bluuebunny/crossref_metadata_2025 huggingface dataset:
ESR1 Amplification is Rare in Breast Cancer and is Associated with High Grade and High Proliferation: A Multiplex Ligation-Dependent Probe Amplification Study
Authors: Moelans Cathy B. , Monsuur Hanneke N. , de Pinth Johannes H. , Radersma Remco D. , de Weger Roel A. , van Diest Paul J.
Published: January 2015

Background: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα can be caused by estrogen receptor 1 (ESR1) gene amplification and was originally reported to be a frequent event associated with a significantly longer survival for ER-positive women treated with adjuvant tamoxifen monotherapy, which was however questioned by subsequent studies.

Methods: This study aimed to reanalyze the frequency of ESR1 amplification by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH), and to assess clinicopathologic correlations. MLPA was performed in a group of 135 breast cancer patients, and gains/amplifications were subjected to FISH.

Results: True ESR1 amplification by MLPA was rare (2%) and only 6% more patients showed a modest gain of ESR1. All MLPA-detected ESR1 amplifications and nearly all ESR1 gains were also FISH amplified and gained, but not all FISH amplifications/gains were MLPA amplified/gained, leading to an overall concordance of only 60% between both techniques. All 3 MLPA and FISH ESR1 amplified cases had high ERα expression, but there was no obvious correlation between ESR1 gain and ER status by IHC. ESR1 gains/amplifications were not associated with HER2 gain/amplification, but seemed to be associated with older age. Surprisingly, ESR1 gain/amplification was not associated with low grade as reported previously, but correlated with high grade and high proliferation. Furthermore, ESR1 gain/amplification by MLPA was not associated with nodal status or tumor size (pT status).

Conclusion: ESR1 amplification as detected by MLPA is rare in breast cancer, and seems to be associated with high ERα expression, high age, high grade and high proliferation. This study confirms previous studies that showed differences in the ESR1 amplification frequencies detected by different techniques.
Optimizing UPC Programs for Multi-Core Systems
Authors: Zheng Yili
Published: January 2015

The Partitioned Global Address Space (PGAS) model of Unified Parallel C (UPC) can help users express and manage application data locality on non-uniform memory access (NUMA) multi-core shared-memory systems to get good performance. First, we describe several UPC program optimization techniques that are important to achieving good performance on NUMA multi-core computers with examples and quantitative performance results. Second, we use two numerical computing kernels, parallel matrix–matrix multiplication and parallel 3-D FFT, to demonstrate the end-to-end development and optimization for UPC applications. Our results show that the optimized UPC programs achieve very good and scalable performance on current multi-core systems and can even outperform vendor-optimized libraries in some cases.
Sensor Relocation for Emergent Data Acquisition in Sparse Mobile Sensor Networks
Authors: Wu Wei , Li Xiaohui , Xiang Shili , Lim Hock Beng , Tan Kian-Lee
Published: January 2015

In this paper, we study the problem of sensor relocation for emergent data acquisition (initiated by a base station) in sparse mobile sensor networks. We propose a distributed scheme called BRIDGE that relocates mobile sensors to fulfill an emergent data acquisition task with the objective to minimize the task completion time. BRIDGE gradually finds a sensor that is close to the task location and relocates that sensor to the task location, and at the same time relocates some other sensors to connect that sensor to the base station. BRIDGE exploits the encountered sensors during relocation, and handles the challenges caused by intermittent connections. Our extensive performance study shows the effectiveness of our proposed scheme.
The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival
Authors: Antonacopoulou Anna G. , Floratou Konstantina , Bravou Vasiliki , Kottorou Anastasia , Dimitrakopoulos Fotinos-Ioannis , Marousi Stella , Stavropoulos Michalis , Koutras Agelos K. , Scopa Chrisoula D. , Kalofonos Haralabos P.
Published: January 2015

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.

Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.

Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.

Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.
Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type
Authors: Costa Ana Flávia , Altemani Albina , Vékony Hedy , Bloemena Elisabeth , Fresno Florentino , Suárez Carlos , Llorente José Luis , Hermsen Mario
Published: January 2015

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.

Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.

Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.

Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.
A Programming Model Performance Study Using the NAS Parallel Benchmarks
Authors: Shan Hongzhang , Blagojević Filip , Min Seung-Jai , Hargrove Paul , Jin Haoqiang , Fuerlinger Karl , Koniges Alice , Wright Nicholas J.
Published: January 2015

Harnessing the power of multicore platforms is challenging due to the additional levels of parallelism present. In this paper we use the NAS Parallel Benchmarks to study three programming models, MPI, OpenMP and PGAS to understand their performance and memory usage characteristics on current multicore architectures. To understand these characteristics we use the Integrated Performance Monitoring tool and other ways to measure communication versus computation time, as well as the fraction of the run time spent in OpenMP. The benchmarks are run on two different Cray XT5 systems and an Infiniband cluster. Our results show that in general the three programming models exhibit very similar performance characteristics. In a few cases, OpenMP is significantly faster because it explicitly avoids communication. For these particular cases, we were able to re-write the UPC versions and achieve equal performance to OpenMP. Using OpenMP was also the most advantageous in terms of memory usage. Also we compare performance differences between the two Cray systems, which have quad-core and hex-core processors. We show that at scale the performance is almost always slower on the hex-core system because of increased contention for network resources.
Recovery of Flash Memories for Reliable Mobile Storages
Authors: Moon Daesung , Park Byungkwan , Chung Yongwha , Park Jin-Won
Published: January 2015

As the mobile appliance is applied to many ubiquitous services and the importance of the information stored in it is increased, the security issue to protect the information becomes one of the major concerns. However, most previous researches focused only on the communication security, not the storage security. Especially, a flash memory whose operational characteristics are different from those of HDD is used increasingly as a storage device for the mobile appliance because of its resistance to physical shock and lower power requirement. In this paper, we propose a flash memory management scheme targeted for guaranteeing the data integrity of the mobile storage. By maintaining the old data specified during the recovery window, we can recover the old data when the mobile appliance is attacked. Also, to reduce the storage requirement for the recovery, we restrict the number of versions to be copied, called Degree of Integrity (DoI). Especially, we consider both the reclaim efficiency and the wear leveling which is a unique characteristic of the flash memory. Based on the performance evaluation, we confirm that the proposed scheme can be acceptable to many applications as a flash memory management scheme for improving data integrity.
An Enhanced MPR-Based Solution for Flooding of Broadcast Messages in OLSR Wireless ad hoc Networks
Authors: Lin Tzu-Hua , Chao Han-Chieh , Woungang Isaac
Published: January 2015

In an Optimized Link State Routing (OLSR)-based mobile wireless network, optimizing the flooding of broadcast messages is a challenging task due to node's mobility and bandwidth resource consumption. To complement existing solutions to this problem, the Multi-Point Relays (MPR) selection has recently been advocated as a promising technique that has an additional feature of reducing the number of redundant re-transmission occurring in the network. This paper continuous on the investigation of an existing MPR-based solution, arguing that by considering a cost factor as an additional decision parameter in selecting the MPR nodes, the enhanced MPR selection algorithm leads to less packet loss in the network. Simulation experiments are presented to validate the stated goal, using the average packet loss ratio as the performance metric.
Molecular Differences between Ductal CarcinomaIn Situand Adjacent Invasive Breast Carcinoma: A Multiplex Ligation-Dependent Probe Amplification Study
Authors: Moelans Cathy B. , de Weger Roel A. , Monsuur Hanneke N. , Maes Anoek H. J. , van Diest Paul J.
Published: January 2015

Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown. In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.

There were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p=0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high-grade IDC was similar, and although EGFR alterations were exclusively found in high-grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.

In conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high-grade DCIS showed more copy number changes than low/intermediate-grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high-grade DCIS specific genes may be potential targets for treatment and/or predict progression.
A Protocol for Content-Based Communication in Disconnected Mobile Ad Hoc Networks
Authors: Haillot Julien , Guidec Frédéric
Published: January 2015

In content-based communication, information flows towards interested hosts rather than towards specifically set destinations. This new style of communication perfectly fits the needs of applications dedicated to information sharing, news distribution, service advertisement and discovery, etc. In this paper we address the problem of supporting content-based communication in partially or intermittently connected mobile ad hoc networks (MANETs). The protocol we designed leverages on the concepts of opportunistic networking and delay-tolerant networking in order to account for the absence of end-to-end connectivity in disconnected MANETs. The paper provides an overview of the protocol, as well as simulation results that show how this protocol can perform in realistic conditions.
Energy Efficient Resource Management in Mobile Grid
Authors: Li Chunlin , Li Layuan
Published: January 2015

Energy efficient computing has recently become hot research area. Many works have been carried out on conserving energy, but considering energy efficiency in grid computing is few. This paper proposes energy efficient resource management in mobile grid. The objective of energy efficient resource management in mobile grid is to maximize the utility of the mobile grid which is denoted as the sum of grid application utility. The utility function models benefits of application and system. By using nonlinear optimization theory, energy efficient resource management in mobile grid can be formulated as multi objective optimization problem. In order to derive a distributed algorithm to solve global optimization problem in mobile grid, we decompose the problem into the sub problems. The proposed energy efficient resource management algorithm decomposes the optimization problem via iterative method. To test the performance of the proposed algorithm, the simulations are conducted to compare proposed energy efficient resource management algorithm with other energy aware scheduling algorithm.
Global Consistency Management Methods Based on Escrow Approaches in Mobile ad Hoc Networks
Authors: Hara Takahiro , Nishio Shojiro
Published: January 2015

In a mobile ad hoc network, consistency management of data operations on replicas is a crucial issue for system performance. In our previous work, we classified several primitive consistency levels according to the requirements from applications and provided protocols to realize them. In this paper, we assume special types of applications in which the instances of each data item can be partitioned and propose two consistency management protocols which are combinations of an escrow method and our previously proposed protocols. We also report simulation results to investigate the characteristics of these protocols in a mobile ad hoc network. From the simulation results, we confirm that the protocols proposed in this paper drastically improve data availability and reduce the traffic for data operations while maintaining the global consistency in the entire network.
Dual Effects ofβ3Integrin Subunit Expression on Human Pancreatic Cancer Models
Authors: Marchán S. , Pérez-Torras S. , Vidal A. , Adan J. , Mitjans F. , Carbó N. , Mazo A.
Published: January 2015

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.

Methods: In view of these findings, we examined the role ofβ3in pancreatic cancer by generating two stableβ3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.

Results: Transduction ofβ3selectively augmented the functional membraneαvβ3integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected inβ3-overexpressing cells. Moreover, tumors expressingβ3displayed reduced growth. Interestingly, treatment of mice with anαv-blocking antibody inhibited the growth ofβ3-expressing tumors to a higher extent.

Conclusion: Our results collectively support the hypothesis thatαvβ3integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.
Using Mobile Devices to Support Online Collaborative Learning
Authors: Caballé Santi , Xhafa Fatos , Barolli Leonard
Published: January 2015

Mobile collaborative learning is considered the next step of on-line collaborative learning by incorporating mobility as a key and breakthrough requirement. Indeed, the current wide spread of mobile devices and wireless technologies brings an enormous potential to e-learning, in terms of ubiquity, pervasiveness, personalization, flexibility, and so on. For this reason, Mobile Computer-Supported Collaborative Learning has recently grown from a minor research field to significant research projects covering a fairly variety of formal and specially informal learning settings, from schools and universities to workplaces, museums, cities and rural areas. Much of this research has shown how mobile technology can offer new opportunities for groups of learners to collaborate inside and beyond the traditional instructor-oriented educational paradigm. However, mobile technologies, when specifically applied to collaborative learning activities, are still in its infancy and many challenges arise. In addition, current research in this domain points to highly specialized study cases, uses, and experiences in specific educational settings and thus the issues addressed in the literature are found dispersed and disconnected from each other. To this end, this paper attempts to bridge relevant aspects of mobile technologies in support for collaborative learning and provides a tighter view by means of a multidimensional approach.
Overlapping Communication with Computation Using OpenMP Tasks on the GTS Magnetic Fusion Code
Authors: Preissl Robert , Koniges Alice , Ethier Stephan , Wang Weixing , Wichmann Nathan
Published: January 2015

Application codes in a variety of areas are being updated for performance on the latest architectures. In this paper we examine an application, which comes from magnetic fusion for performance acceleration with a particular emphasis on methods that are applicable for many/multicore and future architectural designs. We take an important magnetic fusion particle code that already includes several levels of parallelism including hybrid MPI combined with OpenMP. We study how to include new advanced hybrid models, which extend the applicability of OpenMP tasks and exploit multi-threaded MPI support to overlap communication and computation. Experiments carried out on Cray XT4 and XT5 machines resulting in a speed-up of up to 35% of the investigated GTS particle shifter kernel show the benefits and applicability of this approach.
Balanced Bipartite Graph Based Register Allocation for Network Processors in Mobile and Wireless Networks
Authors: Tang Feilong , You Ilsun , Guo Minyi , Guo Song , Zheng Long
Published: January 2015

Mobile and wireless networks are the integrant infrastructure of mobile and pervasive computing that aims at providing transparent and preferred information and services for people anytime anywhere. In such environments, end-to-end network bandwidth is crucial to improve user's transparent experience when providing on-demand services such as mobile video playing. As a result, powerful computing power is required for networked nodes, especially for routers. General-purpose processors cannot meet such requirements due to their limited processing ability, and poor programmability and scalability. Intel's network processor IXP is specially designed for fast packet processing to achieve a broad bandwidth. IXP provides a large number of registers to reduce the number of memory accesses. Registers in an IXP are physically partitioned as two banks so that two source operands in an instruction have to come from the two banks respectively, which makes the IXP register allocation tricky and different from conventional ones. In this paper, we investigate an approach for efficiently generating balanced bipartite graph and register allocation algorithms for the dual-bank register allocation in IXPs. The paper presents a graph uniform 2-way partition algorithm (FPT), which provides an optimal solution to the graph partition, and a heuristic algorithm for generating balanced bipartite graph. Finally, we design a framework for IXP register allocation. Experimental results demonstrate the framework and the algorithms are efficient in register allocation for IXP network processors.
Enhancing MISP with Fast Mobile IPv6 Security
Authors: You Ilsun , Lee Jong-Hyouk , Hori Yoshiaki , Sakurai Kouichi
Published: January 2015

The Mobile Broadband Association has developed the MIS and MISAUTH protocols as link-layer fast authentication protocols. A combination of MIS and MISAUTH protocols, called as MISP, provides secure and fast connection for a wireless access network, but it has been reported that MISP creates a weak session key and suffers from a denial-of-service attack. In addition, a transaction with an authentication server that is required for every authentication is considered as a delay factor during handovers. In this paper, we present an improvement of MISP that utilizes the fast handover approach of Fast Mobile IPv6 and minimizes an involvement of the authentication server while eliminating identified security drawbacks of MISP. The formal security analysis is performed to verify the correctness of the proposed scheme. Moreover, the handover performance of the proposed scheme is compared with an existing scheme.
Optical and Digital Microscopic Imaging Techniques and Applications in Pathology
Authors: Chen Xiaodong , Zheng Bin , Liu Hong
Published: January 2015

The conventional optical microscope has been the primary tool in assisting pathological examinations. The modern digital pathology combines the power of microscopy, electronic detection, and computerized analysis. It enables cellular-, molecular-, and genetic-imaging at high efficiency and accuracy to facilitate clinical screening and diagnosis. This paper first reviews the fundamental concepts of microscopic imaging and introduces the technical features and associated clinical applications of optical microscopes, electron microscopes, scanning tunnel microscopes, and fluorescence microscopes. The interface of microscopy with digital image acquisition methods is discussed. The recent developments and future perspectives of contemporary microscopic imaging techniques such as three-dimensional and in vivo imaging are analyzed for their clinical potentials.
Book Review
Authors: Brown Adrian
Published: January 2015

“Numerical Methods for Special Functions” by Gil, Seguar and Temme is a collection of methods and approaches for finding the most efficient and accurate ways of computing values of functions that have no general definition. “Numerical Methods for Special Functions” might appear at first glance to be a boring and perhaps dry subject for non-mathematicians, and indeed it is a little difficult to approach without being an expert in the area, but if you do find yourself in need of some hints for the best implementations available, this book might be a life saver.
Differential Signature of the Centrosomal MARK4 Isoforms in Glioma
Authors: Magnani Ivana , Novielli Chiara , Fontana Laura , Tabano Silvia , Rovina Davide , Moroni Ramona F. , Bauer Dario , Mazzoleni Stefania , Colombo Elisa A. , Tedeschi Gabriella , Monti Laura , Porta Giovanni , Bosari Silvano , Frassoni Carolina , Galli Rossella , Bello Lorenzo , Larizza Lidia
Published: January 2015

Background: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs) and mouse neural stem cells (NSCs) by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker.
Semantic File Annotation and Retrieval on Mobile Devices
Authors: Jan Sadaqat , Li Maozhen , Al-Sultany Ghaidaa , Al-Raweshidy Hamed , Shah Ibrar Ali
Published: January 2015

The rapid development of mobile technologies has facilitated users to generate and store files on mobile devices such as mobile phones and PDAs. However, it has become a challenging issue for users to efficiently and effectively search for files of interest in a mobile environment involving a large number of mobile nodes. This paper presents SemFARM framework which facilitates users to publish, annotate and retrieve files which are geographically distributed in a mobile network enabled by Bluetooth. The SemFARM framework is built on semantic web technologies in support of file retrieval on low-end mobile devices. A generic ontology is developed which defines a number of keywords, their possible domains and properties. Based on semantic reasoning, similarity degrees are computed to match user queries with published file descriptions. The SemFARM prototype is implemented using the Java mobile platform (J2ME). The performance of SemFARM is evaluated from a number of aspects in comparison with traditional mobile file systems and enhanced alternatives. Experimental results are encouraging showing the effectiveness of SemFARM in file retrieval. We can conclude that the use of semantic web technologies have facilitated file retrieval in mobile computing environments maximizing user satisfaction in searching for files of interest.
Intra-tumoral Heterogeneity ofKRASandBRAFMutation Status in Patients with Advanced Colorectal Cancer (aCRC) and Cost-Effectiveness of Multiple Sample Testing
Authors: Richman Susan D. , Chambers Philip , Seymour Matthew T. , Daly Catherine , Grant Sophie , Hemmings Gemma , Quirke Philip
Published: January 2015

KRAS mutation status is established as a predictive biomarker of benefit from anti-EGFr therapies. Mutations are normally assessed using DNA extracted from one formalin-fixed, paraffin-embedded (FFPE) tumor block. We assessed heterogeneity of KRAS and BRAF mutation status intra-tumorally (multiple blocks from the same primary tumor). We also investigated the utility and efficiency of genotyping a ‘DNA cocktail’ prepared from multiple blocks. We studied 68 consenting patients in two randomized clinical trials. DNA was extracted, from ≥2 primary tumor FFPE blocks per patient. DNA was genotyped by pyrosequencing for KRAS codons 12, 13 and 61 and BRAF codon 600. In patients with heterogeneous mutation status, DNA cocktails were prepared and genotyped. Among 69 primary tumors in 68 patients, 7 (10.1%) showed intratumoral heterogeneity; 5 (7.2%) at KRAS codons 12, 13 and 2 (2.9%) at BRAF codon 600. In patients displaying heterogeneity, the relevant KRAS or BRAF mutation was also identified in ‘DNA cocktail’ samples when including DNA from mutant and wild-type blocks. Heterogeneity is uncommon but not insignificant. Testing DNA from a single block will wrongly assign wild-type status to 10% patients. Testing more than one block, or preferably preparation of a ‘DNA cocktail’ from two or more tumor blocks, improves mutation detection at minimal extra cost.
Automatic Security Assessment for Next Generation Wireless Mobile Networks
Authors: Palmieri Francesco , Fiore Ugo , Castiglione Aniello
Published: January 2015

Wireless networks are more and more popular in our life, but their increasing pervasiveness and widespread coverage raises serious security concerns. Mobile client devices potentially migrate, usually passing through very light access control policies, between numerous and heterogeneous wireless environments, bringing with them software vulnerabilities as well as possibly malicious code. To cope with these new security threats the paper proposes a new active third party authentication, authorization and security assessment strategy in which, once a device enters a new Wi-Fi environment, it is subjected to analysis by the infrastructure, and if it is found to be dangerously insecure, it is immediately taken out from the network and denied further access until its vulnerabilities have been fixed. The security assessment module, that is the fundamental component of the aforementioned strategy, takes advantage from a reliable knowledge base containing semantically-rich information about the mobile node under examination, dynamically provided by network mapping and configuration assessment facilities. It implements a fully automatic security analysis framework, based on AHP, which has been conceived to be flexible and customizable, to provide automated support for real-time execution of complex security/risk evaluation tasks which depends on the results obtained from different kind of analysis tools and methodologies. Encouraging results have been achieved utilizing a proof-of-concept model based on current technology and standard open-source networking tools.
A Handover Security Mechanism Employing the Diffie-Hellman Key Exchange Approach for the IEEE802.16e Wireless Networks
Authors: Ciou Yi-Fu , Leu Fang-Yie , Huang Yi-Li , Yim Kangbin
Published: January 2015

In this paper, we propose a handover authentication mechanism, called the handover key management and authentication scheme (HaKMA for short), which as a three-layer authentication architecture is a new version of our previous work, the Diffie-Hellman-PKDS-based authentication method (DiHam for short) improving its key generation flow and adding a handover authentication scheme to respectively speed up the handover process and increase the security level for mobile stations (MSs). AAA server supported authentication is also enhanced by invoking an improved extensible authentication protocol (EAP). According to the analyses of this study the HaKMA can effectively and efficiently provide user authentication and balance data security and system performance during handover.
Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy
Authors: Pasello Michela , Manara Maria Cristina , Michelacci Francesca , Fanelli Marilù , Hattinger Claudia Maria , Nicoletti Giordano , Landuzzi Lorena , Lollini Pier Luigi , Caccuri Annamaria , Picci Piero , Scotlandi Katia , Serra Massimo
Published: January 2015

Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevantin vitroactivity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. Thein vitroactivity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.
Improving Accuracy for Matrix Multiplications on GPUs
Authors: Badin Matthew , Bic Lubomir , Dillencourt Michael , Nicolau Alexandru
Published: January 2015

Reproducibility of an experiment is a commonly used metric to determine its validity. Within scientific computing, this can become difficult due to the accumulation of floating point rounding errors in the numerical computation, greatly reducing the accuracy of the computation. Matrix multiplication is particularly susceptible to these rounding errors which is why there exist so many solutions, ranging from simulating extra precision to compensated summation algorithms. These solutions however all suffer from the same problem, abysmal performance when compared against the performance of the original algorithm. Graphics cards are particularly susceptible due to a lack of double precision on all but the most recent generation graphics cards, therefore increasing the accuracy of the precision that is offered becomes paramount. By using our method of selectively applying compensated summation algorithms, we are able to return a whole digit of accuracy on current generation graphics cards and potentially two digits of accuracy on the newly released “fermi” architecture. This is all possible with only a 2% drop in performance.
A Web-Based Application of TELOSB Sensor Network
Authors: Sheltami Tarek R. , Shakshuki Elhadi M. , Mouftah Hussein T.
Published: January 2015

Sensor network can be used in a numerous number of applications. However, implementing wireless sensor networks present new challenges compared with theoretical networks. In addition, implementing a sensor network might provide results different from that derived theoretically. Some routing protocols when implemented might fail to perform. In this paper, we implement three routing protocols, namely: Dynamic MANET on-demand, Collection Tree and Dissemination protocols. To compare the performance of these protocols, they are implemented using a Telosb sensor network. Several performance metrics are carried out to demonstrate the pros and cons of these protocols. A telemedicine application is tested in top of the implemented Telosb sensor network at King Fahd University of Petroleum and Minerals Clinic in Saudi Arabia, utilizing Alive ECG sensors.
Biophysical Profiling of Tumor Cell Lines
Authors: Coffman Frederick , Hamid Rachid , Cohen Marion C. , Garippa Ralph , Cohen Stanley
Published: January 2015

Despite significant differences in genetic profiles, cancer cells share common phenotypic properties, including membrane-associated changes that facilitate invasion and metastasis. The Corning Epic® optical biosensor was used to monitor dynamic mass rearrangements within and proximal to the cell membrane in tumor cell lines derived from cancers of the colon, bone, cervix, lung and breast. Data was collected in real time and required no exogenously added signaling moiety (signal-free technology). Cell lines displayed unique profiles over the time-courses: the time-courses all displayed initial signal increases to maximal values, but the rate of increase to those maxima and the value of those maxima were distinct for each cell line. The rate of decline following the maxima also differed among cell lines. There were correlations between the signal maxima and the observed metastatic behavior of the cells in xenograft experiments; for most cell types the cells that were more highly metastatic in mice had lower time-course maxima values, however the reverse was seen in breast cancer cells. The unique profiles of these cell lines and the correlation of at least one profile characteristic with metastatic behavior demonstrate the potential utility of biophysical tumor cell profiling in the study of cancer biology.
Expression of a Secretory Protein C1qTNF6, a C1qTNF Family Member, in Hepatocellular Carcinoma
Authors: Takeuchi Tamotsu , Adachi Yoshihiro , Nagayama Tomoko
Published: January 2015

Background: Recent studies have revealed that the adiponectin-associated protein belonging to the C1qTNF family mediates various biological processes. However, the pathobiological property of C1qTNF6 in carcinogenesis remains unclear. Here, we investigated the expression status of C1qTNF6 in human hepatocellular carcinomas and subsequently attempted to determine the role of C1qTNF6 in tumor neovascularization. Methods: Immunohistochemical staining was performed to evaluate the expression of C1qTNF6 in hepatocellular carcinoma tissue specimens. Various eukaryotic recombinant C1qTNF6 proteins were prepared to ask whether C1qTNF6 could activate Akt pathway in human liver sinusoidal microvascular endothelial cells. Xenograft assay was carried out to know the effect of C1qTNF6 on tumor neovascularization. Results: C1qTNF6 was not immunohistochemically detected in any non-cancerous liver tissues but was detected in 21 of 30 hepatocellular carcinoma tissue specimens. C1qTNF6 was not uniformly distributed but rather focally localized in hepatocellular carcinoma cells. Interestingly, it was also localized on the tumor endothelial cells, which were in close proximity of C1qTNF6-expressing hepatocellular carcinoma cells. Eukaryotic recombinant C1qTNF6 increased the level of active phosphorylated Akt molecules in cultured vascular endothelial cells via its C-terminal C1q domain. In the xenograft assay, enforced expression of C1qTNF6 markedly reduced the central hypovascular necrosis areas of the transplanted HepG2 hepatocellular carcinoma cells. Conclusion: These results indicate that C1qTNF6 is overexpressed and possibly contributes to tumor angiogenesis by activating the Akt pathway in many hepatocellular carcinomas.
QoS Routing in Ad-Hoc Networks Using GA and Multi-Objective Optimization
Authors: Barolli Admir , Spaho Evjola , Barolli Leonard , Xhafa Fatos , Takizawa Makoto
Published: January 2015

Much work has been done on routing in Ad-hoc networks, but the proposed routing solutions only deal with the best effort data traffic. Connections with Quality of Service (QoS) requirements, such as voice channels with delay and bandwidth constraints, are not supported. The QoS routing has been receiving increasingly intensive attention, but searching for the shortest path with many metrics is an NP-complete problem. For this reason, approximated solutions and heuristic algorithms should be developed for multi-path constraints QoS routing. Also, the routing methods should be adaptive, flexible, and intelligent. In this paper, we use Genetic Algorithms (GAs) and multi-objective optimization for QoS routing in Ad-hoc Networks. In order to reduce the search space of GA, we implemented a search space reduction algorithm, which reduces the search space for GAMAN (GA-based routing algorithm for Mobile Ad-hoc Networks) to find a new route. We evaluate the performance of GAMAN by computer simulations and show that GAMAN has better behaviour than GLBR (Genetic Load Balancing Routing).
A Cluster-Based Web Service Discovery in MANET Environments
Authors: Kim Yeon-Seok , Shim Yoo-Seok , Lee Kyong-Ho
Published: January 2015

As standard technologies to implement a service-oriented architecture, Web services support interoperability between heterogeneous platforms. In the ubiquitous era, for Web services to become a universal software development paradigm, they must be able to support a MANET environment with a variety of mobile devices. In this paper, we propose an efficient method that discovers services in MANET environments, where mobile devices are free to move independently. The proposed method constructs stable clusters based on the mobility of devices. It also selects an appropriate service discovery scheme for a cluster depending on its characteristics. Experimental results show that the proposed method outperforms previous methods, and discovers services based on the features of a cluster.
A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast
Authors: Edgerton Mary E. , Chuang Yao-Li , Macklin Paul , Yang Wei , Bearer Elaine L. , Cristini Vittorio
Published: January 2015

We introduce a novel “mathematical pathology” approach, founded on a biophysical model, to identify robust patient-specific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limitedin situtumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected byin situtumors at the time of diagnosis will be closely approximated by a model-derived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinomain situfor mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R2= 0.74—0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R2= 0.08—0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery.
Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
Authors: Timme Sylvia , Schmitt Eberhard , Stein Stefan , Schwarz-Finsterle Jutta , Wagner Jenny , Walch Axel , Werner Martin , Hausmann Michael , Wiech Thorsten
Published: January 2015

Cell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8) in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH) with whole chromosome painting (WCP) probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma.