructus MumeFormula in the Treatment of Type 2 Diabetes Mellitus: A Randomized Controlled Pilot Trial
Authors: Tu Xiang , Xie ChunGuang , Wang Fei , Chen Qiu , Zuo ZhiHuang , Zhang Qiong , Wang XingShuan , Zhong Sen , Jordan James B.
Published: March 2013

Background. “Fructus Mumeor Dark Plum” (pilule form) has been used for many years in Traditional Chinese Medicine (TCM) and may be a valid treatment for type 2 diabetes mellitus (T2DM).Aim. One aspect toward efficacy validation is the evaluation of the blood glucose-lowering effect ofFructus Mume(FM) with T2DM patients in a randomized controlled trial (RCT).Methods. This pilot study uses a RCT procedure to assess efficacy ofFMand Metformin. The trial was for 12 weeks, with 80 T2DM subjects. Both groups were standardized in their diet and exercise routine. Comparisons of several variables were analyzed.Results. No significant differences were found between groups in the fasting and postprandial glucose levels although both had significant decreases. The values of glycosylated hemoglobin were significantly reduced in both groups. For patients whose body mass index (BMI) was <23, neitherFMnor Metformin had an effect on BMI; for those with a BMI between 23 and 25 or the BMI was >25, bothFMand Metformin significantly reduce the BMI.Conclusions. In this pilot study, it was demonstrated thatFructus Mumeformula may reduce the levels of blood glucose in patients with type 2 diabetes.
Comparison of Soft Tissue Cephalometric Norms between Turkish and European‐American Adults
Authors: Celebi Ahmet Arif , Tan Enes , Gelgor Ibrahim Erhan , Colak Tugba , Ayyildiz Erdem
Published: March 2013

One of the most important components of orthodontic diagnosis and treatment planning is the evaluation of the patient’s soft tissue profile. The main purpose of this study was to develop soft‐tissue cephalometric standards for Turkish men and women and compare them with the cephalometric standards of normal European‐American white people. The sample included 96 Turkish adults (48 women, 48 men), aged 20 to 27 years. Turkish subjects have increased facial convexity associated with retruded mandible, more obtuse lower face‐throat angle, increased nasolabial angle and upper lip protrusion, deeper mentolabial sulcus, and smaller interlabial gap compared with European‐American white people. It is appropriate to consider these differences during routine diagnosis and treatment planning of a Turkish patient or an American patient of European ancestry. Turkish males reveal more obtuse mandibular prognathism and upper lip protrusion, and smaller nasolabial angle than females.
Area Optimized FPGA-Based Implementation of The Sobel Compass Edge Detector
Authors: Singh Sanjay , Saini Anil Kumar , Saini Ravi , Mandal A. S. , Shekhar Chandra , Vohra Anil
Published: March 2013

This paper presents a new FPGA resource optimized hardware architecture for real-time edge detection using the Sobel compass operator. The architecture uses a single processing element to compute the gradient for all directions. This greatly economizes on the FPGA resources' usages (more than 40% reduction) while maintaining real-time video frame rates. The measured performance of the architecture is 50 fps for standard PAL size video and 200 fps for CIF size video. The use of pipelining further improved the performance (185 fps for PAL size video and 740 fps for CIF size video) without significant increase in FPGA resources.
Degradation in Seawater of Structural Adhesives for Hybrid Fibre-Metal Laminated Materials
Authors: Alia Cristina , Biezma María V. , Pinilla Paz , Arenas José M. , Suárez Juan C.
Published: March 2013

The adhesives used for applications in marine environments are subject to particular chemical conditions, which are mainly characterised by an elevated chlorine ion content and intermittent wetting/drying cycles, among others. These conditions can limit the use of adhesives due to the degradation processes that they experience. In this work, the chemical degradation of two different polymers, polyurethane and vinylester, was studied in natural seawater under immersion for different periods of time. The diffusion coefficients and concentration profiles of water throughout the thickness of the adhesives were obtained. Microstructural changes in the polymer due to the action of water were observed by SEM, and the chemical degradation of the polymer was monitored with the Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The degradation of the mechanical properties of the adhesive was determined by creep tests with Mixed Cantilever Beam (MCB) specimens at different temperatures. After 180 days of immersion of the specimens, it was concluded that theJ-integral value (depending on the strain) implies a loss of stiffness of 51% and a decrease in the failure load of 59% for the adhesive tested.
Challenges in the Application of Fractional Derivative Models in Capturing Solute Transport in Porous Media: Darcy-Scale Fractional Dispersion and the Influence of Medium Properties
Authors: Zhang Yong , Papelis Charalambos , Young Michael H. , Berli Markus
Published: March 2013

Heterogeneous media consisting of segregated flow regions are fractional-order systems, where the regional-scale anomalous diffusion can be described by the fractional derivative model (FDM). The standard FDM, however, first, cannot characterize the Darcy-scale dispersion through repacked sand columns, and second, the link between medium properties and model parameters remains unknown. To fill these two knowledge gaps, this study applies a tempered fractional derivative model (TFDM) to capture bromide transport through laboratory repacked sand. Column transport experiments are conducted first, where glass beads and silica sand with different diameters are repacked individually. Late-time tails are observed in the breakthrough curves (BTC) of bromide even in relatively homogeneous glass beads. The TFDM can capture the observed subdiffusion, especially the late-time BTC with a transient declining rate. Results also show that both the size distribution of repacked sand and the magnitude of fluid velocity can affect subdiffusion. In particular, a wider sand size distribution or a smaller flow rate can enhance the subdiffusion, leading to a smaller time index and a higher truncation parameter in the TFDM. Therefore, the Darcy-scale dispersion follows the tempered stable law, and the model parameters might be related to the soil size and flow conditions.
Simulations for Mechanical Ventilation in Children: Review and Future Prospects
Authors: Flechelles Olivier , Ho Annie , Hernert Patrice , Emeriaud Guillaume , Zaglam Nesrine , Cheriet Farida , Jouvet Philippe A.
Published: March 2013

Mechanical ventilation is a very effective therapy, but with many complications. Simulators are used in many fields, including medicine, to enhance safety issues. In the intensive care unit, they are used for teaching cardiorespiratory physiology and ventilation, for testing ventilator performance, for forecasting the effect of ventilatory support, and to determine optimal ventilatory management. They are also used in research and development of clinical decision support systems (CDSSs) and explicit computerized protocols in closed loop. For all those reasons, cardiorespiratory simulators are one of the tools that help to decrease mechanical ventilation duration and complications. This paper describes the different types of simulators described in the literature for physiologic simulation and modeling of the respiratory system, including a new simulator (SimulResp), and proposes a validation process for these simulators.
Correlation between Platelet Gelsolin and Platelet Activation Level in Acute Myocardial Infarction Rats and Intervention Effect of Effective Components of Chuanxiong Rhizome and Red Peony Root
Authors: Liu Yue , Yin Huijun , Jiang Yuerong , Xue Mei , Guo Chunyu , Shi Dazhuo , Chen Keji
Published: March 2013

The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI) of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.
Angiopoietin-2: An Attractive Target for Improved Antiangiogenic Tumor Therapy
Authors: Gerald Damien , Chintharlapalli Sudhakar , Augustin Hellmut G. , Benjamin Laura E.
Published: March 2013

Anti-VEGF pathway therapies primarily target immature blood vessels in tumors. However, emerging approaches to combine with targeted therapies impacting the later stages of remodeling and vessel maturation are expected to improve clinical efficacy by expanding the target vessel population. The angiopoietin/Tie ligand/receptor system is a prototypic regulator of vessel remodeling and maturation. Angiopoietin-2 (Ang2) appears to be a particularly attractive therapeutic target. In fact, the experimental proof-of-concept showing improved efficacy when VEGF and Ang2-targeting therapies are combined has been solidly established in preclinical models, and several Ang2-targeting drugs are in clinical trials. However, rational development of these second-generation combination therapies is hampered by a limited understanding of the biological complexity that is generated from agonistic and antagonistic Ang/Tie signaling. This review discusses recent mechanistic advances in angiopoietin signaling, particularly in light of the recent study published on REGN910 and summarizes the status quo of Ang2-targeting therapies. In light of the clarified partial agonist function of Ang2, we propose that clarity on the expression profile of the angiopoietin ligands and Tie1 and Tie2 receptors in subsets of cancer vessels and cancer cells will provide clearer hypotheses for more focused rational clinical trials to exploit this seminal pathway and improve current antiangiogenic therapies. Cancer Res; 73(6); 1649–57. ©2013 AACR.
Targeting CXCR2 Enhances Chemotherapeutic Response, Inhibits Mammary Tumor Growth, Angiogenesis, and Lung Metastasis
Authors: Sharma Bhawna , Nawandar Dhananjay M. , Nannuru Kalyan C. , Varney Michelle L. , Singh Rakesh K.
Published: March 2013

Breast cancer is one of the leading causes of cancer deaths among females. Many challenges exist in the current management of advanced stage breast cancer as there are fewer recognized therapeutic strategies, often because of therapy resistance. How breast cancer cells evade chemotherapy and the underlying mechanism remains unclear. We and others have observed that malignant cells that survive initial chemo- and radiation therapy express higher levels of CXCR2 ligands, which may provide a survival benefit leading to therapy resistance. In this report, we test the hypothesis that CXCR2-dependent signaling in malignant cells may be critical for chemotherapy resistance and targeting this signaling axis may enhance the antitumor and antimetastatic activity of chemotherapeutic drugs and limit their toxicity. We used Cl66-wt, 4T1-wt, Cl66sh-CXCR2, and 4T1sh-CXCR2 cells expressing differential levels of the CXCR2 receptor to evaluate the role of targeting CXCR2 on chemotherapeutic responses. Knockdown of CXCR2 enhances paclitaxel and doxorubicin-mediated toxicity at suboptimal doses. Moreover, we observed an increase in the expression of CXCL1, a CXCR2 ligand in paclitaxel and doxorubicin-treated mammary tumor cells, which were inhibited following CXCR2 knockdown. Knockdown of CXCR2 enhanced antitumor activity of paclitaxel in an in vivo mammary tumor model. We observed significant inhibition of spontaneous lung metastases in animals bearing CXCR2 knockdown tumors and treated with paclitaxel as compared with the control group. Our data suggest the novel role of CXCR2 and its ligands in maintaining chemotherapy resistance and provide evidence that targeting CXCR2 signaling in an adjuvant setting will help circumvent chemotherapy resistance. Mol Cancer Ther; 12(5); 799–808. ©2013 AACR.
ICEAfe1, an Actively Excising Genetic Element from the Biomining Bacterium Acidithiobacillus ferrooxidans
Authors: Bustamante Paula , Covarrubias Paulo C. , Levicán Gloria , Katz Assaf , Tapia Pablo , Holmes David , Quatrini Raquel , Orellana Omar
Published: March 2013

Integrative conjugative elements (ICEs) are self-transferred mobile genetic elements that contribute to horizontal gene transfer. An ICE (ICEAfe1) was identified in the genome of Acidithiobacillus ferrooxidans ATCC 23270. Excision of the element and expression of relevant genes under normal and DNA-damaging growth conditions was analyzed. Bioinformatic tools and DNA amplification methods were used to identify and to assess the excision and expression of genes related to the mobility of the element. Both basal and mitomycin C-inducible excision as well as expression and induction of the genes for integration/excision are demonstrated, suggesting that ICEAfe1 is an actively excising SOS-regulated mobile genetic element. The presence of a complete set of genes encoding self-transfer functions that are induced in response to DNA damage caused by mitomycin C additionally suggests that this element is capable of conjugative transfer to suitable recipient strains. Transfer of ICEAfe1 may provide selective advantages to other acidophiles in this ecological niche through dissemination of gene clusters expressing transfer RNAs, CRISPRs, and exopolysaccharide biosynthesis enzymes, probably by modification of translation efficiency, resistance to bacteriophage infection and biofilm formation, respectively. These data open novel avenues of research on conjugative transformation of biotechnologically relevant microorganisms recalcitrant to genetic manipulation.