bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Synthesis, Characterisation, and Biocompatibility of Nanometre Scale Porous Anodic Aluminium Oxide Membranes for Use as a Cell Culture Substrate for the Vero Cell Line: A Preliminary Study
Authors: Poinern Gérrard Eddy Jai , Le Xuan Thi , O'Dea Mark , Becker Thomas , Fawcett Derek
Published: January 2014

In this preliminary study we investigate for the first time the biomedical potential of using porous anodic aluminium oxide (AAO) membranes as a cell substrate for culturing theCercopithecus aethiops(African green monkey) Kidney (Vero) epithelial cell line. One advantage of using the inorganic AAO membrane is the presence of nanometre scale pore channels that allow the exchange of molecules and nutrients across the membrane. The size of the pore channels can be preselected by adjusting the controlling parameters of a temperature controlled two-step anodization process. The cellular interaction and response of the Vero cell line with an in-house synthesised AAO membrane, a commercially available membrane, and a glass control were assessed by investigating cell adhesion, morphology, and proliferation over a 72 h period. The number of viable cells proliferating over the respective membrane surfaces revealed that the locally produced in-house AAO membrane had cells numbers similar to the glass control. The study revealed evidence of focal adhesion sites over the surface of the nanoporous membranes and the penetration of cellular extensions into the pore structure as well. The outcome of the study has revealed that nanometre scale porous AAO membranes have the potential to become practical cell culture scaffold substrates with the capability to enhance adhesion and proliferation of Vero cells.
Determining the First Probability Density Function of Linear Random Initial Value Problems by the Random Variable Transformation (RVT) Technique: A Comprehensive Study
Authors: Casabán M.-C. , Cortés J.-C. , Romero J.-V. , Roselló M.-D.
Published: January 2014

Deterministic differential equations are useful tools for mathematical modelling. The consideration of uncertainty into their formulation leads to random differential equations. Solving a random differential equation means computing not only its solution stochastic process but also its main statistical functions such as the expectation and standard deviation. The determination of its first probability density function provides a more complete probabilistic description of the solution stochastic process in each time instant. In this paper, one presents a comprehensive study to determinate the first probability density function to the solution of linear random initial value problems taking advantage of the so-called random variable transformation method. For the sake of clarity, the study has been split into thirteen cases depending on the way that randomness enters into the linear model. In most cases, the analysis includes the specification of the domain of the first probability density function of the solution stochastic process whose determination is a delicate issue. A strong point of the study is the presentation of a wide range of examples, at least one of each of the thirteen casuistries, where both standard and nonstandard probabilistic distributions are considered.
Effects of Density Stratification on Mixing Enhancement by Shock Wave in Supersonic Shear Layer Flows
Authors: Yun-Long Zhang , Bing Wang , Hui-Qiang Zhang , Shu-Yan Xue
Published: January 2014

We analyze the response of passive mixing to shock wave in a density-stratified supersonic shear layer by means of direct numerical simulation with a high-order hybrid compact-WENO scheme. The coexistence gradients of density and pressure have a complex influence on generation of baroclinic vorticity, depending on the gradient directions. The growth rate of mixing layer thickness is increased by the presence of shock wave, but the mixing layer thickness is not always increased. The passive mixing can be enhanced in a thickened shear layer by the incident shock wave if the homodromous vortexes are induced by the baroclinic torque. The mixing efficiency is also enhanced by increasing the density difference of two streams. The present study can be helpful to take measures to strengthen the mixing process in supersonic shear flows.
Promoter Methylation ofSFRP3Is Frequent in Hepatocellular Carcinoma
Authors: Lin Ya-Wen , Shih Yu-Lueng , Lien Gi-Shih , Suk Fat-Moon , Hsieh Chung-Bao , Yan Ming-De
Published: January 2014

Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Because there have been no reports about the role ofSFRP3in hepatocellular carcinoma (HCC), we investigated the level of methylation and transcription ofSFRP3. Four HCC cell lines, 60 HCCs, 23 cirrhosis livers, 37 chronic hepatitis livers, and 30 control livers were prescreened forSFRP3promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing.SFRP3promoter methylation was observed in 100%, 60%, 39.1%, 16.2%, and 0% in HCC cell lines, primary HCCs, cirrhosis livers, chronic hepatitis livers, and control livers, respectively. Demethylation treatment with 5-aza-2′-deoxycytidine in HCC cells restored or increased theSFRP3mRNA expression. We next used quantitative MS-PCR (QMSP) to analyze the methylation level ofSFRP3in 60 HCCs and their corresponding nontumor tissues. Methylation ofSFRP3promoter region in HCCs increased significantly compared with control tissues. There is a positive correlation between promoter hypermethylation andSFRP3mRNA downregulation. Our data suggest that promoter hypermethylation ofSFRP3is a common event in HCCs and plays an important role in regulation ofSFRP3mRNA expression.
H. pyloriVirulence Factors: Influence on Immune System and Pathology
Authors: Kalali Behnam , Mejías-Luque Raquel , Javaheri Anahita , Gerhard Markus
Published: January 2014

Helicobacter pyloriis the most widespread chronic bacterial agent in humans and is well recognized for its association with ulcer disease and gastric cancer, with both representing major global health and socioeconomic issues. Given the high level of adaptation and the coevolution of this bacterium with its human host, a thorough and multidirectional view of the specific microbiological characteristics of this infection as well as the host physiology is needed in order to develop novel means of prevention of therapy. This review aims to pinpoint some of these potentially important angles, which have to be considered mutually when studyingH. pylori’s pathogenicity. The host’s biological changes due to the virulence factors are a valuable pillar ofH. pyloriresearch as are the mechanisms by which bacteria provoke these changes. In this context, necessary adhesion molecules and significant virulence factors ofH. pyloriare discussed. Moreover, metabolism of the bacteria, one of the most important aspects for a better understanding of bacterial physiology and consequently possible therapeutic and prophylactic strategies, is addressed. On the other hand, we discuss the recent experimental proofs of the “hygiene hypothesis” in correlation withHelicobacter’s infection, which adds another aspect of complexity to this infection.
Surface Roughness Optimization of Polyamide-6/Nanoclay Nanocomposites Using Artificial Neural Network: Genetic Algorithm Approach
Authors: Moghri Mehdi , Madic Milos , Omidi Mostafa , Farahnakian Masoud
Published: January 2014

During the past decade, polymer nanocomposites attracted considerable investment in research and development worldwide. One of the key factors that affect the quality of polymer nanocomposite products in machining is surface roughness. To obtain high quality products and reduce machining costs it is very important to determine the optimal machining conditions so as to achieve enhanced machining performance. The objective of this paper is to develop a predictive model using a combined design of experiments and artificial intelligence approach for optimization of surface roughness in milling of polyamide-6 (PA-6) nanocomposites. A surface roughness predictive model was developed in terms of milling parameters (spindle speed and feed rate) and nanoclay (NC) content using artificial neural network (ANN). As the present study deals with relatively small number of data obtained from full factorial design, application of genetic algorithm (GA) for ANN training is thought to be an appropriate approach for the purpose of developing accurate and robust ANN model. In the optimization phase, a GA is considered in conjunction with the explicit nonlinear function derived from the ANN to determine the optimal milling parameters for minimization of surface roughness for each PA-6 nanocomposite.
Point of Care Technologies for HIV
Authors: Haleyur Giri Setty Mohan Kumar , Hewlett Indira K.
Published: January 2014

Effective prevention of HIV/AIDS requires early diagnosis, initiation of therapy, and regular plasma viral load monitoring of the infected individual. In addition, incidence estimation using accurate and sensitive assays is needed to facilitate HIV prevention efforts in the public health setting. Therefore, more affordable and accessible point-of-care (POC) technologies capable of providing early diagnosis, HIV viral load measurements, and CD4 counts in settings where HIV is most prevalent are needed to enable appropriate intervention strategies and ultimately stop transmission of the virus within these populations to achieve the future goal of an AIDS-free generation. This review discusses the available and emerging POC technologies for future application to these unmet public health needs.
Φ-Admissible Sublinear Singular Operators and Generalized Orlicz-Morrey Spaces
Authors: Hasanov Javanshir J.
Published: January 2014

We study the boundedness ofΦ-admissible sublinear singular operators on Orlicz-Morrey spacesMΦ,φℝn. These conditions are satisfied by most of the operators in harmonic analysis, such as the Hardy-Littlewood maximal operator and Calderón-Zygmund singular integral operator.
Neuroprotection in Stroke: Past, Present, and Future
Authors: Majid Arshad
Published: January 2014

Stroke is a devastating medical condition, killing millions of people each year and causing serious injury to many more. Despite advances in treatment, there is still little that can be done to prevent stroke-related brain damage. The concept of neuroprotection is a source of considerable interest in the search for novel therapies that have the potential to preserve brain tissue and improve overall outcome. Key points of intervention have been identified in many of the processes that are the source of damage to the brain after stroke, and numerous treatment strategies designed to exploit them have been developed. In this review, potential targets of neuroprotection in stroke are discussed, as well as the various treatments that have been targeted against them. In addition, a summary of recent progress in clinical trials of neuroprotective agents in stroke is provided.
Transforming Growth Factor-Beta and Matrix Metalloproteinases: Functional Interactions in Tumor Stroma-Infiltrating Myeloid Cells
Authors: Krstic Jelena , Santibanez Juan F.
Published: January 2014

Transforming growth factor-beta (TGF-β) is a pleiotropic factor with several different roles in health and disease. In tumorigenesis, it may act as a protumorigenic factor and have a profound impact on the regulation of the immune system response. Matrix metalloproteinases (MMPs) are a family that comprises more than 25 members, which have recently been proposed as important regulators acting in tumor stroma by regulating the response of noncellular and cellular microenvironment. Tumor stroma consists of several types of resident cells and infiltrating cells derived from bone marrow, which together play crucial roles in the promotion of tumor growth and metastasis. In cancer cells, TGF-βregulates MMPs expression, while MMPs, produced by either cancer cells or residents’ stroma cells, activate latent TGF-βin the extracellular matrix, together facilitating the enhancement of tumor progression. In this review we will focus on the compartment of myeloid stroma cells, such as tumor-associated macrophages, neutrophils, and dendritic and mast cells, which are potently regulated by TGF-βand produce large amounts of MMPs. Their interplay and mutual implications in the generation of pro-tumorigenic cancer microenvironment will be analyzed.
Membrane Properties Involved in Calcium-Stimulated Microparticle Release from the Plasma Membranes of S49 Lymphoma Cells
Authors: Campbell Lauryl E. , Nelson Jennifer , Gibbons Elizabeth , Judd Allan M. , Bell John D.
Published: January 2014

This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32–42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.
Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node
Authors: Li Xiang , Zhang Ji-qian , Shuai Jian-wei
Published: January 2014

The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+transient, andiNachanges induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase iniNaandiCa,Twhich were reduced by the mutation.
Dengue Outbreak in a Hilly State of Arunachal Pradesh in Northeast India
Authors: Khan Siraj A. , Dutta Prafulla , Topno Rashmee , Soni Monika , Mahanta Jagadish
Published: January 2014

Dengue has been reported from plains as well as hilly regions of India including some parts of Northeast India. In July-August 2012, outbreak of fever with unknown origin (FUO) indicative of Dengue was reported in Pasighat, East Siang district of Arunachal Pradesh (AP) state. Serum samples (n= 164) collected from patients from Health Training and Research Centre General Hospital, Pasighat, were tested for NS1 antigen and IgM antibodies. NS1-positive samples were analyzed by RT-PCR assay and entomological surveys were carried out. The majority of suspected cases reported NS1 antigen positivity. Females and young adults were mostly affected. The majority of the amplified NS1-positive samples showed Dengue serotype 3 infection.Aedes(Stegomyia)albopictus, known as semiurban breeding mosquitoes, was the only potential vector species identified from the affected areas of Pasighat which single handedly contributed to the outbreak. Thus, the present work identifies Dengue as an emerging arboviral infection in hilly state of AP along with a looming risk of its spread to neighbouring areas.
Integrating Energy and Environmental Management in Wood Furniture Industry
Authors: Gordić Dušan , Babić Milun , Jelić Dubravka , Konćalović Davor , Vukašinović Vladimir
Published: January 2014

As energy costs continue to rise, industrial plants (even those of energy nonintensive industries such as furniture industry) need effective way to reduce the amount of energy they consume. Besides, there are a number of economic and environmental reasons why a company should consider environmental management initiatives. This paper provides a detailed guideline for implementing joint energy and environmental management system in wood furniture industrial company. It covers in detail all essential aspects of the system: initial system assessment, organization, policy development, energy and environmental auditing, action plan development, system promotion, checking system performance, and management review.
On the Riesz Potential and Its Commutators on Generalized Orlicz-Morrey Spaces
Authors: Guliyev Vagif S. , Deringoz Fatih
Published: January 2014

We consider generalized Orlicz-Morrey spacesMΦ,φ(ℝn)including their weak versionsWMΦ,φ(ℝn). In these spaces we prove the boundedness of the Riesz potential fromMΦ,φ1(ℝn)toMΨ,φ2(ℝn)and fromMΦ,φ1(ℝn)toWMΨ,φ2(ℝn). As applications of those results, the boundedness of the commutators of the Riesz potential on generalized Orlicz-Morrey space is also obtained. In all the cases the conditions for the boundedness are given either in terms of Zygmund-type integral inequalities on(φ1,φ2), which do not assume any assumption on monotonicity ofφ1(x,r),φ2(x,r)inr.
Rapid Preparation of Biosorbents with High Ion Exchange Capacity from Rice Straw and Bagasse for Removal of Heavy Metals
Authors: Rungrodnimitchai Supitcha
Published: January 2014

This work describes the preparation of the cellulose phosphate with high ion exchange capacity from rice straw and bagasse for removal of heavy metals. In this study, rice straw and bagasse were modified by the reaction with phosphoric acid in the presence of urea. The introduced phosphoric group is an ion exchangeable site for heavy metal ions. The reaction by microwave heating yielded modified rice straw and modified bagasse with greater ion exchange capacities (∼3.62 meq/g) and shorter reaction time (1.5–5.0 min) than the phosphorylation by oil bath heating. Adsorption experiments towards Pb2+, Cd2+, and Cr3+ions of the modified rice straw and the modified bagasse were performed at room temperature (heavy metal concentration 40 ppm, adsorbent 2.0 g/L). The kinetics of adsorption agreed with the pseudo-second-order model. It was shown that the modified rice straw and the modified bagasse could adsorb heavy metal ions faster than the commercial ion exchange resin (Dowax). As a result of Pb2+sorption test, the modified rice straw (RH-NaOH 450W) removed Pb2+much faster in the initial step and reached 92% removal after 20 min, while Dowax (commercial ion exchange resin) took 90 min for the same removal efficiency.
Multivariate Statistical Analyses of Fluoride and Other Physicochemical Parameters in Groundwater Samples of Two Megacities in Asia: Lahore and Sialkot
Authors: Tariq Saadia Rashid
Published: January 2014

The present study was carried out to evaluate the current status of contaminants and their sources in groundwater samples collected from Lahore and Sialkot. A total of 93 samples were collected from different localities of Lahore and Sialkot and analyzed for the determination of various physicochemical parameters. The results of the study revealed that mean fluoride and chloride contents of water samples from Lahore were higher than the values recommended by Pak-EPA and WHO whereas the mean nitrate and sulphate levels of these samples were well within the limits. The order observed for these physicochemical parameters from Lahore was Cl−> alkalinity >SO4-2>NO3-> F−. All the observed physicochemical parameters for water samples from Sialkot were found to be greater than those of Lahore, due to a more intensive industrial activity in Sialkot. The correlation study revealed the strongest correlation among conductance and alkalinity in samples from both cities. Fluoride and sulphate were found to be positively correlated in samples from Lahore and negatively correlated in samples from Sialkot. Multivariate analysis in terms of principle component analysis and cluster analysis furnished information about the sources of various parameters in groundwater samples.
Solutions of a Quadratic Inverse Eigenvalue Problem for Damped Gyroscopic Second-Order Systems
Authors: Zhong Hong-Xiu , Chen Guo-Liang , Zhang Xiang-Yun
Published: January 2014

Givenkpairs of complex numbers and vectors (closed under conjugation), we consider the inverse quadratic eigenvalue problem of constructingn×nreal matricesM,D,G, andK, whereM>0,KandDare symmetric, andGis skew-symmetric, so that the quadratic pencilQ(λ)=λ2M+λ(D+G)+Khas the givenkpairs as eigenpairs. First, we construct a general solution to this problem withk≤n. Then, with the special propertiesD=0andK<0, we construct a particular solution. Numerical results illustrate these solutions.
Formation and Regulation of Mitochondrial Membranes
Authors: Schenkel Laila Cigana , Bakovic Marica
Published: January 2014

Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER) and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.
Palaeobiology of Silurian Leptaeninae (Brachiopoda) from Gotland, Sweden
Authors: Hoel Ole A.
Published: January 2014

Leptaenine brachiopods are common and widespread on Gotland. Lepidoleptaena poulseni and Leptaena rhomboidalis retained a functional apical pedicle throughout ontogeny, and both had strong adductor muscles and robust ornamentation, allowing them to occupy shallow water and high energy environments. A pedicle-shortening muscle is present within the pedicle tube of Leptaena rhomboidalis. Leptaena sperion, L. depressa visbyensis, and L. depressa lata inhabited low energy environments, retaining very slender pedicles. L. depressa depressa and L. parvorugata atrophied the pedicle early and then lived ambitopically in deeper water. The presence or absence of the apical pedicle strongly influenced the cardinal process morphology. Leptaenine shells had a small gape. The lophophore was simple, similar to productids and Leptaenoidea. In closed valves, the inner epithelium of leptaenine trails remained exposed to the sea. This was probably important in gas exchange. The life position of pedically attached species was with the disc vertical. Some ambitopic specimens may have retained a similar attitude. Shells of L. depressa depressa and Lepidoleptaena poulseni commonly are encrusted by epibionts, apparently without problems for larger shells. Small shells are shown to have been killed by bryozoan epizoans. Repaired shell damage is rare on the disc but is common along the commisure.
Self‐Similarity Superresolution for Resource‐Constrained Image Sensor Node in Wireless Sensor Networks
Authors: Wang Yuehai , Wang Weidong , Cao Shiying , Li Shiju , Xie Li , Ding Baocang
Published: January 2014

Wireless sensor networks, in combination with image sensors, open up a grand sensing application field. It is a challenging problem to recover a high resolution (HR) image from its low resolution (LR) counterpart, especially for low‐cost resource‐constrained image sensors with limited resolution. Sparse representation‐based techniques have been developed recently and increasingly to solve this ill‐posed inverse problem. Most of these solutions are based on an external dictionary learned from huge image gallery, consequently needing tremendous iteration and long time to match. In this paper, we explore the self‐similarity inside the image itself, and propose a new combined self‐similarity superresolution (SR) solution, with low computation cost and high recover performance. In the self‐similarity image super resolution model (SSIR), a small size sparse dictionary is learned from the image itself by the methods such as KSVD. The most similar patch is searched and specially combined during the sparse regulation iteration. Detailed information, such as edge sharpness, is preserved more faithfully and clearly. Experiment results confirm the effectiveness and efficiency of this double self‐learning method in the image super resolution.
Radiation-Enhancement Properties of an X-Band Woodpile EBG and Its Application to a Planar Antenna
Authors: Frezza Fabrizio , Pajewski Lara , Piuzzi Emanuele , Ponti Cristina , Schettini Giuseppe
Published: January 2014

A woodpile Electromagnetic Bandgap (EBG) material has been designed, by using an in-house code that implements the Fourier Modal Method (FMM). A couple of alumina-woodpile samples have been fabricated. Several results have been collected for the transmission behaviour of the woodpile and of resonators with woodpile mirrors, in a shielded anechoic chamber, by using a vector network analyzer, in the 8–12 GHz range. These new experimental data highlight interesting properties of 3D EBG resonators and suggest possible innovative applications. Comparisons of the collected results with FMM show a satisfactory agreement. An application of the EBG resonator has been considered, for gain enhancement of a microstrip antenna: an increase of about 10 dB in the broadside gain has been measured; experimental data and numerical results obtained with the commercial software HFSS show a good agreement. A comparison is presented between EBG resonator antennas and two-dimensional uniform arrays. Finally, HFSS results are provided for EBG resonator antennas working at higher frequencies or with a more selective superstrate: a gain enhancement of more than 18 dB is achieved by such antennas.
Stresses and Disability in Depression across Gender
Authors: Deshpande Sharmishtha S. , Kalmegh Bhalchandra , Patil Poonam N. , Ghate Madhav R. , Sarmukaddam Sanjeev , Paralikar Vasudeo P.
Published: January 2014

Depression, though generally episodic, results in lasting disability, distress, and burden. Rising prevalence of depression and suicide in the context of epidemiological transition demands more attention to social dimensions like gender related stresses, dysfunction, and their role in outcome of depression. Cross-sectional and follow-up assessment of men and women with depression at a psychiatric tertiary centre was undertaken to compare their illness characteristics including suicidal ideation, stresses, and functioning on GAF, SOFAS, and GARF scales (N=107). We reassessed the patients on HDRS-17 after 6 weeks of treatment. Pairedt-test and chi-square test of significance were used to compare the two groups, both before and after treatment. Interpersonal and marital stresses were reported more commonly by women (P<0.001) and financial stresses by men (P<0.001) though relational functioning was equally impaired in both. Women had suffered stresses for significantly longer duration (P=0.0038). Men had more impairment in social and occupational functioning compared to females (P=0.0062). History of suicide attempts was significantly associated with more severe depression and lower levels of functioning in case of females with untreated depression. Significant cross-gender differences in stresses, their duration, and types of dysfunction mandate focusing on these aspects over and above the criterion-based diagnosis.
Note on the Convergence Analysis of Homotopy Perturbation Method for Fractional Partial Differential Equations
Authors: Elbeleze Asma Ali , Kılıçman Adem , Taib Bachok M.
Published: January 2014

We apply the homotopy perturbation method to obtain the solution of partial differential equations of fractional order. This method is powerful tool to find exact and approximate solution of many linear and nonlinear partial differential equations of fractional order. Convergence of the method is proved and the convergence analysis is reliable enough to estimate the maximum absolute truncated error of the series solution. The fractional derivatives are described in the Caputo sense. Some examples are presented to verify convergence hypothesis and simplicity of the method.
Immediate Care of Open Extremity Fractures: Where Can We Improve?
Authors: Walton R. , Manara J. , Elamin S. E. , Braithwaite I. , Wood E.
Published: January 2014

Clear guidelines are set by the British Orthopaedic Association (BOA) and British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) on the preoperative management of open fractures. This as well as the clinical consequences of poor management of open fractures means the patient workup for surgery is important as well as the timing of surgery. Experience suggests few patients are managed 100% as per the guidelines and we look to test this hypothesis. A retrospective analysis was undertaken of all open long bone fractures (total 133), excluding hand injuries, which presented to a district general hospital over a 5-year period. The implementation of 7 defined key tasks for initial management was recorded. 101 cases were eligible, with the majority of cases (71.4%) having initial orthopaedic assessment outside normal working hours. The mean number of tasks completed was 3.23/7. Assessment out of hours was associated with less tasks being implemented but doctor seniority and the presence of polytrauma made no difference to the quality of acute care. Staff involved in the acute care of open fractures require targeted education to improve the delivery of initial preoperative care. We recommend that other centres assess their performance against this data.
Carbon Nanotubes Hybrid Hydrogels in Drug Delivery: A Perspective Review
Authors: Cirillo Giuseppe , Hampel Silke , Spizzirri Umile Gianfranco , Parisi Ortensia Ilaria , Picci Nevio , Iemma Francesca
Published: January 2014

The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review.
Kinetic-Monte-Carlo-Based Parallel Evolution Simulation Algorithm of Dust Particles
Authors: Hu Xiaomei , Xu Zhifeng , Cai Hongxia , Hu Junjun
Published: January 2014

The evolution simulation of dust particles provides an important way to analyze the impact of dust on the environment. KMC-based parallel algorithm is proposed to simulate the evolution of dust particles. In the parallel evolution simulation algorithm of dust particles, data distribution way and communication optimizing strategy are raised to balance the load of every process and reduce the communication expense among processes. The experimental results show that the simulation of diffusion, sediment, and resuspension of dust particles in virtual campus is realized and the simulation time is shortened by parallel algorithm, which makes up for the shortage of serial computing and makes the simulation of large-scale virtual environment possible.
Protective Effect of Alpha-Tocopherol Isomer from Vitamin E against the H2O2Induced Toxicity on Dental Pulp Cells
Authors: Vargas Fernanda da Silveira , Soares Diana Gabriela , Ribeiro Ana Paula Dias , Hebling Josimeri , De Souza Costa Carlos Alberto
Published: January 2014

The aim of this study was to evaluate the protective effects of different concentrations of vitamin E alpha-tocopherol (α-T) isomer against the toxicity of hydrogen peroxide (H2O2) on dental pulp cells. The cells (MDPC-23) were seeded in 96-well plates for 72 hours, followed by treatment with 1, 3, 5, or 10 mMα-T for 60 minutes. They were then exposed or not to H2O2for 30 minutes. In positive and negative control groups, the cells were exposed to culture medium with or without H2O2(0.018%), respectively. Cell viability was evaluated by MTT assay (Kruskal-Wallis and Mann-Whitney tests;α=5%). Significant reduction of cell viability (58.5%) was observed in positive control compared with the negative control. Cells pretreated withα-T at 1, 3, 5, and 10 mM concentrations and exposed to H2O2had their viability decreased by 43%, 32%, 25%, and 27.5%, respectively. These values were significantly lower than those observed in the positive control, thereby showing a protective effect ofα-T against the H2O2toxicity. Overall, the vitamin Eα-T isomer protected the immortalized MDPC-23 pulp cells against the toxic effects of H2O2. The most effective cell protection was provided by 5 and 10 mM concentrations ofα-T.
A Method for Estimation of Extreme Values of Wind Pressure on Buildings Based on the Generalized Extreme‐Value Theory
Authors: Quan Yong , Wang Fei , Gu Ming
Published: January 2014

By analysis of statistical characteristics and probability density distribution of extreme values of wind pressures on the surfaces of a typical low‐rise building model and a typical high‐rise building model, characteristics of the commonly used methods for estimating the extreme‐values of wind pressure are discussed. The relationship between the parameters of the extreme value distribution of wind pressure and its observation length is then deduced based on the generalized extreme value theory and the independence of the observed extreme values. A new method for estimating the extreme values is developed by dividing the time history sample of the wind pressure into several subsamples. The extreme values of the wind pressure coefficients calculated with the present method and those with the commonly used methods are compared and the results indicate that the present method can estimate the extreme values of non‐Gaussian wind pressure more accurately than the commonly used ones.
Bifurcation Analysis of an SIR Epidemic Model with the Contact Transmission Function
Authors: Li Guihua , Li Gaofeng
Published: January 2014

We consider an SIR endemic model in which the contact transmission function is related to the number of infected population. By theoretical analysis, it is shown that the model exhibits the bistability and undergoes saddle-node bifurcation, the Hopf bifurcation, and the Bogdanov-Takens bifurcation. Furthermore, we find that the threshold value of disease spreading will be increased, when the half-saturation coefficient is more than zero, which means that it is an effective intervention policy adopted for disease spreading. However, when the endemic equilibria exist, we find that the disease can be controlled as long as we let the initial values lie in the certain range by intervention policy. This will provide a theoretical basis for the prevention and control of disease.
HDAC2 Provides a Critical Support to Malignant Progression of Hepatocellular Carcinoma through Feedback Control of mTORC1 and AKT
Authors: Noh Ji Heon , Bae Hyun Jin , Eun Jung Woo , Shen Qingyu , Park Se Jin , Kim Hyung Seok , Nam Boas , Shin Woo Chan , Lee Eun Kyung , Lee Kyungbun , Jang Ja-Jun , Park Won Sang , Lee Jung Young , Nam Suk Woo
Published: January 2014

Aberrant regulation of histone deacetylase 2 (HDAC2) contributes to malignant progression in various cancers, but the underlying mechanism leading to the activation of oncogenic HDAC2 remains unknown. In this study, we show that HDAC2 expression is upregulated in a large cohort of patients with human hepatocellular carcinoma, and that high expression of HDAC2 was significantly associated with poor prognosis of patients with hepatocellular carcinoma. We found that mTORC1/NF-κBp50 signaling is necessary for the growth factor–induced HDAC2 and is sustained in hepatocellular carcinoma, but not in normal hepatic cells. Growth factor–induced mTORC1 activates the nuclear translocation of NF-κBp50, where it binds to the intragenic sequences of the HDAC2 gene and promotes its transcription. Hepatocellular carcinoma tissues derived from chemical-induced mouse and rat liver cancer models validated that mTORC1 activation and NF-κBp50 nuclear translocation are essential for the transcriptional activation of oncogenic HDAC2 in hepatocellular carcinoma. In addition, we demonstrate that HDAC2 is required to maintain mTORC1 activity by stabilizing the mTOR/RAPTOR complex. Elevated expression of HDAC2 triggers a positive feedback loop that activates AKT phosphorylation via the transcriptional modulation of phosphoinositide signaling molecules. Bioinformatics analysis of HDAC2 signature and immunoblot analysis of mesenchymal genes also evidenced that HDAC2 plays a role in the malignant behavior of tumor cells by Snail induction and simultaneously E-cadherin suppression in hepatocellular carcinoma cells. These findings establish a molecular mechanism responsible for the activation of oncogenic HDAC2, which explains how growth factor–induced HDAC2 maintains mitogenic signaling and function during hepatocellular malignant progression and provide a novel strategy for therapeutic intervention in liver cancer. Cancer Res; 74(6); 1728–38. ©2014 AACR.
MET Signaling in Colon Cancer Stem-like Cells Blunts the Therapeutic Response to EGFR Inhibitors
Authors: Luraghi Paolo , Reato Gigliola , Cipriano Elia , Sassi Francesco , Orzan Francesca , Bigatto Viola , De Bacco Francesca , Menietti Elena , Han May , Rideout William M. , Perera Timothy , Bertotti Andrea , Trusolino Livio , Comoglio Paolo M. , Boccaccio Carla
Published: January 2014

Metastatic colorectal cancer remains largely incurable, although in a subset of patients, survival is prolonged by new targeting agents such as anti-EGF receptor (anti-EGFR) antibodies. This disease is believed to be supported by a subpopulation of stem-like cells termed colon cancer–initiating cell (CCIC), which may also confer therapeutic resistance. However, how CCICs respond to EGFR inhibition has not been fully characterized. To explore this question, we systematically generated CCICs through spheroid cultures of patient-derived xenografts of metastatic colorectal cancer. These cultures, termed “xenospheres,” were capable of long-term self-propagation in vitro and phenocopied the original patient tumors in vivo, thus operationally defining CCICs. Xenosphere CCICs retained the genetic determinants for EGFR therapeutic response in vitro and in xenografts; like the original tumors, xenospheres harboring a mutated KRAS gene were resistant to EGFR therapy, whereas those harboring wild-type RAS pathway genes (RASwt) were sensitive. Notably, the effects of EGFR inhibition in sensitive CCICs could be counteracted by cytokines secreted by cancer-associated fibroblasts. In particular, we found that the MET receptor ligand hepatocyte growth factor (HGF) was especially active in supporting in vitro CCIC proliferation and resistance to EGFR inhibition. Ectopic production of human HGF in CCIC xenografts rendered the xenografts susceptible to MET inhibition, which sensitized the response to EGFR therapy. By showing that RASwt CCICs rely on both EGFR and MET signaling, our results offer a strong preclinical proof-of-concept for concurrent targeting of these two pathways in the clinical setting. Cancer Res; 74(6); 1857–69. ©2014 AACR.
TGF-β–Induced Upregulation of malat1 Promotes Bladder Cancer Metastasis by Associating with suz12
Authors: Fan Yu , Shen Bing , Tan Mingyue , Mu Xinyu , Qin Yan , Zhang Fang , Liu Yong
Published: January 2014

Purpose: TGF-β promotes tumor invasion and metastasis by inducing an epithelial–mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA malat1 (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator of the metastasis phenotype of lung cancer cells.

Experimental Design: We, therefore, investigated whether TGF-β regulates malat1 expression to promote tumor metastasis of bladder cancer. The expression levels of malat1 and EMT markers were assayed in specimens of bladder cancer. The role of malat1 in regulating bladder cancer metastasis was evaluated in cell and animal models.

Results: TGF-β induces malat1 expression and EMT in bladder cancer cells. malat1 overexpression is significantly correlated with poor survival in patients with bladder cancer. malat1 and E-cadherin expression is negatively correlated in vitro and in vivo. malat1 knockdown inhibits TGF-β–induced EMT. malat1 is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that malat1 or suz12 knockdown inhibits tumor metastasis in animal models.

Conclusion: These data suggest that malat1 is an important mediator of TGF-β–induced EMT, and suggest that malat1 inhibition may represent a promising therapeutic option for suppressing bladder cancer progression. Clin Cancer Res; 20(6); 1531–41. ©2014 AACR.
Rapid Induction of Androgen Receptor Splice Variants by Androgen Deprivation in Prostate Cancer
Authors: Yu Ziyang , Chen Sen , Sowalsky Adam G. , Voznesensky Olga S. , Mostaghel Elahe A. , Nelson Peter S. , Cai Changmeng , Balk Steven P.
Published: January 2014

Purpose: Mechanisms mediating androgen receptor (AR) reactivation in prostate cancer that progresses after castration (castration-resistant prostate cancer; CRPC) and subsequent treatment with abiraterone (CYP17A1 inhibitor that further suppresses androgen synthesis) remain unclear.

Experimental Design: Prostate cancer xenografts were examined to identify mechanism of progression after castration and abiraterone.

Results: AR reactivation in abiraterone-resistant VCaP xenografts was not associated with restoration of intratumoral androgens or alterations in AR coregulators. In contrast, mRNA encoding full-length AR (AR-FL) and a constitutively active splice variant (AR-V7) were increased compared with xenografts before castration, with an increase in AR-V7 relative to AR-FL. This shift toward AR-V7 was due to a feedback mechanism whereby the androgen-liganded AR stimulates expression of proteins that suppress generation of AR-V7 relative to AR-FL transcripts. However, despite the increases in AR-V7 mRNA, it remained a minor transcript (<1%) relative to AR-FL in resistant VCaP xenografts and CRPC clinical samples. AR-V7 protein expression was similarly low relative to AR-FL in castration-resistant VCaP xenografts and androgen-deprived VCaP cells, but the weak basal AR activity in these latter cells was further repressed by AR-V7 siRNA.

Conclusions: AR-V7 at these low levels is not adequate to restore AR activity, but its rapid induction after androgen deprivation allows tumors to retain basal AR activity that may be needed for survival until more potent mechanisms emerge to activate AR. Agents targeting AR splice variants may be most effective when used very early in conjunction with therapies targeting the AR ligand-binding domain. Clin Cancer Res; 20(6); 1590–600. ©2014 AACR.
Novel ATP-Competitive MEK Inhibitor E6201 Is Effective against Vemurafenib-Resistant Melanoma Harboring the MEK1-C121S Mutation in a Preclinical Model
Authors: Narita Yusuke , Okamoto Kiyoshi , Kawada Megumi Ikemori , Takase Kazuma , Minoshima Yukinori , Kodama Kotaro , Iwata Masao , Miyamoto Norimasa , Sawada Kohei
Published: January 2014

Many clinical cases of acquired resistance to the BRAF inhibitor vemurafenib have recently been reported. One of the causes of this acquired resistance is the BRAF downstream kinase point mutation MEK1-C121S. This mutation confers resistance to not only vemurafenib, but also to the allosteric MEK inhibitor selumetinib (AZD6244). Here, we investigated the pharmacologic activities and effectiveness of the novel MEK inhibitor E6201 against BRAF (v-raf murine sarcoma viral oncogene homolog B1)-V600E mutant melanoma harboring the MEK1-C121S mutation. A cell-free assay confirmed that E6201 is an ATP-competitive MEK inhibitor, meaning it has a different binding mode with MEK compared with allosteric MEK inhibitors. E6201 is more effective against BRAF-V600E mutant melanoma compared with BRAF wild-type melanoma based on MEK inhibition. We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201. The effectiveness of E6201 in this preclinical study is a result of its binding with MEK1 far from the C121S point mutation so the mutation is unable to influence the MAPK pathway inhibitory activity. These results support further clinical investigation of E6201. Mol Cancer Ther; 13(4); 823–32. ©2014 AACR.