bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pathway of Collagen Secretion
Authors: Malhotra Vivek , Erlmann Patrik
Published: September 2015

COPII vesicles mediate export of secretory cargo from the endoplasmic reticulum (ER). However, a standard COPII vesicle with a diameter of 60–90 nm is too small to export collagens that are composed of rigid triple helices of up to 400 nm in length. How do cells pack and secrete such bulky molecules? This issue is fundamentally important, as collagens constitute approximately 25% of our dry body weight and are essential for almost all cell-cell interactions. Recently, a potential mechanism for the biogenesis of mega-transport carriers was identified, involving packing collagens and increasing the size of COPII coats. Packing is mediated by TANGO1, which binds procollagen VII in the lumen and interacts with the COPII proteins Sec23/Sec24 on the cytoplasmic side of the ER. Cullin3, an E3 ligase, and its specific adaptor protein, KLHL12, ubiquitinate Sec31, which could increase the size of COPII coats. Recruitment of these proteins and their specific interactors into COPII-mediated vesicle biogenesis may be all that is needed for the export of bulky collagens from the ER. Nonetheless, we present an alternative pathway in which TANGO1 and COPII cooperate to export collagens without generating a mega-transport carrier.
Centromere Associations in Meiotic Chromosome Pairing
Authors: Da Ines Olivier , White Charles I.
Published: September 2015

Production of gametes of halved ploidy for sexual reproduction requires a specialized cell division called meiosis. The fusion of two gametes restores the original ploidy in the new generation, and meiosis thus stabilizes ploidy across generations. To ensure balanced distribution of chromosomes, pairs of homologous chromosomes (homologs) must recognize each other and pair in the first meiotic division. Recombination plays a key role in this in most studied species, but it is not the only actor and particular chromosomal regions are known to facilitate the meiotic pairing of homologs. In this review, we focus on the roles of centromeres and in particular on the clustering and pairwise associations of nonhomologous centromeres that precede stable pairing between homologs. Although details vary from species to species, it is becoming increasingly clear that these associations play active roles in the meiotic chromosome pairing process, analogous to those of the telomere bouquet.
AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle
Authors: Fentz Joachim , Kjøbsted Rasmus , Kristensen Caroline Maag , Hingst Janne Rasmus , Birk Jesper Bratz , Gudiksen Anders , Foretz Marc , Schjerling Peter , Viollet Benoit , Pilegaard Henriette , Wojtaszewski Jørgen F. P.
Published: September 2015

Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity. Adaptations in skeletal muscle by pharmacologically induced activation of 5′-AMP-activated protein kinase (AMPK) are dependent on the AMPKα2 subunit. We hypothesized that exercise training-induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKα wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPKα mdKO mice ran less than WT. Maximal running speed was lower in AMPKα mdKO than in WT mice but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1), cytochrome c, hexokinase II, plasma membrane fatty acid-binding protein, and citrate synthase activity more in AMPKα WT than in mdKO muscle. However, analysis of a subgroup of mice matched for running distance revealed that only UQCRC1 protein content increased more in WT than in mdKO mice with exercise training. Thus, AMPKα1 and -α2 subunits are important for acute exercise-induced mRNA responses of some genes and may be involved in regulating basal metabolic protein expression but seem to be less important in exercise training-induced adaptations in metabolic proteins.
Dominant negative FADD dissipates the proapoptotic signalosome of the unfolded protein response in diabetic embryopathy
Authors: Wang Fang , Weng Hongbo , Quon Michael J. , Yu Jingwen , Wang Jian-Ying , Hueber Anne-Odile , Yang Peixin
Published: September 2015

Endoplasmic reticulum (ER) stress and caspase 8-dependent apoptosis are two interlinked causal events in maternal diabetes-induced neural tube defects (NTDs). The inositol-requiring enzyme 1α (IRE1α) signalosome mediates the proapoptotic effect of ER stress. Diabetes increases tumor necrosis factor receptor type 1R-associated death domain (TRADD) expression. Here, we revealed two new unfolded protein response (UPR) regulators, TRADD and Fas-associated protein with death domain (FADD). TRADD interacted with both the IRE1α-TRAF2-ASK1 complex and FADD. In vivo overexpression of a FADD dominant negative (FADD-DN) mutant lacking the death effector domain disrupted diabetes-induced IRE1α signalosome and suppressed ER stress and caspase 8-dependent apoptosis, leading to NTD prevention. FADD-DN abrogated ER stress markers and blocked the JNK1/2-ASK1 pathway. Diabetes-induced mitochondrial translocation of proapoptotic Bcl-2 members mitochondrial dysfunction and caspase cleavage were also alleviated by FADD-DN. In vitro TRADD overexpression triggered UPR and ER stress before manifestation of caspase 3 and caspase 8 cleavage and apoptosis. FADD-DN overexpression repressed high glucose- or TRADD overexpression-induced IRE1α phosphorylation, its downstream proapoptotic kinase activation and endonuclease activities, and apoptosis. FADD-DN also attenuated tunicamycin-induced UPR and ER stress. These findings suggest that TRADD participates in the IRE1α signalosome and induces UPR and ER stress and that the association between TRADD and FADD is essential for diabetes- or high glucose-induced UPR and ER stress.
Diabetes Burden in Urban and Rural Senegalese Populations: A Cross-Sectional Study in 2012
Authors: Seck S. M. , Dia D. G. , Doupa D. , Diop-Dia A. , Thiam I. , Ndong M. , Gueye L.
Published: September 2015

Diabetes represents a challenging global health issue in the 21st century. Data from sub-Saharan African populations are scarce and are usually restricted to urban settings. The objective of this study was to compare prevalence and risk factors of diabetes in rural and urban areas in Senegal.Methods.In a community-based survey between January and May 2012, we included 1027 adults aged≥18 years living in northern Senegal. Sociodemographic, clinical, and biological data were collected during household visits. Multivariate logistic regression was performed to identify factors associated with diabetes.Results.Mean age of participants was48.0±16.9years and 65.7% were female. Participants from urban area represented 55.7%. The age-standardized prevalence of diabetes was 7.6% (6.0% in men versus 9.0% in women). Prevalence of diabetes was higher in urban areas (8.1%) compared to rural areas (4.6%). Disease awareness rate was 43%. After multivariate analysis, age (OR = 1.63,p=0.001), familial history of diabetes (OR = 1.42,p=0.001), and abdominal obesity (OR = 1.17,p=0.05) were associated with diabetes.Conclusion.Diabetes is frequent in urban and rural areas in Senegal. Awareness rate is very low among populations. Age, family history of diabetes, and abdominal obesity are the main risk factors identified.
Endothelial‐Leukocyte Interaction in Severe Malaria: Beyond the Brain
Authors: Souza Mariana C. , Padua Tatiana A. , Henriques Maria G.
Published: September 2015

Malaria is the most important parasitic disease worldwide, accounting for 1 million deaths each year. Severe malaria is a systemic illness characterized by dysfunction of brain tissue and of one or more peripheral organs as lungs and kidney. The most severe and most studied form of malaria is associated with cerebral complications due to capillary congestion and the adhesion of infected erythrocytes, platelets, and leukocytes to brain vasculature. Thus, leukocyte rolling and adhesion in the brain vascular bed during severe malaria is singular and distinct from other models of inflammation. The leukocyte/endothelium interaction and neutrophil accumulation are also observed in the lungs. However, lung interactions differ from brain interactions, likely due to differences in the blood‐brain barrier and blood‐air barrier tight junction composition of the brain and lung endothelium. Here, we review the importance of endothelial dysfunction and the mechanism of leukocyte/endothelium interaction during severe malaria. Furthermore, we hypothesize a possible use of adjunctive therapies to antimalarial drugs that target the interaction between the leukocytes and the endothelium.
Implementation and Analysis of Clustering Techniques Applied on Pocket Switched Network
Authors: Ali Muhammad , Fida Mah-Rukh , Arsalaan Ameer Shakayb , Adnan Awais
Published: September 2015

Clustering is an extraction of closely knitted groups from a set of nodes. Its benefits in social network range from applying marketing schemes on an appropriate interest group to social network analysis. It is also considered an important tool for efficient communication in an intermittent Pocket Switched Network (PSN). Contact probability between mobile devices in disrupted social networks greatly depends upon the mobility profile and level of relationships between the device holders. Unlike flat routing, scalable and efficient routing in these networks is highly dependent upon accurate derivation of social circles or clusters. This paper therefore evaluates existing clustering techniques for terrestrial social network with the end aim of minimizing communication overhead by identifying those message carriers that can bring message closer to destination node. In order to ensure intercluster routing, modification in existing schemes is proposed so as to detect bridge nodes between single hop destination clusters and to find path towards a disjoint destination cluster.
Risk Factors Associated with Cognitive Decline after Cardiac Surgery: A Systematic Review
Authors: Patel Nikil , Minhas Jatinder S. , Chung Emma M. L.
Published: September 2015

Modern day cardiac surgery evolved upon the advent of cardiopulmonary bypass machines (CPB) in the 1950s. Following this development, cardiac surgery in recent years has improved significantly. Despite such advances and the introduction of new technologies, neurological sequelae after cardiac surgery still exist. Ischaemic stroke, delirium, and cognitive impairment cause significant morbidity and mortality and unfortunately remain common complications. Postoperative cognitive decline (POCD) is believed to be associated with the presence of new ischaemic lesions originating from emboli entering the cerebral circulation during surgery. Cardiopulmonary bypass was thought to be the reason of POCD, but randomised controlled trials comparing with off-pump surgery show contradictory results. Attention has now turned to the growing evidence that perioperative risk factors, as well as patient-related risk factors, play an important role in early and late POCD. Clearly, identifying the mechanism of POCD is challenging. The purpose of this systematic review is to discuss the literature that has investigated patient and perioperative risk factors to better understand the magnitude of the risk factors associated with POCD after cardiac surgery.
The Application of Stefan Problem in Calculating the Lateral Movement of Steam Chamber in SAGD
Authors: Chen Xiong , Nie Ren-Shi , Jia Yong-Lu , Sang Lin-Xiang
Published: September 2015

It is extremely important to monitor the development of steam chambers in reservoirs in the process of SAGD (Steam Assisted Gravity Drainage). By analyzing the temperature data of monitoring wells, the extending velocity and direction of steam chamber can be obtained, which helps to regulate and improve production effectively. Based on Stefan’s inverse problem, a mathematical model is established in this paper for acquiring the extending velocity of steam chamber by using the temperature data of monitoring wells. Mathematical methods are utilized to solve the model such as Fourier transformation as well as an analytic solution using the moving velocity of steam chamber’s edges. Finally, sensitivity analyses concerning some factors such as the formation heat transfer coefficient, the temperature of steam chamber, and the rate of temperature rise of monitoring wells are made. Field application showed that the model can be used to calculate the moving velocity in real time and determine the boundary scope of the steam chambers easily.
Implications of Renal Denervation Therapy in Patients with Sleep Apnea
Authors: Jaén-Águila Fernando , Vargas-Hitos José Antonio , Mediavilla-García Juan Diego
Published: September 2015

Obstructive sleep apnea (OSA) syndrome is a prevalent condition characterized by repeated episodes of obstruction of the upper airway, leading to intermittent hypoxemia and important endothelial and anatomical dysfunctions that cause cardiovascular and cerebrovascular disease. The finding of the relationship between OSA and hypertension, especially resistant hypertension (RHT), has increased the interest in therapeutic strategies that affect renal sympathetic activity in these patients. The observational studies published until now demonstrated that renal denervation therapy can reduce the severity of OSA syndrome. Renal sympathetic denervation (RDN) could be a future therapeutic possibility for conditions other than RHT, such as atrial fibrillation, heart failure, obesity, and OSA syndrome, where renal sympathetic system plays an important physiological role. The aim of this review was to elucidate the implications of renal sympathetic activity in OSA syndrome.
Cardiac‐Restricted IGF‐1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction
Authors: Gallego-Colon Enrique , Sampson Robert D. , Sattler Susanne , Schneider Michael D. , Rosenthal Nadia , Tonkin Joanne
Published: September 2015

Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin‐like growth factor‐1 Ea (IGF‐1Ea) propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac‐specific IGF‐1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF‐1Ea regulated expression of key metalloproteinases (MMP‐2 and MMP‐9), their inhibitors (TIMP‐1 and TIMP‐2), and collagen types (Col 1α1 and Col 1α3) in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti‐inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF‐1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.
Weighted Residual Method for Diffraction of Plane P-Waves in a 2D Elastic Half-Space Revisited: On an Almost Circular Arbitrary-Shaped Canyon
Authors: Lee Vincent W. , Brandow Heather P.
Published: September 2015

Scattering and diffraction of elastic in-plane P- and SV-waves by a surface topography such as an elastic canyon at the surface of a half-space is a classical problem which has been studied by earthquake engineers and strong-motion seismologists for over forty years. The case of out-of-plane SH-waves on the same elastic canyon that is semicircular in shape on the half-space surface is the first such problem that was solved by analytic closed-form solutions over forty years ago by Trifunac. The corresponding case of in-plane P- and SV-waves on the same circular canyon is a much more complicated problem because the in-plane P- and SV-scattered-waves have different wave speeds and together they must have zero normal and shear stresses at the half-space surface. It is not until recently in 2014 that analytic solution for such problem is found by the author in the work of Lee and Liu. This paper uses the technique of Lee and Liu of defining these stress-free scattered waves to solve the problem of the scattering and diffraction of these in-plane waves on an on an almost-circular surface canyon that is arbitrary in shape.
Robotically Assisted Single Anastomosis Duodenoileal Bypass after Previous Sleeve Gastrectomy Implementing High Valuable Technology for Complex Procedures
Authors: Vilallonga Ramon , Fort José Manuel , Caubet Enric , Gonzalez Oscar , Balibrea José Maria , Ciudin Andrea , Armengol Manel
Published: September 2015

Staged bariatric procedures in high risk patients are a common used strategy for morbid obese patients nowadays. After previous sleeve gastrectomy, surgical treatments in order to complete weight loss or comorbidities improvements or resolutions are possible. One strategy is to perform a novel technique named SADI (single anastomosis duodenoileal bypass-sleeve). We present the technique for totally intracorporeal robotically assisted SADI using five ports and a liver retractor. We aim to see if the robotic technology offers more advantageous anastomosis and dissection obtained by the robotic approach in comparison to standard laparoscopy. The safety, feasibility, and reproducibility of a minimally invasive robotic surgical approach to complex abdominal operations such as SADI are discussed.
An Improved RSSI-Based Positioning Method Using Sector Transmission Model and Distance Optimization Technique
Authors: Zhu Haiping , Alsharari Talal
Published: September 2015

This paper focuses on the positioning algorithm suitable for harsh indoor environment such as manufacturing workshop in which the interferences from different directions cannot be neglected. The positioning algorithm is an improved Received Signal Strength Indication- (RSSI-) based ranging method. To preprocess the RSSI data Gaussian filter and mean filter are adopted. A sector transmission model is constructed and applied to divide the area around the anchor node into several sectors, and the shadowing model of each sector is measured. Then the average of all RSSI values in a particular sector is considered as the final RSSI value for distance calculation. The calculated distances designated for trilateration are also optimized to eliminate the abnormal distances from positioning calculations. Positioning experiment is designed via ZigBee facilities. The results show that the proposed algorithm greatly improves the positioning accuracy and stability; for instance, the average positioning error is reduced from 1.32 m to 0.79 m. Moreover, this study also proves that the node position has great influence on the positioning accuracy.
Multicriteria Personnel Selection by the Modified Fuzzy VIKOR Method
Authors: Alguliyev Rasim M. , Aliguliyev Ramiz M. , Mahmudova Rasmiyya S.
Published: September 2015

Personnel evaluation is an important process in human resource management. The multicriteria nature and the presence of both qualitative and quantitative factors make it considerably more complex. In this study, a fuzzy hybrid multicriteria decision‐making (MCDM) model is proposed to personnel evaluation. This model solves personnel evaluation problem in a fuzzy environment where both criteria and weights could be fuzzy sets. The triangular fuzzy numbers are used to evaluate the suitability of personnel and the approximate reasoning of linguistic values. For evaluation, we have selected five information culture criteria. The weights of the criteria were calculated using worst‐case method. After that, modified fuzzy VIKOR is proposed to rank the alternatives. The outcome of this research is ranking and selecting best alternative with the help of fuzzy VIKOR and modified fuzzy VIKOR techniques. A comparative analysis of results by fuzzy VIKOR and modified fuzzy VIKOR methods is presented. Experiments showed that the proposed modified fuzzy VIKOR method has some advantages over fuzzy VIKOR method. Firstly, from a computational complexity point of view, the presented model is effective. Secondly, compared to fuzzy VIKOR method, it has high acceptable advantage compared to fuzzy VIKOR method.
Synthesis and Optimization of Visible Light Active BiVO4Photocatalysts for the Degradation of RhB
Authors: Ran Rong , McEvoy Joanne Gamage , Zhang Zisheng
Published: September 2015

Monoclinic BiVO4powders were synthesized via a novel route using potassium metavanadate (KVO3) prepared by calcination of K2CO3and V2O5as a starting material and followed by hydrothermal treatment and were investigated for the degradation of Rhodamine B (RhB) under visible light irradiation. The synthesized BiVO4particles were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and UV-Visible (UV-Vis) light diffuse reflectance spectrophotometry. The synthesis produced pure monoclinic BiVO4particles with multimorphological features containing flower-like, flake-ball, flake, cuboid-like, and plate-like shapes and exhibited strong absorption in the visible light range. The BiVO4prepared via KVO3possessed excellent photocatalytic activity for the degradation of RhB under visible light. The performance of this catalyst was found to be superior to other BiVO4photocatalysts prepared via ammonium metavanadate (NH4VO3) using coprecipitation, combustion, and calcination methods reported in literature, respectively.
Ultra‐Quasi‐Metrically Tight Extensions of Ultra‐Quasi‐Metric Spaces
Authors: Agyingi Collins Amburo
Published: September 2015

The concept of the tight extension of a metric space was introduced and studied by Dress. It is known that Dress theory is equivalent to the theory of the injective hull of a metric space independently discussed by Isbell some years earlier. Dress showed in particular that for a metric space X the tight extension TX is maximal among the tight extensions of X. In a previous work with P. Haihambo and H.‐P. Künzi, we constructed the tight extension of a T0‐quasi‐metric space. In this paper, we continue these investigations by presenting a similar construction in the category of UQP‐metric spaces and nonexpansive maps.
Image Denoising Based on Improved Wavelet Threshold Function for Wireless Camera Networks and Transmissions
Authors: Wang Xiaoyu , Ou Xiaoxu , Chen Bo-Wei , Kim Mucheol
Published: September 2015

A new wavelet threshold denoising function and an improved threshold are proposed. It not only retains the advantages of hard and soft denoising functions but also overcomes the disadvantages of the continuity problem of hard denoising function and the constant deviation of the soft denoising function in the new method. In the case of the improved threshold conditions, the new threshold function has a better performance in outstanding image details. It can adapt to different images by joining an adjusting factor. Simulation results show that the new threshold function has a better ability of performing image details and a higher peak signal to noise ratio (PSNR).
A Fault Detection Filtering for Networked Control Systems Based on Balanced Reduced-Order
Authors: Dai Da-Meng
Published: September 2015

Due to the probability of the packet dropout in the networked control systems, a balanced reduced-order fault detection filter is proposed. In this paper, we first analyze the packet dropout effects in the networked control systems. Then, in order to obtain a robust fault detector for the packet dropout, we use the balanced structure to construct a reduced-order model for residual dynamics. Simulation results are provided to testify the proposed method.
Cases ofEchinococcus granulosusSensu Stricto Isolated from Polish Patients: Imported or Indigenous?
Authors: Dybicz Monika , Borkowski Piotr Karol , Dąbrowska Julia , Chomicz Lidia
Published: September 2015

The cases of nine Polish patients with diagnosed cystic echinococcosis (CE) were examined. A total of nine isolates obtained postoperatively were investigated using PCR and sequencing. The mitochondrial region ofnad1gene was amplified. This PCR and sequencing analysis revealed the presence ofEchinococcus canadensisG7 in seven patients andE. granulosusG1 in two patients. These data demonstrate thatE. canadensisis the predominant causative agent of human cystic echinococcosis in Poland.E. granulosusG1 detection in Polish patients suggests that the parasite was imported; however it does not exclude the possibility that these cases could have been of Polish origin.
Spindle Cell Lipoma Occurring in the Buccal Mucosa: An Unusual Location of This Benign Lipomatous Neoplasm
Authors: Milhan Noala Vicensoto Moreira , Cavalcante Ana Sueli Rodrigues , Marques Yonara Maria Freire Soares , Carvalho Yasmin Rodarte , Anbinder Ana Lia
Published: September 2015

Spindle cell lipoma is a benign lipomatous neoplasm, which rarely occurs in the oral cavity. The aims of this paper are to report a case of spindle cell lipoma located in buccal mucosa and discuss the main clinical, histological, and immunohistochemical findings of this entity. Thus, we report a 4-year history of an asymptomatic smooth surface nodule in an elderly Caucasian man with clinical hypothesis of fibroma. The histopathological examination showed spindle cells, mature adipose tissue, and many mast cells in a stroma of connective tissue presenting ropey collagen fibers bundles. After immunohistochemical analysis, the final diagnosis was spindle cell lipoma.
New Numerical Solution of von Karman Equation of Lengthwise Rolling
Authors: Pernis Rudolf , Kvackaj Tibor
Published: September 2015

The calculation of average material contact pressure to rolls base on mathematical theory of rolling process given by Karman equation was solved by many authors. The solutions reported by authors are used simplifications for solution of Karman equation. The simplifications are based on two cases for approximation of the circular arch: (a) by polygonal curve and (b) by parabola. The contribution of the present paper for solution of two-dimensional differential equation of rolling is based on description of the circular arch by equation of a circle. The new term relative stress as nondimensional variable was defined. The result from derived mathematical models can be calculated following variables: normal contact stress distribution, front and back tensions, angle of neutral point, coefficient of the arm of rolling force, rolling force, and rolling torque during rolling process. Laboratory cold rolled experiment of CuZn30 brass material was performed. Work hardening during brass processing was calculated. Comparison of theoretical values of normal contact stress with values of normal contact stress obtained from cold rolling experiment was performed. The calculations were not concluded with roll flattening.
Synthetic Aperture Radar Image Background Clutter Fitting Using SKS + MoM-BasedG0Distribution
Authors: Zhu Zhengwei , Zhou Jianjiang , Chu Hongyu
Published: September 2015

G0distribution can accurately model various background clutters in the single-look and multilook synthetic aperture radar (SAR) images and is one of the most important statistic models in the field of SAR image clutter modeling. However, the parameter estimation ofG0distribution is difficult, which greatly limits the application of the distribution. In order to solve the problem, a fast and accurateG0distribution parameter estimation method, which combines second-kind statistics (SKS) technique with Freitas’ method of moment (MoM), is proposed. First we deduce the first and second second-kind characteristic functions ofG0distribution based on Mellin transform, and then the logarithm moments and the logarithm cumulants corresponding to the above-mentioned characteristic functions are derived; finally combined with Freitas’ method of moment, a simple iterative equation which is used for estimating theG0distribution parameters is obtained. Experimental results show that the proposed method has fast estimation speed and high fitting precision for various measured SAR image clutters with different resolutions and different number of looks.
Cauliflower‐Like Co3O4/Three‐Dimensional Graphene Composite for High Performance Supercapacitor Applications
Authors: Liu Huili , Gou Xinglong , Wang Yi , Du Xuan , Quan Can , Qi Tao
Published: September 2015

Cauliflower‐like Co3O4/three‐dimensional (3D) graphene nanocomposite material was synthesized by a facile two‐step synthesis route (heat reduction of graphite oxide (GO) and hydrothermal synthesis of Co3O4). The phase composition, morphology, and structure of the as‐obtained products were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), and X‐ray diffraction (XRD). Electrochemical properties as supercapacitor electrode materials were systematically investigated by cyclic voltammetry (CV) and constant current charge‐discharge tests. It was found that the Co3O4/3D graphene composite showed a maximum specific capacitance of 863 F g−1, which was obtained by means of CVs at a scan rate of 1 mV s−1 in 6 M KOH aqueous solution. Moreover, the composite exhibited improved cycling stability after 1,000 cycles. The good supercapacitor performance is ascribed to the combination of 3D graphene and cauliflower‐like Co3O4, which leads to a strong synergistic effect to remarkably boost the utilization ratio of Co3O4 and graphene for high capacitance.
Information Retrieval and Graph Analysis Approaches for Book Recommendation
Authors: Benkoussas Chahinez , Bellot Patrice
Published: September 2015

A combination of multiple information retrieval approaches is proposed for the purpose of book recommendation. In this paper, book recommendation is based on complex user′s query. We used different theoretical retrieval models: probabilistic as InL2 (Divergence from Randomness model) and language model and tested their interpolated combination. Graph analysis algorithms such as PageRank have been successful in Web environments. We consider the application of this algorithm in a new retrieval approach to related document network comprised of social links. We called Directed Graph of Documents (DGD) a network constructed with documents and social information provided from each one of them. Specifically, this work tackles the problem of book recommendation in the context of INEX (Initiative for the Evaluation of XML retrieval) Social Book Search track. A series of reranking experiments demonstrate that combining retrieval models yields significant improvements in terms of standard ranked retrieval metrics. These results extend the applicability of link analysis algorithms to different environments.
Impact of the AYA HOPE Comorbidity Index on Assessing Health Care Service Needs and Health Status among Adolescents and Young Adults with Cancer
Authors: Wu Xiao-Cheng , Prasad Pinki K. , Landry Ian , Harlan Linda C. , Parsons Helen M. , Lynch Charles F. , Smith Ashley W. , Hamilton Ann S. , Keegan Theresa H.M.
Published: September 2015

Background: Existing comorbidity indices were not developed for adolescent and young adults (AYA) 15 to 39 years of age. The aim of this study was to assess impact of comorbidities on health care service needs and health status among AYA cancer survivors using the newly developed AYA HOPE comorbidity index in comparison with the existing indices.

Methods: Data on comorbid conditions were obtained from medical records and service needs and health status were from a survey of AYA cancer survivors. Prevalence of comorbidities was based on the AYA HOPE index. Charlson and NCI indices were compared. Multivariable logistic regression was used.

Results: Of the 485 patients, 14.6% had ≥2 comorbidities based on the AYA HOPE Index. Prevalence of mental illness and obesity/overweight, which were not included in existing indices, were 8.2% and 5.8%, respectively. Prevalence of cardiovascular, endocrine, gastrointestinal, and neurologic conditions were higher with the AYA HOPE Index than the other two indices. Forty percent of AYA patients reported service needs, particularly for mental health services (25.2%) and support groups (17.7%). Having ≥2 comorbidities on the AYA index was associated with higher mental health service needs [OR, 2.05; 95% confidence interval (CI), 1.10–3.82] adjusting for demographic and clinical factors. Comorbidities were associated with fair/poor self-reported health status.

Conclusion: The AYA HOPE Index is a more comprehensive comorbidity index for AYA cancer patients than existing indices, and the number of comorbidities is associated with service needs and health status.

Impact: The AYA HOPE index could identify patients' additional service needs early in therapy. Cancer Epidemiol Biomarkers Prev; 24(12); 1844–9. ©2015 AACR.
Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract
Authors: Sun Yun-Yan , Peng Shiwen , Han Liping , Qiu Jin , Song Liwen , Tsai Yachea , Yang Benjamin , Roden Richard B.S. , Trimble Cornelia L. , Hung Chien-Fu , Wu T.-C.
Published: September 2015

Purpose: Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)–infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164).

Experimental Design: Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc).

Results: We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract.

Conclusions: Our results support future clinical translation using cervicovaginal TA-HPV vaccination. Clin Cancer Res; 22(3); 657–69. ©2015 AACR.

See related commentary by Nizard et al., p. 530
Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer
Authors: Purow Benjamin
Published: September 2015

Lipid kinases have largely been neglected as targets in cancer, and an increasing number of reports suggest diacylglycerol kinase alpha (DGKα) may be one with promising therapeutic potential. DGKα is one of 10 DGK family members that convert diacylglycerol (DAG) to phosphatidic acid (PA), and both DAG and PA are critical lipid second messengers in the plasma membrane. A host of important oncogenic proteins and pathways affect cancer cells in part through DGKα, including the c-Met and VEGF receptors. Others partially mediate the effects of DGKα inhibition in cancer, such as mTOR and HIF-1α. DGKα inhibition can directly impair cancer cell viability, inhibits angiogenesis, and notably may also boost T-cell activation and enhance cancer immunotherapies. Although two structurally similar inhibitors of DGKα were established decades ago, they have seen minimal in vivo usage, and it is unlikely that either of these older DGKα inhibitors will have utility for cancer. An abandoned compound that also inhibits serotonin receptors may have more translational potential as a DGKα inhibitor, but more potent and specific DGKα inhibitors are sorely needed. Other DGK family members may also provide therapeutic targets in cancer, but require further investigation. Clin Cancer Res; 21(22); 5008–12. ©2015 AACR.
A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition
Authors: Mak Milena P. , Tong Pan , Diao Lixia , Cardnell Robert J. , Gibbons Don L. , William William N. , Skoulidis Ferdinandos , Parra Edwin R. , Rodriguez-Canales Jaime , Wistuba Ignacio I. , Heymach John V. , Weinstein John N. , Coombes Kevin R. , Wang Jing , Byers Lauren Averett
Published: September 2015

Purpose: We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived in cancer cell lines. Given the contribution of tumor microenvironments to EMT, we extended our investigation of EMT to patient tumors from 11 cancer types to develop a pan-cancer EMT signature.

Experimental Design: Using the pan-cancer EMT signature, we conducted an integrated, global analysis of genomic and proteomic profiles associated with EMT across 1,934 tumors including breast, lung, colon, ovarian, and bladder cancers. Differences in outcome and in vitro drug response corresponding to expression of the pan-cancer EMT signature were also investigated.

Results: Compared with the lung cancer EMT signature, the patient-derived, pan-cancer EMT signature encompasses a set of core EMT genes that correlate even more strongly with known EMT markers across diverse tumor types and identifies differences in drug sensitivity and global molecular alterations at the DNA, RNA, and protein levels. Among those changes associated with EMT, pathway analysis revealed a strong correlation between EMT and immune activation. Further supervised analysis demonstrated high expression of immune checkpoints and other druggable immune targets, such as PD1, PD-L1, CTLA4, OX40L, and PD-L2, in tumors with the most mesenchymal EMT scores. Elevated PD-L1 protein expression in mesenchymal tumors was confirmed by IHC in an independent lung cancer cohort.

Conclusions: This new signature provides a novel, patient-based, histology-independent tool for the investigation of EMT and offers insights into potential novel therapeutic targets for mesenchymal tumors, independent of cancer type, including immune checkpoints. Clin Cancer Res; 22(3); 609–20. ©2015 AACR.
MicroRNA MIR21 and T Cells in Colorectal Cancer
Authors: Mima Kosuke , Nishihara Reiko , Nowak Jonathan A. , Kim Sun A. , Song Mingyang , Inamura Kentaro , Sukawa Yasutaka , Masuda Atsuhiro , Yang Juhong , Dou Ruoxu , Nosho Katsuhiko , Baba Hideo , Giovannucci Edward L. , Bowden Michaela , Loda Massimo , Giannakis Marios , Bass Adam J. , Dranoff Glenn , Freeman Gordon J. , Chan Andrew T. , Fuchs Charles S. , Qian Zhi Rong , Ogino Shuji
Published: September 2015

The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell–mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided α level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3+ and CD45RO+ cells (Ptrend < 0.0005). The multivariate odds ratio of the highest versus lowest quartile of MIR21 for a unit increase in quartile categories of CD3+ or CD45RO+ cells was 0.44 [95% confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26–0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell–mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer. Cancer Immunol Res; 4(1); 33–40. ©2015 AACR.
Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors
Authors: Voena Claudia , Menotti Matteo , Mastini Cristina , Di Giacomo Filomena , Longo Dario Livio , Castella Barbara , Merlo Maria Elena Boggio , Ambrogio Chiara , Wang Qi , Minero Valerio Giacomo , Poggio Teresa , Martinengo Cinzia , D'Amico Lucia , Panizza Elena , Mologni Luca , Cavallo Federica , Altruda Fiorella , Butaney Mohit , Capelletti Marzia , Inghirami Giorgio , Jänne Pasi A. , Chiarle Roberto
Published: September 2015

Non–small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKI), but the treatment is successful for only a limited amount of time; most patients experience a relapse due to the development of drug resistance. Here, we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti–PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC. Cancer Immunol Res; 3(12); 1333–43. ©2015 AACR.
A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome
Authors: Yamashita Chikara , Shigeto Hiroshi , Maeda Norihisa , Torii Takako , Ohyagi Yasumasa , Kira Jun-ichi
Published: September 2015

Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.
Bilateral Diffuse Uveal Melanocytic Proliferation: Molecular Genetic Analysis of a Case and Review of the Literature
Authors: Mittal Ruchi , Cherepanoff Svetlana , Thornton Sophie , Kalirai Helen , Damato Bertil , Coupland Sarah E.
Published: September 2015

Purpose of the Study: To describe the clinicopathological features, mutational and chromosomal copy number analysis, and 8-year follow-up of a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with clear-cell carcinoma of the endometrium. Methods: Histological evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis and GNAQ/11 mutational analysis were performed in a 67-year-old female patient with the diagnosis of BDUMP. Results: Histological evaluation revealed proliferation of bland spindle cells, diffusely replacing the uveal tract, which showed a proliferation index of less than 1%. There was absence of mutations involving the codon 209 and 183 of GNAQ, and of GNA11. MLPA analysis showed disomy 3 with polysomy 8q for both eyes. The patient died 8 years later of an unrelated condition. Conclusions: Although BDUMP is considered to be a benign proliferative disease, copy number alterations of unknown significance may occur in these lesions.
Determinants of False-Negative Fine-Needle Aspirates of Axillary Lymph Nodes in Women with Breast Cancer: Lymph Node Size, Cortical Thickness and Hilar Fat Retention
Authors: Ewing D. Eric , Layfield Lester J. , Joshi Christopher L. , Travis Mark D.
Published: September 2015

Objective: Ultrasound-guided fine-needle aspiration (UG-FNA) is utilized to sample axillary lymph nodes in breast cancer patients. Diagnostic sensitivity is good but few data exist regarding the causes of false-negative results. Study Design: Fifty-four UG-FNAs of sentinel lymph nodes with histologic follow-up were identified. Gross and radiographic lymph node size, the percentage replaced by carcinoma and the cortical thickness were correlated with false-negative rates. Results: Thirty-seven aspirates were negative, 5 of these being false-negative (9%). True-positive lymph nodes averaged 1.3 cm in dimension while false-negatives averaged 0.92 cm. Percentage involvement by carcinoma for true-positive FNAs averaged 69% while false-negatives averaged 25%. Cortical thickness averaged 5.6 mm in true-positive FNAs but 2.9 mm in false-negatives. Conclusion: A relationship exists between lymph node size and the likelihood of a false-negative FNA. Lymph nodes <1.2 cm have a higher incidence of false-negative results. Lymph nodes with <30% involvement demonstrated a higher percentage of false-negatives than those with >30% replacement. Sentinel lymph nodes <1 cm appear to be relatively poor candidates for UG-FNA. Lymph nodes with a cortical thickness <3.5 mm are more often associated with a false-negative result than nodes with a thicker cortex.