bluuebunny/crossref_metadata_2025 huggingface dataset:
Error Analysis and Compensation of Gyrocompass Alignment for SINS on Moving Base
Authors: Xu Bo , Liu Yang , Shan Wei , Zhang Yi , Wang Guochen
Published: June 2014

An improved method of gyrocompass alignment for strap‐down inertial navigation system (SINS) on moving base assisted with Doppler velocity log (DVL) is proposed in this paper. After analyzing the classical gyrocompass alignment principle on static base, implementation of compass alignment on moving base is given in detail. Furthermore, based on analysis of velocity error, latitude error, and acceleration error on moving base, two improvements are introduced to ensure alignment accuracy and speed: (1) the system parameters are redesigned to decrease the acceleration interference and (2) a data repeated calculation algorithm is used in order to shorten the prolonged alignment time caused by changes in parameters. Simulation and test results indicate that the improved method can realize the alignment on moving base quickly and effectively.
Are Commonly Measured Functional Traits Involved in Tropical Tree Responses to Climate?
Authors: Wagner Fabien , Rossi Vivien , Baraloto Christopher , Bonal Damien , Stahl Clément , Hérault Bruno
Published: June 2014

Climate models predict significant rainfall reduction in Amazonia, reducing water availability for trees. We present how functional traits modulate the tree growth response to climate. We used data from 3 years of bimestrial growth measurements for 204 trees of 53 species in the forest of Paracou, French Guiana. We integrated climate variables from an eddy covariance tower and functional trait values describing life history, leaf, and stem economics. Our results indicated that the measured functional traits are to some extent linked to the response of trees to climate but they are poor predictors of the tree climate-induced growth variation. Tree growth was affected by water availability for most of the species with different species growth strategies in drought conditions. These strategies were linked to some functional traits, especially maximum height and wood density. These results suggest that (i) trees seem adapted to the dry season at Paracou but they show different growth responses to drought, (ii) drought response is linked to growth strategy and is partly explained by functional traits, and (iii) the limited part of the variation of tree growth explained by functional traits may be a strong limiting factor for the prediction of tree growth response to climate.
The Human Plasma Membrane Peripherome: Visualization and Analysis of Interactions
Authors: Nastou Katerina C. , Tsaousis Georgios N. , Kremizas Kimon E. , Litou Zoi I. , Hamodrakas Stavros J.
Published: June 2014

A major part of membrane function is conducted by proteins, both integral and peripheral. Peripheral membrane proteins temporarily adhere to biological membranes, either to the lipid bilayer or to integral membrane proteins with noncovalent interactions. The aim of this study was to construct and analyze the interactions of the human plasma membrane peripheral proteins (peripherome hereinafter). For this purpose, we collected a dataset of peripheral proteins of the human plasma membrane. We also collected a dataset of experimentally verified interactions for these proteins. The interaction network created from this dataset has been visualized using Cytoscape. We grouped the proteins based on their subcellular location and clustered them using the MCL algorithm in order to detect functional modules. Moreover, functional and graph theory based analyses have been performed to assess biological features of the network. Interaction data with drug molecules show that ~10% of peripheral membrane proteins are targets for approved drugs, suggesting their potential implications in disease. In conclusion, we reveal novel features and properties regarding the protein-protein interaction network created by peripheral proteins of the human plasma membrane.
Fixed Point Theorems for Multivalued Mappings Involvingα-Function
Authors: Ali Muhammad Usman , Kiran Quanita , Shahzad Naseer
Published: June 2014

We obtain some fixed point theorems with error estimates for multivalued mappings satisfying a newα-ψ-contractive type condition. Our theorems generalize many existing fixed point theorems, including some fixed point theorems proved forα-ψ-contractive type conditions.
Heat Transfer Analysis of Viscous Incompressible Fluid by Combined Natural Convection and Radiation in an Open Cavity
Authors: Saleem M. , Hossain M. A. , Saha Suvash C. , Gu Y. T.
Published: June 2014

The effect of radiation on natural convection of Newtonian fluid contained in an open
cavity is investigated in this study. The governing partial differential equations are solved numerically
using the Alternate Direct Implicit method together with the Successive Overrelaxation method.
The study is focused on studying the flow pattern and the convective and radiative heat transfer
rates are studied for different values of radiation parameters, namely, the optical thickness of the
fluid, scattering albedo, and the Planck number. It was found that, in the optically thin limit, an
increase in the optical thickness of the fluid raises the temperature and radiation heat transfer of
the fluid. However, a further increase in the optical thickness decreases the radiative heat transfer
rate due to increase in the energy level of the fluid, which ultimately reduces the total heat transfer
rate within the fluid.
A New Approach to General Interpolation Formulae for Bivariate Interpolation
Authors: Zou Le , Tang Shuo
Published: June 2014

General interpolation formulae for bivariate interpolation are established by introducing multiple parameters, which are extensions and improvements of those studied by Tan and Fang. The general interpolation formulae include general interpolation formulae of symmetric branched continued fraction, general interpolation formulae of univariate and bivariate interpolation, univariate block based blending rational interpolation, bivariate block based blending rational interpolation and their dual schemes, and some interpolation form studied by many scholars in recent years. We discuss the interpolation theorem, algorithms, dual interpolation, and special cases and give many kinds of interpolation scheme. Numerical examples are given to show the effectiveness of the method.
Investigation of the Optimal Parameters in Hydrothermal Method for the Synthesis of ZnO Nanorods
Authors: Chen Ying-Chung , Cheng Huan-Yi , Yang Cheng-Fu , Hsieh Yuan-Tai
Published: June 2014

We investigated a two‐step method to deposit the ZnO‐based nanostructure films, including nanorods and nanoflowers. In the first step, sputtering method was used to deposit the ZnO films on SiO2/Si substrates as the seed layer. In the second step, Zn(NO3)2–6H2O and C6H12N4 were used as precursors and hydrothermal process was used as the method to synthesize the ZnO films. After that, the ZnO films were measured by an X‐ray diffraction pattern and a FESEM to analyze their crystallization and morphology. We had found that the ZnO films had three different morphologies synthesized on ZnO/SiO2/Si substrates, including irregular‐plate structure films, nanorod films, and beautiful chrysanthemum‐like clusters (nanoflower films). We would prove that the face direction of ZnO/SiO2/Si substrates in the hydrothermal bottle and deposition time were two important factors to influence the synthesized results of the ZnO films.
Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling
Authors: Lee Chung , Jia Zhenyu , Rahmatpanah Farah , Zhang Qiang , Zi Xiaolin , McClelland Michael , Mercola Dan
Published: June 2014

This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-βand IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-βand IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-βand IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer.
Efficient and Reliable Solar Panels for Small CubeSat Picosatellites
Authors: Vertat Ivo , Vobornik Ales
Published: June 2014

CubeSat picosatellites have a limited area of walls for solar cells assembling and the available area has to be effectively shared with other parts, such as planar antennas, optical sensors, camera lens, and access port. With standard size of solar cell strings, it is not possible to construct a reliable solar panel for CubeSat with redundant strings interconnection. Typical solar panels for CubeSat consist of two solar cell strings serially wired with no redundancy in case of solar string failure. The loss of electric energy from one solar panel can cause a serious problem for most picosatellites due to minimum margin in the blueprints of the picosatellite subsystem power budget. In this paper, we propose a new architecture of solar panels for PilsenCUBE CubeSat with a high level of redundancy in the case of solar string failure or following switched power regulator failure. Our solar panels use a high efficiency triple junction GaInP2/GaAs/Ge in the form of small triangle strings from the Spectrolab Company. A suitable technology for precise solar cell assembling is also discussed, because CubeSat picosatellites are usually developed by small teams with limited access to high-end facilities.
Comparison of Commercial Genetic-Testing Services in Korea with 23andMe Service
Authors: Kim Sollip , Eom Ki-Won , Cho Chong-Rae , Um Tae Hyun
Published: June 2014

Introduction. Genetic testing services for disease prediction, drug responses, and traits are commercially available by several companies in Korea. However, there has been no evaluation study for the accuracy and usefulness of these services. We aimed to compare two genetic testing services popular in Korea with 23andMe service in the United States.Materials and Methods. We compared the results of two persons (one man and one woman) serviced by Hellogene Platinum (Theragen Bio Institute), DNAGPS Optimus (DNAlink), and 23andMe service.Results. Among 3 services, there were differences in the estimation of relative risks for the same disease. For lung cancer, the range of relative risk was from 0.9 to 2.09. These differences were thought to be due to the differences of applied single nucleotide polymorphisms (SNPs) in each service for the calculation of risk. Also, the algorithm and population database would have influence on the estimation of relative disease risks. The concordance rate of SNP calls between DNAGPS Optimus and 23andMe services was 100% (30/30).Conclusions. Our study showed differences in disease risk estimations among three services, although they gave good concordance rate for SNP calls. We realized that the genetic services need further evaluation and standardization, especially in disease risk estimation algorithm.
Exact Solutions for a New Nonlinear KdV-Like Wave Equation Using Simplest Equation Method and Its Variants
Authors: He Yinghui , Zhao Yun-Mei , Long Yao
Published: June 2014

The simplest equation method presents wide applicability to the handling of nonlinear wave equations. In this paper, we focus on the exact solution of a new nonlinear KdV-like wave equation by means of the simplest equation method, the modified simplest equation method and, the extended simplest equation method. The KdV-like wave equation was derived for solitary waves propagating on an interface (liquid-air) with wave motion induced by a harmonic forcing which is more appropriate for the study of thin film mass transfer. Thus finding the exact solutions of this equation is of great importance and interest. By these three methods, many new exact solutions of this equation are obtained.
Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury
Authors: Kumar Jain Ajay , Teckman Jeffrey H.
Published: June 2014

Total parenteral nutrition (TPN), a lifesaving therapy, involves providing nutrition by bypassing the gut. Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD). PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure. The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor signaling, is emerging as a promising mechanism. Rodent models and our piglet TPN model have shown that, during regular feeding, bile acids activate farnesoid X receptor (FXR) in the gut and enhance fibroblast growth factor 19 (FGF19) level. FGF19 regulates bile acid, lipid, and glucose metabolism. We noted reduced FGF19 with TPN use and substantial improvement in FGF19, bilirubin, and metabolic profiles with the FXR agonist chenodeoxycholic acid (CDCA). Additionally, CDCA caused gut growth and enhanced expression of glucagon like peptides (GLPs). GLPs regulate gut trophic effects, insulin, glucose homeostasis, and hepatic steatosis. GLP secretion is regulated by the CDCA activated receptor TGR5. This leads to an important conclusion that, in addition to a disrupted FXR-FGF19 axis, a disrupted TGR5-GLP axis may contribute to TPN related pathologies. Thus modulators of FXR-FGF19 and the TGR5-GLP axis could help bring forward novel treatment strategies.
SCAR: A Coding-Aware Routing Protocol with Self-Recommendation in Static Wireless Ad Hoc Networks
Authors: Wang Jin , Zhu Cenzhe , Chai Teck Yoong , Wong Wai-Choong
Published: June 2014

There have been researchers working on the design of coding-aware routing protocols to exploit the power of network coding in static wireless ad hoc networks. However, most of them have overlooked the fact that routing decisions for multiple flows need to be coordinated in order to achieve maximum throughput. A mechanism to alter prior routing decisions is mandatory for this purpose. In this paper, we propose Self-recommendation coding-aware routing (SCAR), to provide such a mechanism. With intermediate nodes sensing the arrival of new flows, they can send self-recommendations to source nodes, triggering a route-change procedure. In the route-change procedure, adjustments are applied to the route metrics so that the newly recommended route can be fairly weighed without bias. A thorough analysis of coding structures is carried out, and a series of indicators are devised to predict how much throughput benefits we can gain from the mere knowledge of the topology. The rationale behind the protocol design and the effectiveness of the indicators are further justified by a series of simulations. Results show that SCAR can exploit coding opportunities better and provide higher throughput than other coding-aware routing protocols. It is also shown that the opportunity of throughput gain is ubiquitous and it is tested on many typical topologies.
Duration of Type 2 Diabetes and Very Low Density Lipoprotein Levels Are Associated with Cognitive Dysfunction in Metabolic Syndrome
Authors: Yogi-Morren Divya , Galioto Rachel , Strandjord Sarah Elizabeth , Kennedy L. , Manroa Pooja , Kirwan John P. , Kashyap Sangeeta , Gunstad John
Published: June 2014

Type 2 diabetes (T2D) is now recognized as an independent risk factor for accelerated cognitive decline and neurological conditions like Alzheimer’s disease. Less is known about the neurocognitive function of T2D patients with comorbid metabolic syndrome, despite their elevated risk for impairment. Computerized testing in 47 adults with T2D that met criteria for NCEP metabolic syndrome revealed that cognitive impairment was prevalent, including 13% in tests of memory, 50% in attention, and 35% in executive function. Partial correlations showed that longer duration of diabetes was associated with poorer performance on tests of basic attention (r=-0.43), working memory (r=0.43), and executive function (r=0.42). Strong associations between very low density lipoprotein and poor cognitive function also emerged, including tests of set shifting (r=0.47) and cognitive inhibition (r=-0.51). Findings suggest that patients with T2D that meet criteria for metabolic syndrome are at high risk for cognitive impairment. Prospective studies should look to replicate these findings and examine the possible neuroprotective effects of lipid-lowering medication in this population.
Defining Loci in Restriction-Based Reduced Representation Genomic Data from Nonmodel Species: Sources of Bias and Diagnostics for Optimal Clustering
Authors: Ilut Daniel C. , Nydam Marie L. , Hare Matthew P.
Published: June 2014

Next generation sequencing holds great promise for applications of phylogeography, landscape genetics, and population genomics in wild populations of nonmodel species, but the robustness of inferences hinges on careful experimental design and effective bioinformatic removal of predictable artifacts. Addressing this issue, we use published genomes from a tunicate, stickleback, and soybean to illustrate the potential for bioinformatic artifacts and introduce a protocol to minimize two sources of error expected from similarity-based de-novo clustering of stacked reads: the splitting of alleles into different clusters, which creates false homozygosity, and the grouping of paralogs into the same cluster, which creates false heterozygosity. We present an empirical application focused onCiona savignyi, a tunicate with very high SNP heterozygosity (~0.05), because high diversity challenges the computational efficiency of most existing nonmodel pipelines while also potentially exacerbating paralog artifacts. The simulated and empirical data illustrate the advantages of using higher sequence difference clustering thresholds than is typical and demonstrate the utility of our protocol for efficiently identifying an optimum threshold from data without prior knowledge of heterozygosity. The empiricalCiona savignyidata also highlight null alleles as a potentially large source of false homozygosity in restriction-based reduced representation genomic data.
Thermal Resistance across Interfaces Comprising Dimensionally Mismatched Carbon Nanotube‐Graphene Junctions in 3D Carbon Nanomaterials
Authors: Park Jungkyu , Prakash Vikas
Published: June 2014

In the present study, reverse nonequilibrium molecular dynamics is employed to study thermal resistance across interfaces comprising dimensionally mismatched junctions of single layer graphene floors with (6,6) single‐walled carbon nanotube (SWCNT) pillars in 3D carbon nanomaterials. Results obtained from unit cell analysis indicate the presence of notable interfacial thermal resistance in the out‐of‐plane direction (along the longitudinal axis of the SWCNTs) but negligible resistance in the in‐plane direction along the graphene floor. The interfacial thermal resistance in the out‐of‐plane direction is understood to be due to the change in dimensionality as well as phonon spectra mismatch as the phonons propagate from SWCNTs to the graphene sheet and then back again to the SWCNTs. The thermal conductivity of the unit cells was observed to increase nearly linearly with an increase in cell size, that is, pillar height as well as interpillar distance, and approaches a plateau as the pillar height and the interpillar distance approach the critical lengths for ballistic thermal transport in SWCNT and single layer graphene. The results indicate that the thermal transport characteristics of these SWCNT‐graphene hybrid structures can be tuned by controlling the SWCNT‐graphene junction characteristics as well as the unit cell dimensions.
Recent Advances in Heterogeneous Photocatalytic Decolorization of Synthetic Dyes
Authors: Muhd Julkapli Nurhidayatullaili , Bagheri Samira , Bee Abd Hamid Sharifah
Published: June 2014

During the process and operation of the dyes, the wastes produced were commonly found to contain organic and inorganic impurities leading to risks in the ecosystem and biodiversity with the resultant impact on the environment. Improper effluent disposal in aqueous ecosystems leads to reduction of sunlight penetration which in turn diminishes photosynthetic activity, resulting in acute toxic effects on the aquatic flora/fauna and dissolved oxygen concentration. Recently, photodegradation of various synthetic dyes has been studied in terms of their absorbance and the reduction of oxygen content by changes in the concentration of the dye. The advantages that make photocatalytic techniques superior to traditional methods are the ability to remove contaminates in the range of ppb, no generation of polycyclic compounds, higher speed, and lower cost. Semiconductor metal oxides, typically TiO2, ZnO, SnO, NiO, Cu2O, Fe3O4, and also CdS have been utilized as photocatalyst for their nontoxic nature, high photosensitivity, wide band gap and high stability. Various process parameters like photocatalyst dose, pH and initial dye concentrations have been varied and highlighted. Research focused on surface modification of semiconductors and mixed oxide semiconductors by doping them with noble metals (Pt, Pd, Au, and Ag) and organic matter (C, N, Cl, and F) showed enhanced dye degradation compared to corresponding native semiconductors. This paper reviews recent advances in heterogeneous photocatalytic decolorization for the removal of synthetic dyes from water and wastewater. Thus, the main core highlighted in this paper is the critical selection of semiconductors for photocatalysis based on the chemical, physical, and selective nature of the poisoning dyes.
Friction Stir Spot Welding: A Review on Joint Macro- and Microstructure, Property, and Process Modelling
Authors: Yang X. W. , Fu T. , Li W. Y.
Published: June 2014

Friction stir spot welding (FSSW) is a very useful variant of the conventional friction stir welding (FSW), which shows great potential to be a replacement of single-point joining processes like resistance spot welding and riveting. There have been many reports and some industrial applications about FSSW. Based on the open literatures, the process features and variants, macro- and microstructural characteristics, and mechanical properties of the resultant joints and numerical simulations of the FSSW process were summarized. In addition, some applications of FSSW in aerospace, aviation, and automobile industries were also reviewed. Finally, the current problems and issues that existed in FSSW were indicated.
Extended Target Shape Estimation by Fitting B-Spline Curve
Authors: Yang Jin-long , Li Peng , Ge Hong-wei
Published: June 2014

Taking into account the difficulty of shape estimation for the extended targets, a novel algorithm is proposed by fitting the B-spline curve. For the single extended target tracking, the multiple frame statistic technique is introduced to construct the pseudomeasurement sets and the control points are selected to form the B-spline curve. Then the shapes of the extended targets are extracted under the Bayes framework. Furthermore, the proposed shape estimation algorithm is modified suitably and combined with the probability hypothesis density (PHD) filter for multiple extended target tracking. Simulations show that the proposed algorithm has a good performance for shape estimate of any extended targets.
Precomputed Clustering for Movie Recommendation System in Real Time
Authors: Li Bo , Liao Yibin , Qin Zheng
Published: June 2014

A recommendation system delivers customized data (articles, news, images, music, movies, etc.) to its users. As the interest of recommendation systems grows, we started working on the movie recommendation systems. Most research efforts in the fields of movie recommendation system are focusing on discovering the most relevant features from users, or seeking out users who share same tastes as that of the given user as well as recommending the movies according to the liking of these sought users or seeking out users who share a connection with other people (friends, classmates, colleagues, etc.) and make recommendations based on those related people’s tastes. However, little research has focused on recommending movies based on the movie’s features. In this paper, we present a novel idea that applies machine learning techniques to construct a cluster for the movie by implementing a distance matrix based on the movie features and then make movie recommendation in real time. We implement some different clustering methods and evaluate their performance in a real movie forum website owned by one of our authors. This idea can also be used in other types of recommendation systems such as music, news, and articles.
Mutual Defense Scheme for Secure Data Aggregation in Wireless Sensor Networks
Authors: Rong-hua Hu , Xiao-mei Dong , Da-ling Wang
Published: June 2014

As a resource-saving technique, data aggregation has been intensively studied in wireless sensor networks (WSNs). However, existing methods of secure data aggregation in WSNs either (1) cause high communication overhead or (2) cannot defend against compromised member nodes and aggregator nodes at the same time. In this paper, we propose a mutual defense scheme for secure data aggregation, which includes two components, that is, secure sort-group-filter data aggregation algorithm (SSGF) and lightweight TDMA-based monitoring mechanism. The SSGF is to defend against injecting false readings by compromised member nodes, and the monitoring mechanism is to defend against altering the aggregation results by aggregator nodes. In addition, a secure data packet transmission scheme is also presented. Considering that the readings sensed by neighbor nodes exhibit temporal and spatial correlation, a constraint parameter, called maximum tolerant difference (MTD), is introduced and the quantitative criteria for abnormal readings evaluation are given. Both the theoretical analysis and comparative experiments show the feasibility and efficiency of the proposed method.
Bone Health in Type 1 Diabetes: Where We Are Now and How We Should Proceed
Authors: Zhukouskaya Volha V. , Shepelkevich Alla P. , Chiodini Iacopo
Published: June 2014

Type 1 diabetes (T1D) is autoimmune disease with chronic hyperglycaemic state. Besides diabetic retinopathy, nephropathy, and neuropathy, T1D is characterized by poor bone health. The reduced bone mineralization and quality/strength, due to hyperglycemia, hypoinsulinemia, autoimmune inflammation, low levels of insulin growth factor-1 (IGF-1), and vitamin D, lead to vertebral/hip fractures. Young age of T1D manifestation, chronic poor glycemic control, high daily insulin dose, low BMI, reduced renal function, and the presence of complications can be helpful in identifying T1D patients at risk of reduced bone mineral density. Although risk factors for fracture risk are still unknown, chronic poor glycemic control and presence of diabetic complications might raise the suspicion of elevated fracture risk in T1D. In the presence of the risk factors, the assessment of bone mineral density by dual-energy X-ray absorptiometry and the search of asymptomatic vertebral fracture by lateral X-ray radiography of thorax-lumbar spine should be recommended. The improvement of glycemic control may have a beneficial effect on bone in T1D. Several experiments showed promising results on using anabolic pharmacological agents (recombinant IGF-1 and parathyroid hormone) in diabetic rodents with bone disorder. Randomized clinical trials are needed in order to test the possible use of bone anabolic therapies in humans with T1D.
A Regev-Type Fully Homomorphic Encryption Scheme Using Modulus Switching
Authors: Chen Zhigang , Wang Jian , Chen Liqun , Song Xinxia
Published: June 2014

A critical challenge in a fully homomorphic encryption (FHE) scheme is to manage noise. Modulus switching technique is currently the most efficient noise management technique. When using the modulus switching technique to design and implement a FHE scheme, how to choose concrete parameters is an important step, but to our best knowledge, this step has drawn very little attention to the existing FHE researches in the literature. The contributions of this paper are twofold. On one hand, we propose a function of the lower bound of dimension value in the switching techniques depending on the LWE specific security levels. On the other hand, as a case study, we modify the Brakerski FHE scheme (in Crypto 2012) by using the modulus switching technique. We recommend concrete parameter values of our proposed scheme and provide security analysis. Our result shows that the modified FHE scheme is more efficient than the original Brakerski scheme in the same security level.
TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior
Authors: Ai Lingbao , Kim Wan-Ju , Alpay Merve , Tang Ming , Pardo Carolina E. , Hatakeyama Shigetsugu , May W. Stratford , Kladde Michael P. , Heldermon Coy D. , Siegel Erin M. , Brown Kevin D.
Published: June 2014

TRIM29 (ATDC) exhibits a contextual function in cancer, but seems to exert a tumor-suppressor role in breast cancer. Here, we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial–mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene-expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival, increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT. Cancer Res; 74(17); 4875–87. ©2014 AACR.
Neuronal Pentraxin 2 Supports Clear Cell Renal Cell Carcinoma by Activating the AMPA-Selective Glutamate Receptor-4
Authors: von Roemeling Christina A. , Radisky Derek C. , Marlow Laura A. , Cooper Simon J. , Grebe Stefan K. , Anastasiadis Panagiotis Z. , Tun Han W. , Copland John A.
Published: June 2014

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however, the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is overexpressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for patients with ccRCC diagnosed with or at risk of developing metastatic disease. Cancer Res; 74(17); 4796–810. ©2014 AACR.
Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer
Authors: Stallone Giovanni , Cormio Luigi , Netti Giuseppe Stefano , Infante Barbara , Selvaggio Oscar , Fino Giuseppe Di , Ranieri Elena , Bruno Francesca , Prattichizzo Clelia , Sanguedolce Francesca , Tortorella Simona , Bufo Pantaleo , Grandaliano Giuseppe , Carrieri Giuseppe
Published: June 2014

Pentraxin-3 (PTX3) is a member of the pentraxin family of innate immune regulators, which includes C-reactive protein (CRP). PTX3 has been implicated in angiogenesis, proliferation, and immune escape in cancer. In the present study, we evaluated PTX3 tissue expression and serum concentration as a biomarker to discriminate prostatic inflammation and benign prostatic hyperplasia (BPH) from prostate cancer, and to determine whether PTX3 status may predict progression from BPH to prostate cancer. We analyzed 40 patients with biopsy-proven BPH who underwent a second prostate biopsy 12 to 36 months later when they were diagnosed with prostate cancer or inflammation/BPH (n = 20 patients each group). Furthermore, we evaluated PTX3 serum concentrations in an independent set of patients with biopsy-proven inflammation/BPH (n = 61) and prostate cancer (n = 56). We found reduced PTX3 tissue expression in patients with prostatic inflammation/BPH compared with patients who developed prostate cancer. In the latter group, there was an increase in PTX3 tissue expression between the first and second prostate biopsy. PTX3 serum levels were also higher in patients with prostate cancer than in patients with inflammation/BPH. In contrast, there was no difference in serum PSA or CRP levels in these two groups. ROC curve analysis confirmed the reliability of PTX3 serum levels in predicting prostate cancer development, identifying a cutoff value of 3.25 ng/mL with a sensitivity and a specificity of 89.3% and 88.5%, respectively. In summary, our results encourage further evaluation of PTX3 as a tissue biopsy and blood-borne biomarker to discriminate BPH from prostate cancer. Cancer Res; 74(16); 4230–8. ©2014 AACR.
Association of Insulin-Related Serum Factors with Colorectal Polyp Number and Type in Adult Males
Authors: Comstock Sarah S. , Xu Diana , Hortos Kari , Kovan Bruce , McCaskey Sarah , Pathak Dorothy R. , Fenton Jenifer I.
Published: June 2014

Background: Dysregulated insulin signaling is thought to contribute to cancer risk.

Methods: To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48–65 years) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type.

Results: Males with serum C-peptide concentration >3.3 ng/mL were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/mL. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (P = 0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/mL were 0.25 times less likely to have ≥3 polyps relative to no polyps compared with males with sRAGE ≤94.5 pg/mL. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (P = 0.03). Compared with males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/mL, males with a serum VEGF concentration >184.2 pg/mL were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (P = 0.049).

Conclusions: Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy.

Impact: Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals. Cancer Epidemiol Biomarkers Prev; 23(9); 1843–51. ©2014 AACR.
Reversible LSD1 Inhibition Interferes with Global EWS/ETS Transcriptional Activity and Impedes Ewing Sarcoma Tumor Growth
Authors: Sankar Savita , Theisen Emily R. , Bearss Jared , Mulvihill Timothy , Hoffman Laura M. , Sorna Venkataswamy , Beckerle Mary C. , Sharma Sunil , Lessnick Stephen L.
Published: June 2014

Purpose: Ewing sarcoma is a pediatric bone tumor that absolutely relies on the transcriptional activity of the EWS/ETS family of fusion oncoproteins. While the most common fusion, EWS/FLI, utilizes lysine-specific demethylase 1 (LSD1) to repress critical tumor suppressors, small-molecule blockade of LSD1 has not yet been thoroughly explored as a therapeutic approach for Ewing sarcoma. We therefore evaluated the translational potential of potent and specific LSD1 inhibition with HCI2509 on the transcriptional program of both EWS/FLI and EWS/ERG as well as the downstream oncogenic phenotypes driven by EWS/ETS fusions in both in vitro and in vivo models of Ewing sarcoma.

Experimental Design: RNA-seq was used to compare the transcriptional profiles of EWS/FLI, EWS/ERG, and treatment with HCI2509 in both EWS/FLI- and EWS/ERG-containing cell lines. We then evaluated morphologic phenotypes of treated cells with immunofluorescence. The induction of apoptosis was evaluated using caspase-3/7 activation and TUNEL staining. Colony forming assays were used to test oncogenic transformation and xenograft studies with patient-derived cell lines were used to evaluate the effects of HCI2509 on tumorigenesis.

Results: HCI2509 caused a dramatic reversal of both the up- and downregulated transcriptional profiles of EWS/FLI and EWS/ERG accompanied by the induction of apoptosis and disruption of morphologic and oncogenic phenotypes modulated by EWS/FLI. Importantly, HCI2509 displayed single-agent efficacy in multiple xenograft models.

Conclusions: These data support epigenetic modulation with HCI2509 as a therapeutic strategy for Ewing sarcoma, and highlight a critical dual role for LSD1 in the oncogenic transcriptional activity of EWS/ETS proteins. Clin Cancer Res; 20(17); 4584–97. ©2014 AACR.
Carcinogen-Induced Skin Tumor Development Requires Leukocytic Expression of the Transcription Factor Runx3
Authors: Bauer Omri , Hantisteanu Shay , Lotem Joseph , Groner Yoram
Published: June 2014

Carcinogen-induced skin tumorigenesis depends heavily on proinflammatory tumor-promoting processes. Here, we show that leukocytic Runx3 expression is central to the two-stage DMBA/TPA-induced skin tumorigenesis. Runx3-null mice were highly resistant to this process and concomitant ablation of Runx3 in dendritic and T cells fully recapitulated this resistance. Mechanistically, this resistance was associated with a shift in the skin cytokine milieu toward a tumor nonpermissive microenvironment. Specifically, leukocytic Runx3 loss substantially increased the antitumorigenic cytokine thymic stromal lymphopoietin (TSLP) and profoundly decreased two protumorigenic cytokines, interleukin-17a and osteopontin. Therefore, inflammation-mediated tumor promotion requires leukocytic Runx3 expression, as its loss creates a unique cytokine composition that polarizes the tumor microenvironment to a potent antitumorigenic state. Cancer Prev Res; 7(9); 913–26. ©2014 AACR.
Is HCRTR2 a Genetic Risk Factor for Alzheimer's Disease?
Authors: Gallone Salvatore , Boschi Silvia , Rubino Elisa , De Martino Paola , Scarpini Elio , Galimberti Daniela , Fenoglio Chiara , Acutis Pier Luigi , Maniaci Maria Grazia , Pinessi Lorenzo , Rainero Innocenzo
Published: June 2014

Backgrounds/Aims: Alzheimer's disease (AD) is one of the main types of dementia affecting about 50-55% of all demented patients. Sleep disturbances in AD patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble the core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. The aim of our study was to investigate whether genetic variants in the hypocretin (HCRT) and in the hypocretin receptors 1 and 2 (HCRTR1, HCRTR2) genes could modify the occurrence and the clinical features of AD and to examine if these possible variants influence the role of the protein in sleep regulation. Methods: Using a case-control strategy, we genotyped 388 AD patients and 272 controls for 10 SNPs in the HCRT, HCRTR1 and HCRTR2 genes. In order to evaluate which residues belong to the HCRTR2 binding site, we built a molecular model. Results: The genotypic and allelic frequencies of the rs2653349 polymorphism were different (χ2 = 5.77, p = 0.016; χ2 = 6.728, p = 0.035) between AD patients and controls. The carriage of the G allele was associated with an increased AD risk (OR 2.53; 95% CI 1.10-5.80). No significant differences were found in the distribution of either genotypic or allelic frequencies between cases and controls in the HCRTR1 polymorphisms rs2271933, rs10914456 and rs4949449 and in the HCRTR2 polymorphism rs3122156. Conclusion: Our data support the hypothesis that the HCRTR2 gene is likely to be a risk factor for AD. The increased risk inferred is quite small, but in the context of a multi-factorial disease, the presence of this polymorphism may significantly contribute to influencing the susceptibility for AD by interacting with other unknown genetic or environmental factors in sleep regulation.
Motor Cortex Excitability Changes in Mild Alzheimer's Disease Are Reversed by Donepezil
Authors: Balla Christina , Maertens de Noordhout Alain , Pepin Jean Louis
Published: June 2014

Background: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). Methods: We used transcranial magnetic stimulation to measure the active cortical motor threshold (ACMT) in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could have a direct effect on the excitability of the motor cortex. Results: An increase of the ACMT was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the threshold did not differ significantly from normal subjects. Conclusions: The results suggest an early functional impairment of cholinergic neurotransmission in AD, which is associated to early changes in the excitability of the motor system.
Modified FOLFOX6 Chemotherapy in Patients with Metastatic Urachal Cancer
Authors: Yanagihara Yutaka , Tanji Nozomu , Miura Noriyoshi , Shirato Akitomi , Nishimura Kenichi , Fukumoto Tetsuya , Azuma Koji , Miyauchi Yuki , Kikugawa Tadahiko , Yokoyama Masayoshi
Published: June 2014

Background: To improve the prognosis of patients with urachal cancer and establish an effective chemotherapeutic regimen for distant metastases. Methods: We conducted a retrospective study to evaluate the efficacy and safety of a modified combination of 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) therapy in patients with metastatic urachal cancer. Results: Five patients were treated with mFOLFOX6. Their median age was 65 years (range 41-80). The median follow-up time was 42 months (range 18-46). Two of the 5 patients (40%) showed an objective response: 1 achieved a clinically complete response and 1 a partial response. The grade 3/4 toxicity associated with this regimen was primarily neutropenia, but febrile neutropenia was not observed. Oxaliplatin treatment was discontinued because of a grade 2 allergic reaction in 1 patient. Grade 2 peripheral sensory neuropathy caused by oxaliplatin was observed in 2 patients, and the OPTIMOX (stop and go) approach had to be adopted. Conclusions: mFOLFOX6 appears to be effective for the treatment of metastatic urachal cancer.
Prognostic Significance of Serum Beta-2 Microglobulin in Patients with Non-Hodgkin Lymphoma
Authors: Wu Li , Wang Tong , Gui Wei , Lin Hualiang , Xie Kaipeng , Wang Hui , Gao Tao , Zhang Xiuxiu , Liu Lei , Han Ting , Tian Yuan , Hou Lifang
Published: June 2014

Background and Objective: Elevated serum beta-2 microglobulin (β2-M) has previously been reported in non-Hodgkin lymphoma (NHL) patients. This study examined the association between serum β2-M and the prognosis of NHL and analyzed its predictive value. Method: A total of 287 NHL patients from Taiyuan, Shanxi, China, participated in a prospective cohort study between 2008 and 2011. Overall survival (OS) was compared between NHL patients with high and normal β2-M levels using the log-rank test. Three standard Cox regression models including the International Prognostic Index (IPI) score, β2-M or IPI score + β2-M as independent variables were constructed. The time-dependent receiver operating characteristic curves method and C index were used to examine the tendency of the models' predictive accuracy over time. Results: NHL patients with elevated β2-M values had worse OS (p < 0.001) and higher mortality risk (HR = 1.93, 95% CI 1.37-2.77, p < 0.001) than patients with normal β2-M values. There were statistically significant differences between the C indexes for the models with IPI + β2-M, IPI or β2-M alone (p < 0.001). Conclusion: Our results demonstrated an association between serum β2-M and NHL prognosis. Combining β2-M with IPI may help to improve the prognostic accuracy of NHL.
Serum 25-Hydroxyvitamin D and Cognitive Decline: A Longitudinal Study among Non-Demented Older Adults
Authors: Perna Laura , Mons Ute , Kliegel Matthias , Brenner Hermann
Published: June 2014

Background/Aims: Very few studies have investigated the longitudinal association between serum levels of 25-hydroxyvitamin D [25(OH)D] and cognitive impairment not due to dementia. This longitudinal study analysed 25(OH)D and the risk of cognitive decline among non-demented older adults. Methods: A subsample of the ESTHER cohort study, aged ≥70 years, was assessed with the Cognitive Telephone Screening Instrument (COGTEL) and underwent 25(OH)D measurements standardized with a reference method (n = 1,302). After an average follow-up of 4.6 years, 527 participants had repeated COGTEL testing and were eligible for analysis. Linear regression models were used to assess longitudinal associations between 25(OH)D levels and cognitive function. Possible practice effects of repeated cognitive testing were addressed with the reliable change index. Results: A trend of a more pronounced cognitive decline with lower vitamin D levels was observed among both women and men, with a statistically significant difference in COGTEL scores in the lowest vitamin D quintile of the total sample. Conclusions: This study indicates that low levels of vitamin D might be associated with cognitive decline among non-demented elderly individuals and highlights the need for further large-scale prospective studies to clarify the potential role of vitamin D in cognitive function at an old age.
O escore de risco de Framingham para doenças cardiovasculares
Authors: Lotufo Paulo Andrade
Published: June 2014

As doenças cardiovasculares são a principal causa de morte no Brasil. Os principais fatores de risco para essas doenças são a hipertensão arterial, a dislipidemia, tabagismo e diabetes. Uma fórmula de previsão na população em geral da probabilidade de doença coronariana é calculada baseada nos resultados do Framingham Heart Study. De acordo com faixa etária, sexo, valores de pressão arterial sistólica, valores da razão entre o colesterol total e a fração HDL, presença de tabagismo e diagnóstico de diabetes, é possível estabelecer o risco de infarto do miocárdio e angina do peito em dez anos. O escore de Framingham pode ser útil na comparação de populações, mas traz pouca utilidade na prática clínica.