bluuebunny/crossref_metadata_2025 huggingface dataset:
The speed of object recognition from a haptic glance: event-related potential evidence
Authors: Gurtubay-Antolin Ane , Rodriguez-Herreros Borja , Rodríguez-Fornells Antoni
Published: March 2015

Recognition of an object usually involves a wide range of sensory inputs. Accumulating evidence shows that first brain responses associated with the visual discrimination of objects emerge around 150 ms, but fewer studies have been devoted to measure the first neural signature of haptic recognition. To investigate the speed of haptic processing, we recorded event-related potentials (ERPs) during a shape discrimination task without visual information. After a restricted exploratory procedure, participants ( n = 27) were instructed to judge whether the touched object corresponded to an expected object whose name had been previously presented in a screen. We encountered that any incongruence between the presented word and the shape of the object evoked a frontocentral negativity starting at ∼175 ms. With the use of source analysis and L2 minimum-norm estimation, the neural sources of this differential activity were located in higher level somatosensory areas and prefrontal regions involved in error monitoring and cognitive control. Our findings reveal that the somatosensory system is able to complete an amount of haptic processing substantial enough to trigger conflict-related responses in medial and prefrontal cortices in <200 ms. The present results show that our haptic system is a fast recognition device closely interlinked with error- and conflict-monitoring processes.
Genetic Vectors as a Tool in Association Studies: Definitions and Application for Study of Rheumatoid Arthritis
Authors: Sandalov Igor , Padyukov Leonid
Published: March 2015

To identify putative relations between different genetic factors in the human genome in the development of common complex disease, we mapped the genetic data to an ensemble of spin chains and analysed the data as a quantum system. Each SNP is considered as a spin with three states corresponding to possible genotypes. The combined genotype represents a multispin state, described by the product of individual-spin states. Each person is characterized by a single genetic vector (GV) and individuals with identical GVs comprise the GV group. This consolidation of genotypes into GVs provides integration of multiple genetic variants for a single statistical test and excludes ambiguity of biological interpretation known for allele and haplotype associations. We analyzed two independent cohorts, with 2633 rheumatoid arthritis cases and 2108 healthy controls, and data for 6 SNPs from the HTR2A locus plus shared epitope allele. We found that GVs based on selected markers are highly informative and overlap for 98.3% of the healthy population between two cohorts. Interestingly, some of the GV groups contain either only controls or only cases, thus demonstrating extreme susceptibility or protection features. By using this new approach we confirmed previously detected univariate associations and demonstrated the most efficient selection of SNPs for combined analyses for functional studies.
Unusual Blueshifting of Optical Band Gap of CdS Nanocrystals through a Chemical Bath Deposition Method
Authors: Yuan Shu Qing , Ji Peng Fei , Li Yong , Song Yue Li , Zhou Feng Qun
Published: March 2015

CdS nanocrystals are synthesized through a chemical bath deposition method. After annealing, these nanocrystals are enlarged according to Scherrer’s formula. Small nanocrystals display wide band gaps as a result of the quantum effect experienced by nanocrystals of a certain size. However, the absorption edge and green and red emissions of annealed CdS nanocrystals show obvious blueshift compared with the as-grown ones. After annealing, the intensity ratio of these green and red emissions increases, which indicated that the defect states are reduced. Therefore, the improvement in crystalline quality and the reduced strain contribute to the unusual blueshifting of the optical band gap and of the green and red emissions.
Some General Systems of Rational Difference Equations
Authors: Gelisken Ali , Kara Merve
Published: March 2015

We investigate behavior of solutions of the following systems of rational difference equations: xn+1=yn-3k-1/(±1±yn-(3k-1)xn-(2k-1)yn-(k-1)),yn+1=xn-3k-1/(±1±xn-3k-1yn-2k-1xn-k-1), where k is a positive integer and the initial conditions are real numbers. We show that every solution is periodic with 6k period, considerably improving the results in the literature.
A CADASIL-Like Case with a Novel Noncysteine Mutation of theNOTCH3Gene and Granular Deposits in the Renal Arterioles
Authors: Nakamura Kuniyuki , Ago Tetsuro , Tsuchimoto Akihiro , Noda Nozomi , Nakamura Asako , Ninomiya Toshiharu , Uchiumi Takeshi , Tsuruya Kazuhiko , Kamouchi Masahiro , Ooboshi Hiroaki , Kitazono Takanari
Published: March 2015

We herein report the finding of a 62-year-old male, who developed dysarthria and dysphagia, with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy- (CADASIL-) like cerebral lesions. He also suffered from slowly progressive renal failure with the findings of granular deposits similar to electron-dense granular osmiophilic material in the renal arterioles. We found a novel heterozygous missense mutation of theNOTCH3gene, c.4039G>C in exon 24, resulting in a p.Gly1347Arg substitution in its extracellular domain. The noncysteine substitution may underlie the pathogenesis of white matter lesions in the brain and of the chronic renal failure in the present case.
Equilibrium Analysis of a Yellow Fever Dynamical Model with Vaccination
Authors: Martorano Raimundo Silvia , Amaku Marcos , Massad Eduardo
Published: March 2015

We propose an equilibrium analysis of a dynamical model of yellow fever transmission in the presence of a vaccine. The model considers both human and vector populations. We found thresholds parameters that affect the development of the disease and the infectious status of the human population in the presence of a vaccine whose protection may wane over time. In particular, we derived a threshold vaccination rate, above which the disease would be eradicated from the human population. We show that if the mortality rate of the mosquitoes is greater than a given threshold, then the disease is naturally (without intervention) eradicated from the population. In contrast, if the mortality rate of the mosquitoes is less than that threshold, then the disease is eradicated from the populations only when the growing rate of humans is less than another threshold; otherwise, the disease is eradicated only if the reproduction number of the infection after vaccination is less than 1. When this reproduction number is greater than 1, the disease will be eradicated from the human population if the vaccination rate is greater than a given threshold; otherwise, the disease will establish itself among humans, reaching a stable endemic equilibrium. The analysis presented in this paper can be useful, both to the better understanding of the disease dynamics and also for the planning of vaccination strategies.
NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia
Authors: Gao Pan , He Fang-Fang , Tang Hui , Lei Chun-Tao , Chen Shan , Meng Xian-Fang , Su Hua , Zhang Chun
Published: March 2015

Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression ofgp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1βproduction and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversedgp91phoxoverexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN.

Erratum to “NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia”
Incidence of Alpha-Globin Gene Defect in the Lebanese Population: A Pilot Study
Authors: Farra Chantal , Daher Rose , Badra Rebecca , el Rafei Rym , Bejjany Rachelle , Charafeddine Lama , Yunis Khalid
Published: March 2015

Background. It is well established that the Mediterranean and Arab populations are at high risk for thalassemias in general and for alpha-thalassemia in particular. Yet, reports on alpha-thalassemia in Lebanon are still lacking. In this study, we aim at assessing the incidence of alpha-thalassemia in the Lebanese population.Methods. 230 newborns’ dried blood cards remaining from routine neonatal screening at the American University of Beirut Medical Center were collected for DNA extraction. Samples were screened for the 21 most commonα-globin deletions and point mutations reported worldwide, through multiplex Polymerase Chain Reaction (PCR) and Reverse-Hybridization technique.Results. Upon analyses, the carrier rate ofα-thalassemia was found to be 8%. Two mutations detected the −α3,7single gene deletion found in 75% of cases and the nongene deletionα2 IVS1 [−5nt] in the remaining samples.Conclusion. This study is the first dedicated to investigateα-thalassemia trait incidence in Lebanon. Data obtained demonstrates a high carrier rate in a relatively, highly consanguineous population; it also highlighted the presence of two common mutations. These results may be of an important impact on premarital and newborn screening policies in our country.
Virtual Goods Recommendations in Virtual Worlds
Authors: Chen Kuan-Yu , Liao Hsiu-Yu , Chen Jyun-Hung , Liu Duen-Ren
Published: March 2015

Virtual worlds (VWs) are computer‐simulated environments which allow users to create their own virtual character as an avatar. With the rapidly growing user volume in VWs, platform providers launch virtual goods in haste and stampede users to increase sales revenue. However, the rapidity of development incurs virtual unrelated items which will be difficult to remarket. It not only wastes virtual global companies’ intelligence resources, but also makes it difficult for users to find suitable virtual goods fit for their virtual home in daily virtual life. In the VWs, users decorate their houses, visit others’ homes, create families, host parties, and so forth. Users establish their social life circles through these activities. This research proposes a novel virtual goods recommendation method based on these social interactions. The contact strength and contact influence result from interactions with social neighbors and influence users’ buying intention. Our research highlights the importance of social interactions in virtual goods recommendation. The experiment’s data were retrieved from an online VW platform, and the results show that the proposed method, considering social interactions and social life circle, has better performance than existing recommendation methods.
Effect of Fiber Treatment and Fiber Loading on Mechanical Properties ofLuffa-Resorcinol Composites
Authors: Parida Chhatrapati , Dash Sarat Kumar , Das Sarat Chandra
Published: March 2015

Tensile and compressive behaviour of resorcinol-formaldehyde (RF) matrix and its composites reinforced with fibers ofLuffa cylindrica(LC) have been studied. LC fibers were subjected to chemical treatments such as alkali activation by NaOH followed by bleaching and acid hydrolysis in order to improve fiber-matrix adhesion. Both treated and untreated LC fibers are modified with calcium phosphate. The presence of hydroxy apatite, a polymorph of calcium phosphate and a major constituent of vertebrate bone and teeth, was confirmed from XRD peak of treated LC fiber. XRD analysis of the treated LC fiber has confirmed the crystalline nature of the chemically treated LC fiber by its crystallinity index. The effects of fiber loading of chemically treated and untreated LC fiber on ultimate stress, yield strength, breaking stress, and modulus of the composites were analyzed. The tensile and compressive modulus of the composites were increased with incorporation of both treated and untreated LC fibers into the RF matrix. The modulus of composites with treated LC fiber was enhanced compared to that of the untreated fiber composites. Furthermore the values of ultimate stress, yield stress, and breaking stress were increased with the incorporation of treated LC fiber in the composites.
Friction Characteristics of Machined Metal with Different Surface Morphologies
Authors: Lee Hsin-Min , Wang A-Cheng , Lin Yan-Cherng
Published: March 2015

This study examined the friction characteristics of SAE1045 medium carbon steel processed by milling machining (MM) and abrasive jet machining (AJM). Friction experiments were conducted with variations in load and friction distance. Experimental results show that micro craters produced by AJM help retain lubricant on workpiece surface and thus decrease friction coefficient. Consequently, for the same friction distance, the amount of wear on AJM test specimens is less than that of MM ones. Moreover, increase in load and surface roughness will also result in great wear on the test specimens.
Novel Mutationsin the Transcriptional Activator Domain of the Human TBX20 in Patients with Atrial Septal Defect
Authors: Monroy-Muñoz Irma Eloisa , Pérez-Hernández Nonanzit , Rodríguez-Pérez José Manuel , Muñoz-Medina José Esteban , Angeles-Martínez Javier , García-Trejo José J. , Morales-Ríos Edgar , Massó Felipe , Sandoval-Jones Juan Pablo , Cervantes-Salazar Jorge , García-Montes José Antonio , Calderón-Colmenero Juan , Vargas-Alarcón Gilberto
Published: March 2015

Background. The relevance ofTBX20gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect ofTBX20mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain.Methods. We search forTBX20mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing.Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD.Conclusions. This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.
A Balanced Power Consumption Algorithm Based on Enhanced Parallel Cat Swarm Optimization for Wireless Sensor Network
Authors: Kong Lingping , Pan Jeng-Shyang , Tsai Pei-Wei , Vaclav Snasel , Ho Jiun-Huei
Published: March 2015

The wireless sensor network (WSN) is composed of a set of sensor nodes. It is deemed suitable for deploying with large-scale in the environment for variety of applications. Recent advances in WSN have led to many new protocols specifically for reducing the power consumption of sensor nodes. A new scheme for predetermining the optimized routing path is proposed based on the enhanced parallel cat swarm optimization (EPCSO) in this paper. This is the first leading precedent that the EPCSO is employed to provide the routing scheme for the WSN. The experimental result indicates that the EPCSO is capable of generating a set of the predetermined paths and of smelting the balanced path for every sensor node to forward the interested packages. In addition, a scheme for deploying the sensor nodes based on their payload and the distance to the sink node is presented to extend the life cycle of the WSN. A simulation is given and the results obtained by the EPCSO are compared with the AODV, the LD method based on ACO, and the LD method based on CSO. The simulation results indicate that our proposed method reduces more than 35% power consumption on average.
Mobility Based Key Management Technique for Multicast Security in Mobile Ad Hoc Networks
Authors: Madhusudhanan B. , Chitra S. , Rajan C.
Published: March 2015

In MANET multicasting, forward and backward secrecy result in increased packet drop rate owing to mobility. Frequent rekeying causes large message overhead which increases energy consumption and end‐to‐end delay. Particularly, the prevailing group key management techniques cause frequent mobility and disconnections. So there is a need to design a multicast key management technique to overcome these problems. In this paper, we propose the mobility based key management technique for multicast security in MANET. Initially, the nodes are categorized according to their stability index which is estimated based on the link availability and mobility. A multicast tree is constructed such that for every weak node, there is a strong parent node. A session key‐based encryption technique is utilized to transmit a multicast data. The rekeying process is performed periodically by the initiator node. The rekeying interval is fixed depending on the node category so that this technique greatly minimizes the rekeying overhead. By simulation results, we show that our proposed approach reduces the packet drop rate and improves the data confidentiality.
A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
Authors: Chiazza Fausto , Chegaev Konstantin , Rogazzo Mara , Cutrin Juan C. , Benetti Elisa , Lazzarato Loretta , Fruttero Roberta , Collino Massimo
Published: March 2015

Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV) is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R) injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO-) donor furoxan moiety (NO-EDV). Male Wistar rats were subjected to renal ischemia (45 minutes), followed by reperfusion (6 hours). Administration of either EDV (1.2–6–30 µmol/kg, i.v.) or NO-EDV (0.3–1.2–6 µmol/kg, i.v.) dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2). NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg) was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS) and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-αoverproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.
Endocrine and Bone Complications inβ-Thalassemia Intermedia: Current Understanding and Treatment
Authors: Inati Adlette , Noureldine MohammadHassan A. , Mansour Anthony , Abbas Hussein A.
Published: March 2015

Thalassemia intermedia (TI), also known as nontransfusion dependent thalassemia (NTDT), is a type of thalassemia where affected patients do not require lifelong regular transfusions for survival but may require occasional or even frequent transfusions in certain clinical settings and for defined periods of time. NTDT encompasses three distinct clinical forms:β-thalassemia intermedia (β-TI), Hb E/β-thalassemia, andα-thalassemia intermedia (Hb H disease). Over the past decade, our understanding of the molecular features, pathophysiology, and complications of NTDT particularlyβ-TI has increased tremendously but data on optimal treatment of disease and its various complications are still lacking. In this paper, we shall review a group of commonly encountered complications inβ-TI, mainly endocrine and bone complications.
A Simulated Annealing Methodology to Multiproduct Capacitated Facility Location with Stochastic Demand
Authors: Qin Jin , Xiang Hui , Ye Yong , Ni Linglin
Published: March 2015

A stochastic multiproduct capacitated facility location problem involving a single supplier and multiple customers is investigated. Due to the stochastic demands, a reasonable amount of safety stock must be kept in the facilities to achieve suitable service levels, which results in increased inventory cost. Based on the assumption of normal distributed for all the stochastic demands, a nonlinear mixed‐integer programming model is proposed, whose objective is to minimize the total cost, including transportation cost, inventory cost, operation cost, and setup cost. A combined simulated annealing (CSA) algorithm is presented to solve the model, in which the outer layer subalgorithm optimizes the facility location decision and the inner layer subalgorithm optimizes the demand allocation based on the determined facility location decision. The results obtained with this approach shown that the CSA is a robust and practical approach for solving a multiple product problem, which generates the suboptimal facility location decision and inventory policies. Meanwhile, we also found that the transportation cost and the demand deviation have the strongest influence on the optimal decision compared to the others.
Synthesis of Binaphthyl-Based Push-Pull Chromophores with Supramolecularly Polarizable Acceptor Ends
Authors: Coluccini Carmine , Terraneo Giancarlo , Pasini Dario
Published: March 2015

We report on the design and synthesis of new enantiopure binaphthyl derivatives in which electron-donating and electron-withdrawing substituents are placed in direct conjugation, to create push-pull dyes potentially active for NLO applications. The dyes, unprecedentedly, extend theirπ-bridge from the 3,3′ positions of the binaphthyl units and incorporate as acceptors 1,3-dicarbonyl and tetrafluorobenzene units, useful for further supramolecular polarization of the chiral dyes.
Cooperation or Competition: An Evolutionary Game Study between Commercial Banks and Big Data-Based E-Commerce Financial Institutions in China
Authors: Zhao Yi , Li Dong , Pan Liqiang
Published: March 2015

On the premise of participants’ bounded rationality and information asymmetry, this paper focuses on the cooperation or competition relationship between Chinese e-commerce financial institutions and commercial banks from the perspective of dynamic game. Theoretical mathematical model is built to analyze an evolutionary stable strategy under different conditions. We adopt real-life data set collected in Alibaba’s network credit loan business case and Jingdong’s supply chain financing business case to verify the evolution process of cooperation and competition relationship. The results show that (cooperation, cooperation) is bound to be the evolutionary stable strategy (ESS) and cooperation tends to be increasingly in-depth and expansive for commercial banks as well as e-commerce financial institutions in China. The complementarity of participants’ core competitiveness is explored as the root of cooperation. Finally, strategic suggestions are put forward on cooperation between e-commerce financial institutions and commercial banks.
A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma
Authors: Ip Joseph Chok Yan , Ko Josephine Mun Yee , Yu Valen Zhuoyou , Chan Kwok Wah , Lam Alfred K. , Law Simon , Tong Daniel King Hung , Lung Maria Li
Published: March 2015

Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. Anin vivoesophageal squamous cell carcinoma (ESCC) orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and thein vivotumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.
The Use of Infrared Thermography as a Rapid, Quantitative, and Noninvasive Method for Evaluation of Inflammation Response in Different Anatomical Regions of Rats
Authors: Całkosiński Ireneusz , Dobrzyński Maciej , Rosińczuk Joanna , Dudek Krzysztof , Chrószcz Aleksander , Fita Katarzyna , Dymarek Robert
Published: March 2015

Purpose. Thermographic assessment of temperature distribution within the examined tissues allows a quick, noncontact, noninvasive measurement of their temperature. The aim of the study was to evaluate the usefulness of digital infrared imaging in monitoring experimental inflammation of pleura (PL), lower lip (LL), and left paw (LP) and right paw (RP) of lower limbs in rats. Materials and Methods. The inflammatory reaction was induced by injection of 1% carrageenin solution into pleural cavity, lip, or paws. With the use of digital infrared imaging temperature measurement was conducted at 0 to 72 hours of the inflammatory reaction. Results. The temperature decrease was observed at the site of injection directly afterwards. Next, it was gradually increasing and it reached the maximum on the third day of the inflammatory reaction. Statistically significant changes were observed after 48-hour period in PL and LL regions, as well as after 72-hour period in LP and RP regions P<0.005. Conclusion. It was found that thermographic examination allows for indicating the presence of inflammatory reaction within examined tissues and determining the dynamics of this process. This method could be used as alternative procedure that allows using fewer animals for experiments.
NRF2 Pathway Activation and Adjuvant Chemotherapy Benefit in Lung Squamous Cell Carcinoma
Authors: Cescon David W. , She Desmond , Sakashita Shingo , Zhu Chang-Qi , Pintilie Melania , Shepherd Frances A. , Tsao Ming-Sound
Published: March 2015

Purpose: Genomic profiling of lung squamous cell carcinomas (SCC) has identified NRF2 pathway alterations, which activate oxidative response pathways, in one third of tumors. Preclinical data suggest these tumors may be resistant to platinum-based chemotherapy. We evaluated the clinical relevance of these findings and assessed whether NRF2 activation predicts benefit from adjuvant chemotherapy in SCC.

Experimental Design: Logistic regression (LR) and significance analysis of microarrays (SAM) were applied to all 104 TCGA (The Cancer Genome Atlas) SCC cases that had microarray gene expression and mutation data to identify genes associated with somatic NRF2 pathway alterations. The resulting signature (NRF2ACT) was tested in 3 independent SCC datasets to evaluate its prognostic and predictive effects. IHC and sequencing for NRF2 and KEAP1 were evaluated in one cohort (n = 43) to assess the relationship between gene expression, mutational status, and protein expression.

Results: Twenty-eight genes were identified by overlap between LR (291 genes) and SAM (30 genes), and these consistently separated SCC into 2 groups in all datasets, corresponding to putatively NRF pathway–activated and wild-type (WT) tumors. NRF2ACT was not prognostic. However, improved survival with adjuvant chemotherapy in the JBR.10-randomized trial appears limited to patients with the WT signature (HR 0.32, P = 0.16; NRF2ACT HR 2.28, P = 0.48; interaction P = 0.15). NRF2ACT was highly correlated with mutations in NRF2 and KEAP1, and with high NRF2 protein expression.

Conclusions: A gene expression signature of NRF2 pathway activation is associated with benefit from adjuvant cisplatin/vinorelbine in SCC. Patients with NRF2 pathway–activating somatic alterations may have reduced benefit from this therapy. Clin Cancer Res; 21(11); 2499–505. ©2015 AACR.
Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300
Authors: Uttarkar Sagar , Dukare Sandeep , Bopp Bertan , Goblirsch Michael , Jose Joachim , Klempnauer Karl-Heinz
Published: March 2015

The transcription factor c-Myb is highly expressed in hematopoietic progenitor cells and controls the transcription of genes important for lineage determination, cell proliferation, and differentiation. Deregulation of c-Myb has been implicated in the development of leukemia and certain other types of human cancer. c-Myb activity is highly dependent on the interaction of the c-Myb with the KIX domain of the coactivator p300, making the disruption of this interaction a reasonable strategy for the development of Myb inhibitors. Here, we have used bacterial Autodisplay to develop an in vitro binding assay that mimics the interaction of Myb and the KIX domain of p300. We have used this binding assay to investigate the potential of Naphthol AS-E phosphate, a compound known to bind to the KIX domain, to disrupt the interaction between Myb and p300. Our data show that Naphthol AS-E phosphate interferes with the Myb–KIX interaction in vitro and inhibits Myb activity in vivo. By using several human leukemia cell lines, we demonstrate that Naphthol AS-E phosphate suppresses the expression of Myb target genes and induces myeloid differentiation and apoptosis. Our work identifies Naphthol AS-E phosphate as the first low molecular weight compound that inhibits Myb activity by disrupting its interaction with p300, and suggests that inhibition of the Myb–KIX interaction might be a useful strategy for the treatment of leukemia and other tumors caused by deregulated c-Myb. Mol Cancer Ther; 14(6); 1276–85. ©2015 AACR.

See related commentary by Liu et al., p. 1273
Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells
Authors: Liu Shin-Yun , Jeng Jaan-Yeh , Lin Han-Chen , Hung Kuan-Yu , Lai I-Rue
Published: March 2015

Background: Peritoneal lavage after cancer surgery is performed to reduce microscopic residual tumors in the peritoneum. This study evaluated the effects and mechanism of dialysate lavage in reducing the peritoneal implantation of gastric cancer cells. Methods: Gastric cancer cells (MKN45 or AGS) were cultured with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in vitro cell susceptibility to dialysate, including cell proliferation, cell death, cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A murine model for gastric cancer cell peritoneal seeding was established to test the effects of PD and NS lavage on animal survival and tumor growth. Results: A significant decrease in cell proliferation in PD and NS (75.2 ± 0.1 vs. 12.4 ± 0.2% in MKN45, p = 0.009; 58.2 ± 0.01 vs. 28.0 ± 0.01% in AGS, p = 0.008), an increase in mitochondrial permeability transition (93.0 ± 2.6 vs. 18.0 ± 2.9% in MKN45, p = 0.021; 86.8 ± 4.6 vs. 47.7 ± 10.2% in AGS, p < 0.001), and an increase in the expression of cleaved PARP and increased death (25.6 ± 9.4 vs. 16.9 ± 5.3% in MKN45, p = 0.031; 39.5 ± 5.1 vs. 20.9 ± 3.9% in AGS, p = 0.008) were recorded for gastric cancer cells separately exposed to PD and NS. Twenty-four days after inoculating MKN45 cells (5 × 106/0.1 ml) in the peritoneal cavity, the average number of seeded tumors was 67.3 ± 10.8, 92.3 ± 6.0, and 29.2 ± 16.7 (p = 0.032), and the total weight of tumors was 0.98 ± 0.21, 0.58 ± 0.12, and 0.31 ± 0.17 g (p = 0.008), respectively, for mice receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for the PD lavage group was 22% compared to 0% for the sham injection and NS lavage groups (p = 0.034). Conclusion: PD induced significant cytotoxicity in gastric cancer cells that was related to mitochondrial perturbation. The use of PD lavage was effective in reducing the peritoneal implantation of gastric cancers in a murine model.
Establishment of Population-Based Stroke Registry in Ludhiana City, Northwest India: Feasibility and Methodology
Authors: Pandian Jeyaraj Durai , Singh Gagandeep , Bansal Rajinder , Paul Birinder S. , Singla Monika , Singh Shavinder , Verma Shweta J. , Moodbidri Premjeeth , Kaur Paramdeep , Mehmi Gagandeep , Arora Om P. , Dhanuka Arun K. , Sharma Meenakshi ,   Collaborators and the Indian Council of Medical Research Task Force Group
Published: March 2015

Background/Aims: The Indian Council of Medical Research (ICMR) initiated the Task Force Project to evaluate the feasibility of conducting a population-based stroke registry in Ludhiana city, Punjab, Northwest India. Methods: All first-ever, stroke patients over 18 years from the city of Ludhiana were included in the study from March 26th 2010 to March 25th 2011. Stroke information was collected based on the WHO STEPS approach from the participating hospitals, scan centres and doctors. Modified Rankin Scale (mRS) was administered by telephonic interview at 28 days after stroke. The information on stroke deaths was obtained from the Municipal Corporation (MC) office. Results: A total of 905 first-ever stroke patients were documented. After excluding duplicate cases and patients from outside the city, 493 patients were included. The practical issues identified in data collection from these centres were reluctance to take informed consent, lack of willingness to share the data, difficulty to identify key persons from each centre, retrieving medical records from public hospitals and poor documentation of deaths in MC office. Conclusion: Population-based stroke registry was feasible in an urban population with the above methodology. The issues related to feasibility were identified and necessary changes were made for the main phase of the registry.
The Use of Antidepressant Medication before and after the Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Cohort Study
Authors: Pisa Federica Edith , Logroscino Giancarlo , Casetta Anica , Cecotti Laura , Verriello Lorenzo , Bratina Alessio , Sartori Arianna , Lazzarino de Lorenzo Lucio , Eleopra Roberto , Barbone Fabio
Published: March 2015

Background: The prevalent use of antidepressants (ATDs) in patients with Amyotrophic Lateral Sclerosis (ALS) varies across cross-sectional and clinic-based published studies. This population-based cohort study assesses the real-world prevalence of the use of ATDs, its trajectory and the association of incident use with clinical characteristics. Methods: All patients with incident ALS in the Friuli Venezia Giulia region, Italy, from 2002 to 2009, were identified through multiple sources including health databases. Diagnosis was validated through clinical documentation review. ATDs prescriptions from 2000 to 2011 were obtained from regional database. The trajectory was estimated through generalized estimating equations for repeated measures logistic regression and the Hazard ratio (HR) of initiating ATDs through multivariate proportional hazard Cox regression. Results: In this cohort of 261 ALS cases, age-, sex-adjusted prevalence of the use of ATDs was 37.3%, higher than in general population. The trajectory increased by 16% in 1-year period across diagnosis. Age ≤67 years at diagnosis (HR 1.28, 95% CI 0.84-1.95) and bulbar onset (1.43, 95% CI 0.90-2.26) were positively associated with initiating ATDs after diagnosis. Conclusions: More than one-third of patients used ATDs. Depression may occur more frequently than previously reported. Depression may precede motor alterations and be related to both ALS diagnosis and progression.
Laser Therapy for Bladder Outlet Obstruction: A Prospective Analysis of All Patients Receiving Treatment with the GreenLight XPS 180-Watt Laser System after Introduction at a Single Center
Authors: Tietze Stefan , Kiehle Beatrix , Krause Jens , Behrendt Wolf , Hamza Amir
Published: March 2015

Objective: The objective was to assess and publish our first experiences with the GreenLight XPS™ 180-watt laser in men suffering from bladder outlet obstruction. Patients and Methods: From January 2013 to February 2014, the results of 142 patients were analyzed prospectively at a single center. Indications for disobstruction were in line with current EAU guidelines, but independent of the underlying causes of obstruction. Assessments were made of the prostate size, International Prostate Symptom Score (IPSS), postvoid residual (PVR) and maximum urinary flow (Qmax). Intraoperative data such as lasing time, surgery time, applied energy and blood transfusions were recorded. Reinterventions and complications were evaluated. Results: The average prostate volume was 29.6 ml (2-82). The average surgery time was 50 min (13-157). Qmax increased by an average of 20.2 ml/s (p < 0.05). On average, PVR was reduced by 162 ml (p < 0.05). Conclusion: The GreenLight XPS™ 180-watt laser is an effective treatment option for bladder outlet obstruction with a low perioperative complications rate, and it shows results comparable with transurethral resection of the prostate. Even multimorbid patients and patients with long-term catheter requirements may be treated due to its high safety profile and reliable results.
Elevated Erythropoietin and Multicystic Neoplasm of the Pancreas
Authors: Nai Qiang , Regeti Kalyani , Arshed Sabrina , Hossain Mohammed Amzad , Zhang Ping , Luo Hongxiu , Singh Shilpi , Mathew Teena , Islam Mohammed , Sen Shuvendu , Yousif Abdalla M. , Duhl Jozsef
Published: March 2015

Cystic lesions of the pancreas are more frequently recognized due to the widespread use of improved imaging techniques. There are a variety of pancreatic cystic lesions with different clinical presentations and malignant potentials, and their management depends on the type of the cysts. Although the early recognition of a cystic neoplasm with malignant potential provides an opportunity of early surgical treatment, the precise diagnosis of the cystic neoplasm can be a challenge, largely due to the lack of reliable biomarkers of malignant transformation. We report a case of a large, multicystic neoplasm within the body and tail of the pancreas complicated by elevated erythropoietin, which is likely related to the malignant transformation of the pancreatic neoplasm.
Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation
Authors: Nordling Sofia , Hong Jaan , Fromell Karin , Edin Fredrik , Brännström Johan , Larsson Rolf , Nilsson Bo , U. Magnusson Peetra
Published: March 2015

Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vasculature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.
Relationship Between Sinus Rhythm Late Activation Zones and Critical Sites for Scar-Related Ventricular Tachycardia
Authors: Irie Tadanobu , Yu Ricky , Bradfield Jason S. , Vaseghi Marmar , Buch Eric F. , Ajijola Olujimi , Macias Carlos , Fujimura Osamu , Mandapati Ravi , Boyle Noel G. , Shivkumar Kalyanam , Tung Roderick
Published: March 2015

Background—

It is not known whether the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits.

Methods and Results—

Isochronal late activation maps were constructed to display ventricular activation during sinus rhythm over 8 isochrones. Analysis was performed at successful VT termination sites and prospectively tested. Thirty-three patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those who underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5%–100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1-cm radius. Ten consecutive patients underwent ablation prospectively guided by isochronal late activation maps, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone.

Conclusions—

Late potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification.
Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice
Authors: Grandoch Maria , Feldmann Kathrin , Göthert Joachim R. , Dick Lena S. , Homann Susanne , Klatt Christina , Bayer Julia K. , Waldheim Jan N. , Rabausch Berit , Nagy Nadine , Oberhuber Alexander , Deenen René , Köhrer Karl , Lehr Stefan , Homey Bernhard , Pfeffer Klaus , Fischer Jens W.
Published: March 2015

Rationale:

Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear.

Objective:

The aim of this study was to elucidate the role of LTbR in atherosclerosis.

Methods and Results:

After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE
−/−
/LTbR
−/−
) exhibited lower aortic plaque burden than did apoE
−/−
littermates. Macrophage content at the aortic root and in the aorta was reduced, as determined by immunohistochemistry and flow cytometry. In line with a decrease in plaque inflammation, chemokine (C–C motif) ligand 5 (
Ccl5
) and other chemokines were transcriptionally downregulated in aortic tissue from apoE
−/−
/LTbR
−/−
mice. Moreover, bone marrow chimeras demonstrated that LTbR deficiency in hematopoietic cells mediated the atheroprotection. Furthermore, during atheroprogression, apoE
−/−
mice exhibited increased concentrations of cytokines, for example, Ccl5, whereas apoE
−/−
/LTbR
−/−
mice did not. Despite this decreased plaque macrophage content, flow cytometric analysis showed that the numbers of circulating lymphocyte antigen 6C (Ly6C)
low
monocytes were markedly elevated in apoE
−/−
/LTbR
−/−
mice. The influx of these cells into atherosclerotic lesions was significantly reduced, whereas apoptosis and macrophage proliferation in atherosclerotic lesions were unaffected. Gene array analysis pointed to chemokine (C–C motif) receptor 5 as the most regulated pathway in isolated CD115
+
cells in apoE
−/−
/LTbR
−/−
mice. Furthermore, stimulating monocytes from apoE
−/−
mice with agonistic anti-LTbR antibody or the natural ligand lymphotoxin-α1β2, increased
Ccl5
mRNA expression.

Conclusions:

These findings suggest that LTbR plays a role in macrophage-driven inflammation in atherosclerotic lesions, probably by augmenting the Ccl5-mediated recruitment of monocytes.
Egocentric Perspective: Depicting the Body from Its Own Point of View
Authors: Pepperell Robert
Published: March 2015

We are almost always visible to ourselves. Depending on how you are seated, reclining or standing, you will see parts of your nose, legs, hands, arms, shoulders or trunk from your own point of view. Yet these everyday features of our visual world are rarely depicted—and hardly ever in a way that accords with our perceptual experience. This paper will consider why we tend to ignore this “egocentric perspective” and how it can be represented.
Facilitating Creative Equality in Art-Science: A Methodological
Experiment
Authors: Wienroth Matthias , Goldschmidt Pippa
Published: March 2015

In this article the authors discuss facilitation as a way to develop creative equality in art-science based on their experiences working on an art-science project. They suggest that the space in which representatives from the domains of sciences and arts come together to collaborate is a trading zone in which novel links and relationships can be created. They introduce the notion of “boundary method” to describe facilitation as a method that can endure different meaning-making strategies and meanings employed by stakeholders yet still retain its utility for encouraging creativity at a cross-disciplinary interface rather than within a dominant discipline.
Redescription of Coronoquadroppia monstruosa (Hammer, 1979) (Acari, Oribatida, Quadroppiidae) from Java and variability of the species in Europe
Authors: WEIGMANN GERD , SCHATZ HEINRICH
Published: March 2015

A main goal of this study was the comparison of type material of Coronoquadroppia monstruosa (Hammer, 1979) from Java with European populations which were supposed by authors to be conspecific. The species identity of most respective European findings with a type specimen can be confirmed. Yet within some populations from Germany, Austria and northern Italy, specimens with morphological variations are present, resembling partly C. gumista (Gordeeva et Tarba, 1990) from the Caucasus in regard of a transversal band in the rostral structure. This and other described modifications are supposed to be individual variability within the species C. monstruosa. A detailed morphological analysis is presented, resulting in the division of the Quadroppia complex into the genera Quadroppia and Coronoquadroppia as first proposed by Ohkubo (1995).