bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Bluetooth to Implement a Pervasive Indoor Positioning System with Minimal Requirements at the Application Level
Authors: Muñoz-Organero Mario , Muñoz-Merino Pedro J. , Delgado Kloos Carlos
Published: January 2015

Different systems have been proposed to estimate the position of a mobile device using Bluetooth based on metrics such as the Radio Signal Strength Indicator (RSSI), the received Bit Error Rate (BER) or the Cellular Signal Quality (CSQ). These systems try to improve the estimation accuracy of the basic and straightforward triangulation method among discovered BT reference base stations at the cost of requiring that the positioning application has access to low level hardware related data (provided by the Host Controller Interface) and obtaining information which is in many cases hardware, and therefore device, dependent. In this paper we design, simulate, implement and validate a Bluetooth positioning system that only requires the ability to handle SDP service records at the application level, achieving mean errors around 1 to 3 meters, improving the basic triangulation method among discovered BT reference base stations.
Combined Scheduling and Mapping for Scalable Computing with Parallel Tasks
Authors: Dümmler Jörg , Rauber Thomas , Rünger Gudula
Published: January 2015

Recent and future parallel clusters and supercomputers use symmetric multiprocessors (SMPs) and multi-core processors as basic nodes, providing a huge amount of parallel resources. These systems often have hierarchically structured interconnection networks combining computing resources at different levels, starting with the interconnect within multi-core processors up to the interconnection network combining nodes of the cluster or supercomputer. The challenge for the programmer is that these computing resources should be utilized efficiently by exploiting the available degree of parallelism of the application program and by structuring the application in a way which is sensitive to the heterogeneous interconnect. In this article, we pursue a parallel programming method using parallel tasks to structure parallel implementations. A parallel task can be executed by multiple processors or cores and, for each activation of a parallel task, the actual number of executing cores can be adapted to the specific execution situation. In particular, we propose a new combined scheduling and mapping technique for parallel tasks with dependencies that takes the hierarchical structure of modern multi-core clusters into account. An experimental evaluation shows that the presented programming approach can lead to a significantly higher performance compared to standard data parallel implementations.
A Novel Gene RNF138 Expressed in Human Gliomas and Its Function in the Glioma Cell Line U251
Authors: Zhou You-xin , Chen San-song , Wu Ting-feng , Ding Da-dong , Chen Xiong-hui , Chen Jin-ming , Su Zuo-peng , Li Bin , Chen Gui-lin , Xie Xue-shun , Dai Yan-fang , Wei Yong-xin , Du Zi-wei
Published: January 2015

Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes and the inactivation of tumor suppressor genes. Whether the RING finger protein, RNF138, a newly discovered protein, plays a role in glioma oncogenesis is unknown. The present study investigates the expression levels of RNF138 mRNA in glioma samples and noncancerous brain samples and its function in the human glioma cell line U251.

Methods: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of 35 pathological confirmed glioma samples (Grade I – 4 cases, Grade II – 13 cases, Grade III – 11 cases, and Grade IV – 7 cases) and five noncancerous brain tissue samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi) with the lentivirus vector system, the expression of RNF138 was inhibited in the human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138-knockdown on cell proliferation were assessed by Cellomics, and cell cycle and cell apoptosis were assessed by FACS.

Results: The RNF138 mRNA is expressed in the five glioma cell lines, and its expression level is significantly higher in glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138 expression, U251 cell proliferation was inhibited and cell apoptosis increased. At the same time, S stage cells lessened and G2 stage cells increased.

Conclusion: The RNF138 gene is highly expressed in glioma tissue and glioma cell lines. It plays an important role in glioma cell proliferation, apoptosis, and cell cycle.
Playa: High-Performance Programmable Linear Algebra
Authors: Howle Victoria E. , Kirby Robert C. , Long Kevin , Brennan Brian , Kennedy Kimberly
Published: January 2015

This paper introduces Playa, a high-level user interface layer for composing algorithms for complex multiphysics problems out of objects from other Trilinos packages. Among other features, Playa provides very high-performance overloaded operators implemented through an expression template mechanism. In this paper, we give an overview of the central Playa objects from a user's perspective, show application to a sequence of increasingly complex solver algorithms, provide timing results for Playa's overloaded operators and other functions, and briefly survey some of the implementation issues involved.
A Role of Three-Dimensional (3D)-Reconstruction in the Classification of Lung Adenocarcinoma
Authors: Onozato Maristela L. , Klepeis Veronica E. , Yagi Yukako , Mino-Kenudson Mari
Published: January 2015

Background: Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas and different fields of view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, the most frequent histology type of lung cancer characterized by its morphological heterogeneity.

Objective: In this work, we tested whether an automated tissue sectioning machine and slide scanning system could generate precise 3D-reconstruction of microanatomy of the lung and help us better understand and define histologic subtypes of lung adenocarcinoma.

Methods: Four formalin-fixed human lung adenocarcinoma resections were studied. Paraffin embedded tissues were sectioned with Kurabo-Automated tissue sectioning machine and serial sections were automatically stained and scanned with a Whole Slide Imaging system. The resulting stacks of images were 3D reconstructed by Pannoramic Viewer software.

Results: Two of the four specimens contained islands of tumor cells detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications. 3D-reconstruction revealed the details of spatial distribution and structural interaction of the tumor that could hardly be observed by 2D light microscopy studies. The islands of tumor cells extended into a deeper aspect of the tissue, and were interconnected with each other and with the main tumor with a solid pattern that was surrounded by the islands. The finding raises the question whether the islands of tumor cells should be classified into a solid pattern in the current classification.

Conclusion: The combination of new technologies enabled us to build an effective 3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us refine the classification of lung adenocarcinoma by adding detailed spatial/structural information to 2D light microscopy evaluation.
Tpetra, and the Use of Generic Programming in Scientific Computing
Authors: Baker C.G. , Heroux M.A.
Published: January 2015

We present Tpetra, a Trilinos package for parallel linear algebra primitives implementing the Petra object model. We describe Tpetra's design, based on generic programming via C++ templated types and template metaprogramming. We discuss some benefits of this approach in the context of scientific computing, with illustrations consisting of code and notable empirical results.
The Zoltan and Isorropia Parallel Toolkits for Combinatorial Scientific Computing: Partitioning, Ordering and Coloring
Authors: Boman Erik G. , Çatalyürek Ümit V. , Chevalier Cédric , Devine Karen D.
Published: January 2015

Partitioning and load balancing are important problems in scientific computing that can be modeled as combinatorial problems using graphs or hypergraphs. The Zoltan toolkit was developed primarily for partitioning and load balancing to support dynamic parallel applications, but has expanded to support other problems in combinatorial scientific computing, including matrix ordering and graph coloring. Zoltan is based on abstract user interfaces and uses callback functions. To simplify the use and integration of Zoltan with other matrix-based frameworks, such as the ones in Trilinos, we developed Isorropia as a Trilinos package, which supports most of Zoltan's features via a matrix-based interface. In addition to providing an easy-to-use matrix-based interface to Zoltan, Isorropia also serves as a platform for additional matrix algorithms. In this paper, we give an overview of the Zoltan and Isorropia toolkits, their design, capabilities and use. We also show how Zoltan and Isorropia enable large-scale, parallel scientific simulations, and describe current and future development in the next-generation package Zoltan2.
Integrated Context-Aware Driver Assistance System Architecture
Authors: Shakshuki Elhadi M. , Alghamdi Wael , Sheltami Tarek
Published: January 2015

Recently, significant improvements have been made in the area of vehicular communication systems. Furthermore, vehicle-to-vehicle communication is considered a key concept for keeping roads safe. An efficient implementation of these systems is necessary to ensure the safety of driving situations and to reduce the collision rates. This paper proposes a Context-Aware Driver Assistance System that links drivers with the physical environment surrounding them using multiple types of sensors and traffic systems as well as considering the senior driver's difficulties and the system processing time. This is achieved by developing a warning system that assists drivers to avoid collisions and improve their response times. The proposed system architecture consists of a set of components to process the user's request such as parking assistance, and to provide responses and advices when needed. These components include communication, knowledge exchange, knowledge update, and context-history. Also, it includes other processes such as context-history manipulation, hazard detection, and hazard detection control. The main goal of the proposed system is to reduce the number of car accidents and improve driver's decisions. The NXT Robotic environment is used to demonstrate the feasibility of the proposed system.
Study on Interaction of Cationic Porphyrazine with Synthetic Polynucleotides
Authors: Dezhampanah Hamid , Fyzolahjani Soghra
Published: January 2015

Interactions of cationic tetrakis (N, N′, N″, N‴- tetramethyltetra-3, 4-pyridinoporphyrazinatozinc (II) (Zn (tmtppa)) with synthetic polynucleotides, poly (G-C) and poly (A-T), and calf thymus DNA have been characterized in 7.5 mM phosphate buffer of pH 7.2 by UV-Vis absorption and fluorescence spectroscopy. The appearance of hypochromicity more than 30% in UV-Vis spectra of porphyrazine due to interaction of both poly (G-C) and poly (A-T) indicates interaction similar to that of porphyrazine with DNA.

The binding constants were determined from the changes in the Q-band maximum of the porphyrazine spectra at various poly (G-C) and DNA concentrations. The values of K were 2.5 × 106M−1, 2.5 × 106M−1and 2.5 × 105M−1for poly (G-C), poly (A-T) and DNA, respectively, at 25°C. The thermodynamic parameters (ΔG°, ΔH°, ΔS°) were calculated using the van't Hoff equation at various temperatures. The enthalpy and entropy changes were determined to be 41.14 kJ mol−1and 260.50 J mol−1·K−1for poly (G-C) and 53.59 kJ mol−1and 285.46 J mol−1·K−1for DNA at 25°C. The positive and large values of the entropy and enthalpy suggest that both hydrophobic and electrostatic interactions may play an important role in the stabilization of the complex formation. The binding of polynucleotides to porphyrazine quenches fluorescence emission of ethidium bromide (EB), and the quenching process obeys linear Stern-Volmer relationship. The results reviled groove-binding mode of porphyrazine for both AT- and GC-rich polynucleotides of DNA.
Spectroscopic Studies on the Interaction of a Water-Soluble Cationic Porphyrin with Bovine Serum Albumin
Authors: Dezhampanah Hamid , Bordbar Abdol-Khalegh , Khodadusdt Yadolahe
Published: January 2015

The interaction of a water-soluble cationic porphyrin, Cobalt(III) 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin [Co(III)TMPyP], with bovine serum albumin (BSA) has been studied in 1 mM phosphate buffer pH 7.0 containing 5 mM NaCl by UV-vis absorption, resonance light scattering (RLS) and fluorescence spectroscopies at 25°C. The results of RLS studies represent no aggregate formation of porphyrin in the surface of BSA and low tendency of this porphyrin for aggregate formation.

The binding of porphyrin complex to BSA quenches fluorescence emission of BSA via a dynamic mechanism and the quenching process obeys a linear Stern-Volmer relationship. The values of Stern-Volmer constants, KSV, was determined nearly 105M−1, that depend on BSA concentration. The average aggregation number of BSA calculated from the analysis of fluorescence quenching data indicates that absence of any porphyrin induced aggregation of BSA due to its interaction with porphyrin complex. The binding of Co(III) TMPyP had no obvious effect on the molecular conformation of the protein. Electrostatic force played an important role in the binding due to the opposite charges on porphyrin and the protein.
Template Metaprogramming Techniques for Concept-Based Specialization
Authors: Bachelet Bruno , Mahul Antoine , Yon Loïc
Published: January 2015

In generic programming, software components are parameterized on types. When available, a static specialization mechanism allows selecting, for a given set of parameters, a more suitable version of a generic component than its primary version. The normal C++ template specialization mechanism is based on the type pattern of the parameters, which is not always the best way to guide the specialization process: type patterns are missing some information on types that could be relevant to define specializations. The notion of a concept, which represents a set of requirements (including syntactic and semantic aspects) for a type, is known to be an interesting approach to control template specialization. For many reasons, concepts were dropped from C++11 standard, this article therefore describes template metaprogramming techniques for declaring concepts, modeling relationships (meaning that a type fulfills the requirements of a concept), and refinement relationships (meaning that a concept refines the requirements of another concept). From a taxonomy of concepts and template specializations based on concepts, an automatic mechanism selects the most appropriate version of a generic component for a given instantiation. Our purely library-based solution is also open for retroactive extension: new concepts, relationships, and template specializations can be defined at any time; such additions will then be picked up by the specialization mechanism.
Health Participatory Sensing Networks
Authors: Clarke Andrew , Steele Robert
Published: January 2015

The use of participatory sensing in relation to the capture of health-related data is rapidly becoming a possibility due to the widespread consumer adoption of emerging mobile computing technologies and sensing platforms. This has the potential to revolutionize data collection for population health, aspects of epidemiology, and health-related e-Science applications and as we will describe, provide new public health intervention capabilities, with the classifications and capabilities of such participatory sensing platforms only just beginning to be explored. Such a development will have important benefits for access to near real-time, large-scale, up to population-scale data collection. However, there are also numerous issues to be addressed first: provision of stringent anonymity and privacy within these methodologies, user interface issues, and the related issue of how to incentivize participants and address barriers/concerns over participation. To provide a step towards describing these aspects, in this paper we present a first classification of health participatory sensing models, a novel contribution to the literature, and provide a conceptual reference architecture for health participatory sensing networks (HPSNs) and user interaction example case study.
Observer Performance in the Use of Digital and Optical Microscopy for the Interpretation of Tissue-Based Biomarkers
Authors: Gavrielides Marios A. , Conway Catherine , O’Flaherty Neil , Gallas Brandon D. , Hewitt Stephen M.
Published: January 2015

Background.We conducted a validation study of digital pathology for the quantitative assessment of tissue-based biomarkers with immunohistochemistry.Objective.To examine observer agreement as a function of viewing modality (digital versus optical microscopy), whole slide versus tissue microarray (TMA) review, biomarker type (HER2 incorporating membranous staining and Ki-67 with nuclear staining), and data type (continuous and categorical).Methods.Eight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97 cores), using digital and optical microscopy.Results.Results showed relatively high overall interobserver and intermodality agreement, with different patterns specific to biomarker type. For HER2, there was better interobserver agreement for optical compared to digital microscopy for whole slides as well as better interobserver and intermodality agreement for TMAs. For Ki-67, those patterns were not observed.Conclusions.The differences in agreement patterns when examining different biomarkers and different scoring methods and reviewing whole slides compared to TMA stress the need for validation studies focused on specific pathology tasks to eliminate sources of variability that might dilute findings. The statistical uncertainty observed in our analyses calls for adequate sampling for each individual task rather than pooling cases.
RLAM: A Dynamic and Efficient Reinforcement Learning-Based Adaptive Mapping Scheme in Mobile WiMAX Networks
Authors: Louta M. , Sarigiannidis P. , Misra S. , Nicopolitidis P. , Papadimitriou G.
Published: January 2015

WiMAX (Worldwide Interoperability for Microwave Access) constitutes a candidate networking technology towards the 4G vision realization. By adopting the Orthogonal Frequency Division Multiple Access (OFDMA) technique, the latest IEEE 802.16x amendments manage to provide QoS-aware access services with full mobility support. A number of interesting scheduling and mapping schemes have been proposed in research literature. However, they neglect a considerable asset of the OFDMA-based wireless systems: the dynamic adjustment of the downlink-to-uplink width ratio. In order to fully exploit the supported mobile WiMAX features, we design, develop, and evaluate a rigorous adaptive model, which inherits its main aspects from the reinforcement learning field. The model proposed endeavours to efficiently determine the downlink-to-uplinkwidth ratio, on a frame-by-frame basis, taking into account both the downlink and uplink traffic in the Base Station (BS). Extensive evaluation results indicate that the model proposed succeeds in providing quite accurate estimations, keeping the average error rate below 15% with respect to the optimal sub-frame configurations. Additionally, it presents improved performance compared to other learning methods (e.g., learning automata) and notable improvements compared to static schemes that maintain a fixed predefined ratio in terms of service ratio and resource utilization.
Enabling Highly-Scalable Remote Memory Access Programming with MPI-3 One Sided
Authors: Gerstenberger Robert , Besta Maciej , Hoefler Torsten
Published: January 2015

Modern interconnects offer remote direct memory access (RDMA) features. Yet, most applications rely on explicit message passing for communications albeit their unwanted overheads. The MPI-3.0 standard defines a programming interface for exploiting RDMA networks directly, however, it's scalability and practicability has to be demonstrated in practice. In this work, we develop scalable bufferless protocols that implement the MPI-3.0 specification. Our protocols support scaling to millions of cores with negligible memory consumption while providing highest performance and minimal overheads. To arm programmers, we provide a spectrum of performance models for all critical functions and demonstrate the usability of our library and models with several application studies with up to half a million processes. We show that our design is comparable to, or better than UPC and Fortran Coarrays in terms of latency, bandwidth and message rate. We also demonstrate application performance improvements with comparable programming complexity.
Reducing Energy Waste through Eco-Aware Everyday Things
Authors: López-de-Armentia Juan , Casado-Mansilla Diego , López-Pérez Sergio , López-de-Ipiña Diego
Published: January 2015

Society wastes much more energy than it should. This produces tons of unnecessary CO2 emissions. This is partly due to the inadequate use of electrical devices given the intangible and invisible nature of energy. This misuse of devices and energy unawareness is particularly relevant in public spaces (offices, schools, hospitals and so on), where people use electrical appliances, but they do not directly pay the invoice to energy providers. Embedding intelligence within public, shared appliances, transforming them into Eco-aware things, is valuable to reduce a proportion of the unnecessarily consumed energy. To this end, we present a twofold approach for better energy efficiency in public spaces: (1) informing persuasively to concerned users about the misuse of electronic appliances; (2) Customizing the operating mode of this everyday electrical appliances as a function of their real usage pattern. To back this approach, a capsule-based coffee machine placed in a research laboratory has been augmented. This device is able to continuously collect its usage pattern to offer feedback to coffee consumers about the energy wasting and also, to intelligently adapt its operation to reduce wasted energy. To this aim, several machine learning approaches are compared and evaluated to forecast the next-day device usage.
Central Nervous System Tuberculosis: An Imaging-Focused Review of a Reemerging Disease
Authors: Sanei Taheri Morteza , Karimi Mohammad Ali , Haghighatkhah Hamidreza , Pourghorban Ramin , Samadian Mohammad , Delavar Kasmaei Hosein
Published: January 2015

Central nervous system (CNS) tuberculosis is a potentially life threatening condition which is curable if the correct diagnosis is made in the early stages. Its clinical and radiologic manifestations may mimic other infectious and noninfectious neurological conditions. Hence, familiarity with the imaging presentations of various forms of CNS tuberculosis is essential in timely diagnosis, and thereby reducing the morbidity and mortality of this disease. In this review, we describe the imaging characteristics of the different forms of CNS tuberculosis, including meningitis, tuberculoma, miliary tuberculosis, abscess, cerebritis, and encephalopathy.
A Challenging Case of a Large Gastroduodenal Artery Pseudoaneurysm after Surgery of a Peptic Ulcer
Authors: Santos-Rancaño Rocio , Antona Esteban Martín , Montero José Vicente Méndez
Published: January 2015

We report a 48-year-old man in whom a chronic postbulbar duodenal ulcer destroyed much of the back wall of the duodenum and gastroduodenal artery causing pseudoaneurysm. The lesion was found and evaluated by contrast-enhanced computed tomography (that revealed a large pseudoaneurysm of 83 mm×75 mm in diameter) and by angiography and then treated with transcatheter embolization leading to a complete resolution of the lesion. The case is rare and important for several reasons. First, we demonstrate that pseudoaneurysm of the gastroduodenal artery caused by a duodenal ulcer can occur and present a diagnostic challenge (as far as we know, only three cases have been reported previously in the literature). Second, this case report focuses on the importance of ligation of the gastroduodenal artery when bleeding of peptic ulcers occurs. Additionally, we present an overview of the relevant literature.
PhosphoHunter: An Efficient Software Tool for Phosphopeptide Identification
Authors: Tiengo Alessandra , Pasotti Lorenzo , Barbarini Nicola , Magni Paolo
Published: January 2015

Phosphorylation is a protein posttranslational modification. It is responsible of the activation/inactivation of disease-related pathways, thanks to its role of “molecular switch.” The study of phosphorylated proteins becomes a key point for the proteomic analyses focused on the identification of diagnostic/therapeutic targets. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the most widely used analytical approach. Although unmodified peptides are automatically identified by consolidated algorithms, phosphopeptides still require automated tools to avoid time-consuming manual interpretation. To improve phosphopeptide identification efficiency, a novel procedure was developed and implemented in a Perl/C tool called PhosphoHunter, here proposed and evaluated. It includes a preliminary heuristic step for filtering out the MS/MS spectra produced by nonphosphorylated peptides before sequence identification. A method to assess the statistical significance of identified phosphopeptides was also formulated. PhosphoHunter performance was tested on a dataset of 1500 MS/MS spectra and it was compared with two other tools: Mascot and Inspect. Comparisons demonstrated that a strong point of PhosphoHunter is sensitivity, suggesting that it is able to identify real phosphopeptides with superior performance. Performance indexes depend on a single parameter (intensity threshold) that users can tune according to the study aim. All the three tools localized >90% of phosphosites.
Transition Metal Ion Implantation into Diamond‐Like Carbon Coatings: Development of a Base Material for Gas Sensing Applications
Authors: Markwitz Andreas , Leveneur Jérôme , Gupta Prasanth , Suschke Konrad , Futter John , Rondeau Morgane
Published: January 2015

Micrometre thick diamond‐like carbon (DLC) coatings produced by direct ion deposition were implanted with 30 keV Ar+ and transition metal ions in the lower percentage (<10 at.%) range. Theoretical calculations showed that the ions are implanted just beneath the surface, which was confirmed with RBS measurements. Atomic force microscope scans revealed that the surface roughness increases when implanted with Ar+ and Cu+ ions, whereas a smoothing of the surface from 5.2 to 2.7 nm and a grain size reduction from 175 to 93 nm are measured for Ag+ implanted coatings with a fluence of 1.24 × 1016 at. cm−2. Calculated hydrogen and carbon depth profiles showed surprisingly significant changes in concentrations in the near‐surface region of the DLC coatings, particularly when implanted with Ag+ ions. Hydrogen accumulates up to 32 at.% and the minimum of the carbon distribution is shifted towards the surface which may be the cause of the surface smoothing effect. The ion implantations caused an increase in electrical conductivity of the DLC coatings, which is important for the development of solid‐state gas sensors based on DLC coatings.
Atherogenic Dyslipidemia and Cardiovascular Risk Factors in Obese Children
Authors: D’Adamo Ebe , Guardamagna Ornella , Chiarelli Francesco , Bartuli Andrea , Liccardo Daniela , Ferrari Federica , Nobili Valerio
Published: January 2015

Childhood obesity when associated with serum lipoprotein changes triggers atherosclerosis. Evidences suggest that the atherosclerotic process begins in childhood and that the extent of early atherosclerosis of the aorta and coronary arteries can be associated with lipoprotein levels and obesity. Furthermore, many studies in childhood demonstrate an important relationship between parameters of insulin sensitivity, body fat distribution, and the development of lipid abnormalities. This review focuses on the most recent findings on the relationship between obesity, dyslipidemia, and cardiovascular risk in children.
XCP-Winf and RCP-Winf: Improving Explicit Wireless Congestion Control
Authors: Barreto Luís
Published: January 2015

Congestion control in wireless networks is strongly dependent on the dynamics and instability of wireless links. Therefore, it is very difficult to accurately evaluate the characteristics of the wireless links. It is known that TCP experiences serious performance degradation problems in wireless networks. Moreover, congestion control mechanisms that rely on network interaction and network parameters, such as XCP and RCP, do not evaluate accurately the capacity and available link bandwidth in wireless networks. In this paper we propose new explicit flow control protocols for wireless mesh networks, based on XCP and RCP. We name these protocols XCP-Winf and RCP-Winf. They rely on the MAC layer information gathered by a new method to accurately estimate the available bandwidth and the path capacity over a wireless network path. The estimation is performed in real time and without the need to intrusively inject packets in the network. These new congestion control mechanisms are evaluated in different scenarios in wireless mesh and ad hoc networks and compared against several new approaches for wireless congestion control. It is shown that both XCP-Winf and RCP-Winf outperform the evaluated approaches, showing its stable behavior and better channel utilization.
Interferon Regulatory Factor-1 Signaling Regulates the Switch between Autophagy and Apoptosis to Determine Breast Cancer Cell Fate
Authors: Schwartz-Roberts Jessica L. , Cook Katherine L. , Chen Chun , Shajahan-Haq Ayesha N. , Axelrod Margaret , Wärri Anni , Riggins Rebecca B. , Jin Lu , Haddad Bassem R. , Kallakury Bhaskar V. , Baumann William T. , Clarke Robert
Published: January 2015

Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell fate in several cell types. Here, we report an inverse correlation in expression of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells that directly affects their cell fate. In mice harboring mutant Atg7, nuclear IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic investigations identified ATG7 and the cell death modulator beclin-1 (BECN1) as negative regulators of IRF1. Silencing ATG7 or BECN1 caused estrogen receptor-α to exit the nucleus at the time when IRF1 nuclear localization occurred. Conversely, silencing IRF1 promoted autophagy by increasing BECN1 and blunting IGF1 receptor and mTOR survival signaling. Loss of IRF1 promoted resistance to antiestrogens, whereas combined silencing of ATG7 and IRF1 restored sensitivity to these agents. Using a mathematical model to prompt signaling hypotheses, we developed evidence that ATG7 silencing could resensitize IRF1-attenuated cells to apoptosis through mechanisms that involve other estrogen-regulated genes. Overall, our work shows how inhibiting the autophagy proteins ATG7 and BECN1 can regulate IRF1-dependent and -independent signaling pathways in ways that engender a new therapeutic strategy to attack breast cancer. Cancer Res; 75(6); 1046–55. ©2015 AACR.
Redundancy: A Critical Obstacle to Improving Cancer Therapy
Authors: Lavi Orit
Published: January 2015

A system characterized by redundancy has various elements that are able to act in the same biologic or dynamic manner, where the inhibition of one of those elements has no significant effect on the global biologic outcome or on the system's dynamic behavior. Methods that aim to predict the effectiveness of cancer therapies must include evolutionary and dynamic features that would change the static view that is widely accepted. Here, we explore several important issues about mechanisms of redundancy, heterogeneity, biologic importance, and drug resistance and describe methodologic challenges that, if overcome, would significantly contribute to cancer research. Cancer Res; 75(5); 808–12. ©2015 AACR.
Geospatial Patterns in Human Papillomavirus Vaccination Uptake: Evidence from Uninsured and Publicly Insured Children in North Carolina
Authors: Trogdon Justin G. , Ahn Thomas
Published: January 2015

Background: Human papillomavirus (HPV) vaccination coverage is far below the national objective set by Healthy People 2020. This paper explores spatial patterns in HPV vaccination uptake.

Methods: Secondary data for publicly funded HPV vaccinations among age-eligible children from 2008 through 2013 from the North Carolina Immunization Registry (NCIR) were used in 2014 in an ecological analysis at the ZIP code tabulation area (ZCTA) level. We tested for spatial autocorrelation in unadjusted HPV vaccination rates using choropleth maps and Moran's I. We estimated nonspatial and spatial negative binomial models with spatially correlated random effects adjusted for demographic, economic, and healthcare variables drawn from the 2010 U.S. Census Bureau, 2008–2012 American Community Survey, 2010 ZIP Business Patterns, and the 2012–2013 Area Resource File.

Results: The NCIR revealed areas of especially low rates in publicly funded HPV vaccinations among uninsured and means-tested, publicly insured children. For boys, but not girls, ZCTAs tended to have HPV vaccination rates that were similar to their neighbors. This result was partially explained by included ZCTA characteristics, but not wholly.

Conclusions: To the extent that the geospatial clustering of vaccination rates is due to causal influences from one ZCTA to another (e.g., through information networks), targeting interventions to increase HPV vaccination in one area could also lead to increases in neighboring areas.

Impact: Spatial targeting of HPV vaccination, especially in clusters of low vaccination areas, could be an effective strategy to reduce the spread of HPV and related cancers. Cancer Epidemiol Biomarkers Prev; 24(3); 595–602. ©2015 AACR.
Long-term Persistence of Oral Human Papillomavirus Type 16: The HPV Infection in Men (HIM) Study
Authors: Pierce Campbell Christine M. , Kreimer Aimée R. , Lin Hui-Yi , Fulp William , O'Keefe Michael T. , Ingles Donna J. , Abrahamsen Martha , Villa Luisa L. , Lazcano-Ponce Eduardo , Giuliano Anna R.
Published: January 2015

Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan–Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25–42] and were followed for a median of 44.4 months (IQR, 29.9–49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4–NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. Cancer Prev Res; 8(3); 190–6. ©2015 AACR.
Peptide/MHC Tetramer–Based Sorting of CD8+ T Cells to a Leukemia Antigen Yields Clonotypes Drawn Nonspecifically from an Underlying Restricted Repertoire
Authors: Hunsucker Sally A. , McGary Colleen S. , Vincent Benjamin G. , Enyenihi Atim A. , Waugh Jennifer P. , McKinnon Karen P. , Bixby Lisa M. , Ropp Patricia A. , Coghill James M. , Wood William A. , Gabriel Don A. , Sarantopoulos Stefanie , Shea Thomas C. , Serody Jonathan S. , Alatrash Gheath , Rodriguez-Cruz Tania , Lizée Gregory , Buntzman Adam S. , Frelinger Jeffrey A. , Glish Gary L. , Armistead Paul M.
Published: January 2015

Testing of T cell–based cancer therapeutics often involves measuring cancer antigen–specific T-cell populations with the assumption that they arise from in vivo clonal expansion. This analysis, using peptide/MHC tetramers, is often ambiguous. From a leukemia cell line, we identified a CDK4-derived peptide epitope, UNC-CDK4-1 (ALTPVVVTL), that bound HLA-A*02:01 with high affinity and could induce CD8+ T-cell responses in vitro. We identified UNC-CDK4-1/HLA-A*02:01 tetramer+ populations in 3 of 6 patients with acute myeloid leukemia who had undergone allogeneic stem cell transplantation. Using tetramer-based, single-cell sorting and T-cell receptor β (TCRβ) sequencing, we identified recurrent UNC-CDK4-1 tetramer–associated TCRβ clonotypes in a patient with a UNC-CDK4-1 tetramer+ population, suggesting in vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRβ repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer–associated TCRβ clonotypes represented >17% of the entire TCRβ repertoire—far in excess of the UNC-CDK4-1 tetramer+ frequency—indicating that the recurrent TCRβ clonotypes identified from UNC-CDK-4-1 tetramer+ cells were likely a consequence of the extremely constrained T-cell repertoire in the patient and not in vivo UNC-CDK4-1–driven clonal T-cell expansion. Mapping recurrent TCRβ clonotype sequences onto TCRβ repertoires can help confirm or refute antigen-specific T-cell expansion in vivo. Cancer Immunol Res; 3(3); 228–35. ©2015 AACR.
Functional Tuning of CARs Reveals Signaling Threshold above Which CD8+ CTL Antitumor Potency Is Attenuated due to Cell Fas–FasL-Dependent AICD
Authors: Künkele Annette , Johnson Adam J. , Rolczynski Lisa S. , Chang Cindy A. , Hoglund Virginia , Kelly-Spratt Karen S. , Jensen Michael C.
Published: January 2015

Chimeric antigen receptor (CAR) development is biased toward selecting constructs that elicit the highest magnitude of T-cell functional outputs. Here, we show that components of CAR extracellular spacer and cytoplasmic signaling domain modulate, in a cooperative manner, the magnitude of CD8+CTL activation for tumor-cell cytolysis and cytokine secretion. Unexpectedly, CAR constructs that generate the highest in vitro activity, either by extracellular spacer length tuning or by the addition of cytoplasmic signaling modules, exhibit attenuated antitumor potency in vivo, whereas CARs tuned for moderate signaling outputs mediate tumor eradication. Recursive CAR triggering renders CTLs expressing hyperactive CARs highly susceptible to activation-induced cell death (AICD) as a result of augmented FasL expression. CAR tuning using combinations of extracellular spacers and cytoplasmic signaling modules, which limit AICD of CD8+CTLs, may be a critical parameter for achieving clinical activity against solid tumors. Cancer Immunol Res; 3(4); 368–79. ©2015 AACR.
Metabolic Syndrome Is Associated with Atrial Electrical and Mechanical Dysfunction
Authors: Yilmaz Hale , Özcan Kazım Serhan , Sayar Nurten , Kemaloglu Tugba , Gungor Baris , Erer Betul , Yilmaz Mehmet , Gurkan Ufuk , Cakmak Nazmiye , Oz Dilaver , Calik Ali Nazmi , Bolca Osman
Published: January 2015

Objective: In this study, we aimed to investigate the left atrial (LA) electrical and mechanical functions in patients with metabolic syndrome (MetS). Subjects and Methods: The study population consisted of 87 patients with MetS and 67 controls. Intra-atrial and interatrial electromechanical delays (EDs) were measured with tissue Doppler imaging. P-wave dispersion (Pd) was calculated from the 12-lead electrocardiograms. LA volumes were measured echocardiographically by the biplane area-length method. Results: Intra-atrial and interatrial EDs and Pd were significantly higher in patients with MetS (10.3 ± 6.3, 21.0 ± 11.5 and 41.7 ± 10.8) than in controls (7.4 ± 5.5, 12.3 ± 10.4 and 29.2 ± 7.4; p = 0.003, p < 0.001 and p < 0.001, respectively). The LA preatrial contraction volume and active emptying volumes were higher in this population, but the LA passive emptying fraction was lower. In the multivariate linear regression analysis, the presence of MetS, LA active emptying volume and left ventricular early diastolic (E) wave velocity/late diastolic (A) wave velocity (E/A) ratios were independent correlates of interatrial ED (p = 0.002, p = 0.001 and p = 0.025, respectively). Conclusions: This study showed that intra-atrial and interatrial EDs and Pd were prolonged and LA mechanical functions were impaired in patients with MetS.
Meta-Analysis: Superior Treatment Response in Asian Patients with Hepatitis C Virus Genotype 6 versus Genotype 1 with Pegylated Interferon and Ribavirin
Authors: Nguyen Nghia H. , McCormack Shelley A. , Vutien Philip , Yee Brittany E. , Devaki Pardha , Jencks David , Nguyen Mindie H.
Published: January 2015

Objective: Our goal was to systematically and quantitatively assess treatment response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated interferon and ribavirin. Methods: We performed a literature search in MEDLINE and EMBASE for ‘genotype 6' in August 2013. Additional abstracts from major international scientific conferences from 2012 to 2013 were reviewed. Studies included were original articles with ≥10 treatment-naïve Asian HCV-6 patients. Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of 0.10 and an I2 statistic of >50%. Results of a random-effects model are reported. Results: A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12 studies were included in the analysis. The pooled sustained virologic response (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I2 = 47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001; I2 = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001). Approximately one fourth of patients without early virologic response (EVR) achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21). Conclusions: Asian patients with HCV-6 can expect higher SVR rates (∼80%) than HCV-1 patients (∼63%). EVR as a stopping rule is less clear in Asian patients with HCV-6 and HCV-1.
Percutaneous Epicardial Access for Mapping and Ablation Is Feasible in Patients With Prior Cardiac Surgery, Including Coronary Bypass Surgery
Authors: Killu Ammar M. , Ebrille Elisa , Asirvatham Samuel J. , Munger Thomas M. , McLeod Christopher J. , Packer Douglas L. , Friedman Paul A. , Mulpuru Siva K.
Published: January 2015

Background—

Prior cardiac surgery, especially the presence of coronary artery bypass grafts, is thought to preclude percutaneous epicardial access (EpiAcc) and, therefore, mapping and ablation. We evaluated the feasibility and safety of EpiAcc in patients with a prior cardiac operation.

Methods and Results—

We retrospectively analyzed all patients who underwent EpiAcc for ablation for ventricular tachycardia or symptomatic premature ventricular complexes between 2004 and 2013 at Mayo Clinic, Rochester, MN. Of 162 patients who underwent EpiAcc, 18 had prior cardiac surgery (median age, 64 years, all men). This included 10 coronary artery bypass grafts, 2 epicardial implantable cardioverter defibrillator placement, 5 valve surgery, 2 septal myectomy, 1 aortic arch replacement, 1 myocardial bridge unroofing, and 1 myocardial perforation repair (3 patients had multiple procedures). Access was successful in 12 of 18; the inferior approach was used in 78%. Successful access was achieved in 6 of 10 patients with prior coronary artery bypass grafts. Adhesiolysis was required in 10 patients with the sheath, access wire, and pigtail or ablation catheter. Intraprocedural coronary angiography was performed in 8 patients. A total of 45 ventricular tachycardias/premature ventricular complexes were ablated. Thirteen patients underwent endocardial-only ablation, 2 had epicardial-only ablation, whereas 3 had endocardial–epicardial ablation. Ablation was deemed successful in 13 of 18 patients. Four patients had bleeding complications (pericardial effusion, pericardial hematoma, hemoperitoneum, and pericardial tamponade). In patients with coronary grafts, there was no evidence of acute graft disruption.

Conclusions—

Percutaneous EpiAcc is feasible in patients with previous cardiac surgery, including coronary artery bypass grafts. However, adhesiolysis is frequently required. Although the risk of coronary graft injury is low, life-threatening complications may occur.
Survival and Neurocognitive Outcomes After Cardiac Extracorporeal Life Support in Children Less Than 5 Years of Age
Authors: Ryerson Lindsay M. , Guerra Gonzalo Garcia , Joffe Ari R. , Robertson Charlene M.T. , Alton Gwen Y. , Dinu Irina A. , Granoski Don , Rebeyka Ivan M. , Ross David B. , Lequier Laurance
Published: January 2015

Background—

Survival after pediatric cardiac extracorporeal life support (ECLS) is guarded, and neurological morbidity varies widely. Our objective is to report our 10-year experience with cardiac ECLS, including survival and kindergarten entry neurocognitive outcomes; to identify predictors of mortality or adverse neurocognitive outcomes; and to compare 2 eras, before and after 2005.

Methods and Results—

From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Sixty-four patients (65%) survived to hospital discharge, and 50 (51%) survived ≤5 years of age. Neurocognitive follow-up of survivors was completed at mean (SD) age of 52.9 (8) months using Wechsler Preschool and Primary Scale of Intelligence. Logistic regression analysis found the longer time (hours) for lactate to fall below 2 mmol/L on ECLS (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84;
P
=0.022), and the amount of platelets (mL/kg) given in the first 48 hours (hazard ratio, 1.18; 95% confidence interval, 1.06, 1.32;
P
=0.002) was independently associated with higher in-hospital mortality. Receiving ECLS after the year 2005 was independently associated with lower risk of in-hospital mortality (hazard ratio, 0.36; 95% confidence interval, 0.13, 0.99;
P
=0.048). Extracorporeal cardiopulmonary resuscitation was not independently associated with mortality or neurocognitive outcomes. Era was not independently associated with neurocognitive outcomes. The full-scale intelligence quotient of survivors without chromosomal abnormalities was 79.7 (16.6) with 25% below 2 SD of the population mean.

Conclusions—

Mortality has improved over time; time for lactate to fall on ECLS and volume of platelets transfused are independent predictors of mortality. Extracorporeal cardiopulmonary resuscitation and era were not independently associated with neurocognitive outcomes.