bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramolecular isopeptide but not internal thioester bonds confer proteolytic and significant thermal stability to the S. pyogenes pilus adhesin Spy0125
Authors: Walden Miriam , Crow Allister , Nelson Miles D. , Banfield Mark J.
Published: October 2013

Streptococcus pyogenes and other Gram‐positive bacterial pathogens present long macromolecular filaments known as pili on their surface that mediate adhesion and colonization. These pili are covalent polymers, assembled by sortases. Typically, they comprise a putative adhesin at their tip, a backbone subunit present in multiple copies and a basal subunit that is covalently anchored to the peptidoglycan layer of the cell surface. The crystal structures of pilin subunits revealed the presence of unusual covalent linkages in these proteins, including intramolecular isopeptide and internal thioester bonds. The intramolecular isopeptide bonds in backbone pilins are important for protein stability. Here, using both the wild‐type protein and a set of mutants, we assessed the proteolytic and thermal stability of the S. pyogenes pilus tip adhesin Spy0125, in the presence and absence of its intramolecular isopeptide and internal thioester bonds. We also determined a crystal structure of the internal thioester bond variant Spy0125Cys426Ala. We find that mutations in the intramolecular isopeptide bonds compromise the stability of Spy0125. Using limited proteolysis and thermal denaturation assays, we could separate the contribution of each intramolecular isopeptide bond to Spy0125 stability. In contrast, mutation in the internal thioester bond had a lesser effect on protein stability and the crystal structure is essentially identical to wild type. This work suggests that the internal thioester in Spy0125, although having a minor contributory role, is not required for protein stability and must have a different primary function, most likely mediating a covalent interaction with host cell ligands. Proteins 2014; 82:517–527. © 2013 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
Detection of peptide‐binding sites on protein surfaces: The first step toward the modeling and targeting of peptide‐mediated interactions
Authors: Lavi Assaf , Ngan Chi Ho , Movshovitz‐Attias Dana , Bohnuud Tanggis , Yueh Christine , Beglov Dmitri , Schueler‐Furman Ora , Kozakov Dima
Published: October 2013

Peptide‐mediated interactions, in which a short linear motif binds to a globular domain, play major roles in cellular regulation. An accurate structural model of this type of interaction is an excellent starting point for the characterization of the binding specificity of a given peptide‐binding domain. A number of different protocols have recently been proposed for the accurate modeling of peptide‐protein complex structures, given the structure of the protein receptor and the binding site on its surface. When no information about the peptide binding site(s) is a priori available, there is a need for new approaches to locate peptide‐binding sites on the protein surface. While several approaches have been proposed for the general identification of ligand binding sites, peptides show very specific binding characteristics, and therefore, there is a need for robust and accurate approaches that are optimized for the prediction of peptide‐binding sites. Here, we present PeptiMap, a protocol for the accurate mapping of peptide binding sites on protein structures. Our method is based on experimental evidence that peptide‐binding sites also bind small organic molecules of various shapes and polarity. Using an adaptation of ab initio ligand binding site prediction based on fragment mapping (FTmap), we optimize a protocol that specifically takes into account peptide binding site characteristics. In a high‐quality curated set of peptide‐protein complex structures PeptiMap identifies for most the accurate site of peptide binding among the top ranked predictions. We anticipate that this protocol will significantly increase the number of accurate structural models of peptide‐mediated interactions. Proteins 2013; 81:2096–2105. © 2013 Wiley Periodicals, Inc.
Protein docking using case‐based reasoning
Authors: Ghoorah Anisah W. , Devignes Marie‐Dominique , Smaïl‐Tabbone Malika , Ritchie David W.
Published: October 2013

Protein docking algorithms aim to calculate the three‐dimensional (3D) structure of a protein complex starting from its unbound components. Although ab initio docking algorithms are improving, there is a growing need to use homology modeling techniques to exploit the rapidly increasing volumes of structural information that now exist. However, most current homology modeling approaches involve finding a pair of complete single‐chain structures in a homologous protein complex to use as a 3D template, despite the fact that protein complexes are often formed from one or more domain–domain interactions (DDIs). To model 3D protein complexes by domain–domain homology, we have developed a case‐based reasoning approach called KBDOCK which systematically identifies and reuses domain family binding sites from our database of nonredundant DDIs. When tested on 54 protein complexes from the Protein Docking Benchmark, our approach provides a near‐perfect way to model single‐domain protein complexes when full‐homology templates are available, and it extends our ability to model more difficult cases when only partial or incomplete templates exist. These promising early results highlight the need for a new and diverse docking benchmark set, specifically designed to assess homology docking approaches. Proteins 2013; 81:2150–2158. © 2013 Wiley Periodicals, Inc.
Role of histidine for charge regulation of unstructured peptides at interfaces and in bulk
Authors: Kurut Anıl , Henriques João , Forsman Jan , Skepö Marie , Lund Mikael
Published: October 2013

Histidine‐rich, unstructured peptides adsorb to charged interfaces such as mineral surfaces and microbial cell membranes. At a molecular level, we investigate the adsorption mechanism as a function of pH, salt, and multivalent ions showing that (1) proton charge fluctuations are—in contrast to the majority of proteins—optimal at neutral pH, promoting electrostatic interactions with anionic surfaces through charge regulation and (2) specific zinc(II)‐histidine binding competes with protons and ensures an unusually constant charge distribution over a broad pH interval. In turn, this further enhances surface adsorption. Our analysis is based on atomistic molecular dynamics simulations, coarse grained Metropolis Monte Carlo, and classical polymer density functional theory. This multiscale modeling provides a consistent picture in good agreement with experimental data on Histatin 5, an antimicrobial salivary peptide. Biological function is discussed and we suggest that charge regulation is a significant driving force for the remarkably robust activity of histidine‐rich antimicrobial peptides. Proteins 2014; 82:657–667. © 2013 Wiley Periodicals, Inc.
Comparison of the effect of insecticides on three strains of Tyrophagus putrescentiae (Acari: Astigmata) using an impregnated filter paper test and a growth test
Authors: Stara Jitka , Nesvorna Marta , Hubert Jan
Published: October 2013

BACKGROUND

In this study, we compared the efficacy of insecticides against three strains of Tyrophagus putrescentiae using an impregnated filter paper test and a growth test. We tested the suppressive activity of commercial insecticides and their analytical standards (pirimiphos‐methyl, cypermethrin, deltamethrin, chlorfenapyr, β‐cyfluthrin).

METHODS

The strains of T. putrescentiae originated from a laboratory, a field and dog food. The mortality of the mites due to active ingredients and analytical standards was tested using an impregnated filter paper test after 24 h. Lethal doses, LD50, LD95 and LD99 were determined. A growth test was used to observe the suppressive effect of the active ingredients on mites at 21 days after application of the active ingredients to wheat grain. The effective doses ED50, ED95 and ED99 were determined, indicating the concentration at which the population was reduced by 50, 95 and 99% more than control.

RESULTS

Cypermethrin, β‐cyfluthrin and a formulation of deltamethrin with piperonylbutoxide in the pesticide K‐Othrine showed low toxicity to mites. High toxicity was observed for chlorfenapyr (LD50: 0.1–1 µg cm‐2; ED50: 0.11–1.2 µg g‐1) and pirimiphos‐methyl (LD50: 0.01–0.06 µg cm‐2; ED50: 0.2–12 µg g‐1). We did not find significant differences among the compared strains in terms of their sensitivity to highly toxic insecticides.

CONCLUSION

The obtained results showed that a filter paper test is a more sensitive method of identifying differences in pesticide susceptibility among strains, but the efficacy of pesticides against one species should be tested using a growth test. © 2013 Society of Chemical Industry
Assessment of selection and resistance risk for demethylation inhibitor fungicides in Aspergillus fumigatus in agriculture and medicine: a critical review
Authors: Gisi Ulrich
Published: October 2013

BACKGROUND

An increasing number of publications have claimed that demethylation inhibitor (DMI) fungicides are confronted with resistance development in the fungus Aspergillus fumigatus and that the origin of resistant isolates may also be outside the medical area. For resistance risk assessment and sourcing the origin of DMI resistance, the primary exposure events of A. fumigatus with DMI treatments have been analysed case by case, resulting in the pathogen exposure risk (PER).

RESULTS

The calculated maximum exposure concentrations (MEC) are highest during medical treatments (human and veterinary), certain fruit and seed treatments and wood preservation, and are much lower for crop protection applications. Most agricultural DMIs are intrinsically ∼ 10–100 times less active than medical DMIs for A. fumigatus control and potential resistance selection. However, imazalil is used in agriculture and veterinary medicine (as enilconazole) expressing strong intrinsic activity against A. fumigatus. The majority of mutations in the target gene, cyp51, of DMI‐resistant isolates are different in A. fumigatus (e.g. TR34/L98H) in comparison with plant pathogens (e.g. A379G, I381V).

CONCLUSIONS

The assumed selection risk, ASR (MEC × PER) for resistance evolution to DMIs in A. fumigatus is estimated to be highest for human and veterinary applications. However, environmental origin of DMI‐resistant spores from certain sites cannot be ruled out. © 2013 Society of Chemical Industry
Systematic chemical functionalization of hybrid molecule–surface interfaces
Authors: Caciuc V. , Lennartz M. C. , Atodiresei N. , Tsukamoto S. , Karthäuser S. , Blügel S.
Published: October 2013

In this article, we briefly overview our experimental and theoretical studies aimed to investigate the electronic structure and the transport properties of several carboxylates chemisorbed on the Cu(110) surface. In particular, we have theoretically explored the possibility to chemically functionalize a carboxylate–Cu(110) system to specifically tune its electronic structure. Experimentally, it could be proven that the transport properties of the carboxylate–Cu(110) interface indeed revealed specific features in the d spectra corresponding to the used functionalization process. Moreover, the d spectra can be used to identify specific adsorption geometries or conformations of carboxylates on Cu(110). Furthermore, transport calculations for molecules with different anchoring groups between two Cu(110) electrodes are also discussed.

Schematic view of a STM tip probing a carboxylate molecule chemisorbed on the Cu(110) surface with the corresponding energy level alignment in the case of a zero bias voltage.
DFT study of hydrogen adsorption on Eu‐decorated single‐ and double‐sided graphene
Authors: Liu Wenbo , Liu Yang , Wang Rongguo , Hao Lifeng , Song Dajun , Li Zheng
Published: October 2013

We carry out density functional theory calculations to study the adsorption of hydrogen molecules on Eu‐decorated single‐ and double‐sided graphene sheets. It is found that Eu prefers to adsorb on the hollow site of carbon ring above both the single‐ and double‐sided graphene. The hybridization of Eu on graphene is mainly between the Eu‐5d orbital and the C‐2p orbital. The charge of Eu is enhanced when the first hydrogen molecule approaches the Eu atom. As more hydrogen molecules are introduced, the charge population of Eu‐5d and 6p orbital is increased. Each Eu can stably bind up to six hydrogen molecules with an average adsorption energy of −0.404 and −0.392 eV for Eu decorated single‐ and double‐sided graphene, respectively. Eu atoms carry negative charge when 12 hydrogen molecules are attracted by the Eu‐decorated double‐sided graphene. The main interaction between hydrogen and Eu is similar to Kubas binding, which contains hybridization of H–σ* and Eu‐5d orbital and charge transfer between them.
Transient thermal response of an individual multiwall carbon nanotube
Authors: Wada Yukiko , Ohshima Yusuke , Arie Takayuki , Akita Seiji
Published: October 2013

We have proposed a method for measuring the transient thermal response of an individual carbon nanotube under Joule heating with pulse current. A transient temperature response with a time constant of about 50 ns was measured. A simplified lumped capacitance model revealed that this fast response corresponds to the small heat capacity of the nanotube. The measured transient response was fairly well reproduced by finite element method analysis using parameters of bulk graphite, which indicates that the bulk graphite parameters are compatible with those of well‐graphitized nanotubes. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Design of new carbon allotropes of fused small fullerenes
Authors: Maruyama Mina , Okada Susumu
Published: October 2013

We have designed novel two‐dimensional (2D) carbon allotropes consisting of the small fullerene C26 using first‐principles total energy calculations based on the density functional theory. We found that the fused C26 polyhedra form a periodic 2D honeycomb covalent net‐work. The initial honeycomb network converted into two different stable structures upon structural optimization.

Both phases were found to be energetically stable, and the calculated total energies were found to be 0.6 eV/atom higher than the energy of diamond. The electronic structures of the two fused C26 networks were found to be metals, and one of the structures possesses linear dispersion bands near the Fermi level, owing to the formation of a one‐dimensional fused octagonal sp2 network on the polymeric layer. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the possibility of sub 60 mV/decade subthreshold switching in piezoelectric gate barrier transistors
Authors: Jana Raj K. , Snider Gregory L. , Jena Debdeep
Published: October 2013

A novel method for the reduction of subthreshold slope below the room‐temperature Boltzmann limit of 60 mV/dec for a field‐effect transistor based on negative differential capacitance is proposed. This effect uses electric field induced electrostriction of a piezoelectric gate barrier of the transistor. The mechanism amplifies the internal surface potential over the applied gate voltage. This internal voltage gain mechanism provides an opportunity for steep subthreshold slope switching below 60 mV/decade of the transistor current. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermoelectricity in semiconductor nanowires
Authors: Kim Jungwon , Bahk Je‐Hyeong , Hwang Junphil , Kim Hoon , Park Hwanjoo , Kim Woochul
Published: October 2013

magnified image

In this paper, we provide a comprehensive review on recent advances in the development of semiconductor nanowires for thermoelectric energy conversion. Semiconductor nanowires can exhibit novel properties in the electron and phonon transport as their diameters approach the characteristic length scales of the material such as the electron wavelength and the phonon mean free path. These size effects in semiconducting nanowires are discussed as a means to enhance the thermoelectric properties of the nanowires over their bulk counterparts. Challenges for the enhancement are also identified. We present recent theoretical and experimental results on various thermoelectric nanowires including Si, Ge, InAs, Bi, Bi–Te and Bi–Sb nanowires. Various characterization techniques for the accurate electrical and thermal measurements of individual nanowires are also covered. Finally, we mention briefly the recent efforts to fabricate thermoelectric devices using nanowire arrays. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Insertion of fullerene layer for bulk heterojunction organic photovoltaic cell fabricated by electrospray deposition method
Authors: Fukuda Takeshi , Takagi Kenji , Liao Yingjie
Published: October 2013

An improved power conversion efficiency (PCE) of bulk heterojunction organic photovoltaic cell (OPV) was achieved by inserting an n‐type [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM) layer between the active layer and a metal electrode. The controlled substrate temperature was found to be a useful parameter for the multilayer structure (active layer/ PCBM) by the electrospray deposition method. Under optimized substrate temperature during the PCBM deposition, a multilayer structure could be formed, and the PCE was improved up to 1.94%.

magnified image

(© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The ULF/ELF electromagnetic radiation before the 11 March 2011 Japanese earthquake
Authors: Ohta K. , Izutsu J. , Schekotov A. , Hayakawa M.
Published: October 2013

The ULF/ELF short‐term electromagnetic precursor is discovered for the disastrous Japan earthquake (EQ) occurred on 11 March 2011. This analysis is based on the records measured by search coil magnetometers located at Nakatsugawa (geographic coordinates; 35.42°N, 137.55°E), Shinojima (34.67°N, 137.01°E), and Izu (34.64°N, 137.01°E) of the Chubu University network. The data of these magnetometers are extensively used to analyze the ULF/ELF seismo‐atmospheric radiation. It is then found that the ULF/ELF atmospheric radio emission is reliably detected on 6 March before the main shock on 11 March, probably as a precursory signature of the EQ. Further confirmation on its seismic origin was provided by the observational fact that the azimuths of the radiation source from all observation sites coincide approximately with the region of the forthcoming EQ.
Characteristics of M‐component in rocket‐triggered lightning and a discussion on its mechanism
Authors: Jiang Rubin , Qie Xiushu , Yang Jing , Wang Caixia , Zhao Yang
Published: October 2013

The current and electric field pulses associated with M‐component following dart leader‐return stroke sequences in negative rocket‐triggered lightning flashes were analyzed in detail by using the data from Shandong Artificially Triggering Lightning Experiment, conducted from 2005 to 2010. For 63 M‐components with current waveforms superimposed on the relatively steady continuing current, the geometric mean values of the peak current, duration, and charge transfer were 276 A, 1.21 ms, and 101 mC, respectively. The behaviors of the channel base current versus close electric field changes and the observation facts by different authors were carefully examined for investigation on mechanism of the M‐component. A modified model based on Rakov's “two‐wave” theory is proposed and confirms that the evolution of M‐component through the lightning channel involves a downward wave transferring negative charge from the upper to the lower channel and an upward wave draining the charge transported by the downward wave. The upward wave serves to deplete the negative charge by the downward wave at its interface and makes the charge density of the channel beneath the interface layer to be roughly zero. Such modified concept is recognized to be reasonable by the simulated results showing a good agreement between the calculated and the measured E‐field waveforms.
A new continuous high‐gain controller scheme for a class of uncertain nonlinear systems
Authors: Dasdemir Janset , Zergeroglu Erkan
Published: October 2013

In this study, we present a new robust continuous controller mechanism for the tracking problem of uncertain nonlinear systems. The proposed strategy is based on a Lyapunov‐type stability argument and only requires the uncertainties of the dynamical system to be the first‐order differentiable to achieve asymptotic practical tracking. For the ease of presentation, the controller formulation is presented on a general, second‐order dynamical system, extension to higher order versions are also possible with a considerably small effort. Simulation studies comparing the performance of the proposed method with the classical Sliding mode and robust integral of the sign of the error controller are presented to illustrate the performance and the feasibility of the proposed strategy. Experimental validation on a two link direct drive robot manipulator are also included to illustrate the implementability of the proposed method. Copyright © 2013 John Wiley & Sons, Ltd.
Model predictive control of directed‐graph constrained systems
Authors: Kobayashi Koichi , Imura Jun‐ichi , Matsushima Hiromichi
Published: October 2013

This paper addresses a new type of model predictive control problem for a hybrid system that consists of a continuous‐time linear system and a temporal/spatial directed graph, called a directed‐graph constrained system. Motivated by the obstacle avoidance problem, the problem is newly formulated, where the continuous‐time control input and the waypoints of the state are simultaneously optimized under a temporal/spatial directed graph as well as input/state linear constraints, and a method for efficiently solving this problem is developed. Numerical examples are presented to verify that the proposed approach is effective. Copyright © 2013 John Wiley & Sons, Ltd.
Reachable set estimation for discrete‐time linear systems with time delays
Authors: Lam James , Zhang Baoyong , Chen Yong , Xu Shengyuan
Published: October 2013

This paper is concerned with the reachable set estimation problem for discrete‐time linear systems with multiple constant delays and bounded peak inputs. The objective is to check whether there exists a bounded set that contains all the system states under zero initial conditions. First, delay‐dependent conditions for the solvability of the addressed problem are derived by employing a novel Lyapunov–Krasovskii functional. The obtained conditions are expressed in terms of matrix inequalities, which are linear when only one scalar variable is fixed. On the basis of these conditions, an ellipsoid containing the reachable set of the considered system is obtained. An approach for determining the smallest ellipsoid is also provided. Second, the approach and results developed in the first stage are generalized to the case of systems with polytopic parameter uncertainties, and delay‐dependent conditions are given in the form of relaxed matrix inequalities. Finally, two numerical examples are provided to demonstrate the effectiveness of the proposed methods. Copyright © 2013 John Wiley & Sons, Ltd.
SPARTAN: Developing a Vision System for Future Autonomous Space Exploration Robots
Authors: Kostavelis Ioannis , Nalpantidis Lazaros , Boukas Evangelos , Rodrigalvarez Marcos Aviles , Stamoulias Ioannis , Lentaris George , Diamantopoulos Dionysios , Siozios Kostas , Soudris Dimitrios , Gasteratos Antonios
Published: October 2013

Mars exploration is expected to remain a focus of the scientific community in the years to come. A Mars rover should be highly autonomous because communication between the rover and the terrestrial operation center is difficult, and because the vehicle should spend as much of its traverse time as possible moving. Autonomous behavior of the rover implies that the vision system provides both a wide view to enable navigation and three‐dimensional (3D) reconstruction, and at the same time a close‐up view ensuring safety and providing reliable odometry data. The European Space Agency funded project “SPAring Robotics Technologies for Autonomous Navigation” (SPARTAN) aimed to develop an efficient vision system to cover all such aspects of autonomous exploratory rovers. This paper presents the development of such a system, starting from the requirements up to the testing of the working prototype. The vision system was designed with the intention of being efficient, low‐cost, and accurate and to be implemented using custom‐designed vectorial processing by means of field programmable gate arrays (FPGAs). A prototype of the complete vision system was developed, mounted on a basic mobile robot platform, and tested. The results on both real‐world Mars‐like and long‐range simulated data are presented in terms of 3D reconstruction and visual odometry accuracy, as well as execution speed. The developed system is found to fulfill the set requirements.
A review of climatic controls on δ18O in precipitation over the Tibetan Plateau: Observations and simulations
Authors: Yao Tandong , Masson‐Delmotte Valerie , Gao Jing , Yu Wusheng , Yang Xiaoxin , Risi Camille , Sturm Christophe , Werner Martin , Zhao Huabiao , He You , Ren Wei , Tian Lide , Shi Chunming , Hou Shugui
Published: October 2013

The stable oxygen isotope ratio (δ18O) in precipitation is an integrated tracer of atmospheric processes worldwide. Since the 1990s, an intensive effort has been dedicated to studying precipitation isotopic composition at more than 20 stations in the Tibetan Plateau (TP) located at the convergence of air masses between the westerlies and Indian monsoon. In this paper, we establish a database of precipitation δ18O and use different models to evaluate the climatic controls of precipitation δ18O over the TP. The spatial and temporal patterns of precipitation δ18O and their relationships with temperature and precipitation reveal three distinct domains, respectively associated with the influence of the westerlies (northern TP), Indian monsoon (southern TP), and transition in between. Precipitation δ18O in the monsoon domain experiences an abrupt decrease in May and most depletion in August, attributable to the shifting moisture origin between Bay of Bengal (BOB) and southern Indian Ocean. High‐resolution atmospheric models capture the spatial and temporal patterns of precipitation δ18O and their relationships with moisture transport from the westerlies and Indian monsoon. Only in the westerlies domain are atmospheric models able to represent the relationships between climate and precipitation δ18O. More significant temperature effect exists when either the westerlies or Indian monsoon is the sole dominant atmospheric process. The observed and simulated altitude‐δ18O relationships strongly depend on the season and the domain (Indian monsoon or westerlies). Our results have crucial implications for the interpretation of paleoclimate records and for the application of atmospheric simulations to quantifying paleoclimate and paleo‐elevation changes.
NOVEL AQUATIC ECOSYSTEMS: THE NEW REALITY FOR STREAMS IN CALIFORNIA AND OTHER MEDITERRANEAN CLIMATE REGIONS
Authors: Moyle P. B.
Published: October 2013

Temporary streams in California and other Mediterranean climate areas are among the aquatic habitats most altered by human actions and by invasions by alien species. They typically support novel ecosystems, defined as ecosystems dominated by new combinations of organisms in highly altered habitats. Although these new ecosystems have many attributes of the ecosystems they replaced, such as native species, they typically contain many new interactions among species. Managers need to recognize this reality to find ways to direct change towards novel ecosystems with desirable features, including native species. The concept of reconciliation ecology is a practical approach to living with the new reality; it includes actively guiding ecosystem change, as illustrated by Putah Creek, Cosumnes River, Eel River and Six Bit Gulch in California. The first three waterways are all highly altered and managed with varying degrees of success to favour desired aquatic species, whereas Six Bit Gulch experiences such extreme conditions that the original ecosystem is still largely intact. The examples illustrate that most aquatic ecosystems in California are so highly altered that attempting to restore them to an earlier condition or stable state is largely not possible. Where more or less intact systems persist, it is usually because extreme environmental conditions restrict both alien invaders and human use in small watersheds. This pattern appears to be fairly typical of streams in Mediterranean climate areas. Copyright © 2013 John Wiley & Sons, Ltd.
A secure K‐automorphism privacy preserving approach with high data utility in social networks
Authors: Yang Jun , Wang Bin , Yang Xiaochun , Zhang Hongyi , Xiang Guang
Published: October 2013

The prevalence of social networks has raised the concern for individual privacy leakage. Although preserving user privacy in social networks has been studied extensively, there is still a lot of room for improvement in the state of the art techniques. For example, the recently proposed K‐automorphism model can prevent node identity attack by constructing a K‐automorphism graph; however, it ignores preserving the privacy of the edges, resulting in path length leakage and edge leakage in the anonymous graph. Another example is the K‐isomorphism model, which was proposed to improve the K‐automorphism model by transforming the graph of social networks into K disjoined isomorphic subgraphs. However, it cuts off the connection among subgraphs, which impairs the data utility of the released anonymous graph. In this paper, we design a secure and high utility privacy preserving model, called AK‐secure, to prevent node identity attack, path length leakage, and edge leakage effectively. On the basis of the AK‐secure privacy preserving model, we propose a graph anonymous algorithm, which constructs an anonymous graph satisfying the AK‐secure privacy preserving model, minimizing information loss and guaranteeing high data utility. Extensive experiments on real data sets show the security, effectiveness of our AK‐secure privacy preserving model and the high data utility of the released anonymous graph. Copyright © 2013 John Wiley & Sons, Ltd.
Anomaly diagnosis based on regression and classification analysis of statistical traffic features
Authors: Liu Lei , Jin Xiaolong , Min Geyong , Xu Li
Published: October 2013

Traffic anomalies caused by Distributed Denial‐of‐Service (DDoS) attacks are major threats to both network service providers and legitimate customers. The DDoS attacks regularly consume and exhaust the resources of victims and hence result in abnormal bursty traffic through end‐user systems. Additionally, malicious traffic aggregated into normal traffic often show dramatic changes in the traffic nature and statistical features. This study focuses on early detection of traffic anomalies caused by DDoS attacks in light of analyzing the network traffic behavior. Key statistical features including variance, autocorrelation, and self‐similarity are employed to characterize the network traffic. Further, artificial neural network and support vector machine subject to the performance metrics are employed to predict and classify the abnormal traffic. The proposed diagnosis mechanism is validated through experiments where the datasets consist of two groups. The first group is the Massachusetts Institute of Technology Lincoln Laboratory dataset containing labeled DoS attack. The second group collected from DDoS attack simulation experiments covers three representative traffic shapes resulting from the dynamic attack rate configuration, namely, constant intensity, ramp‐up behavior, and pulsing behavior. The experimental results demonstrate that the developed mechanism can effectively and precisely alert the abnormal traffic within short response period. Copyright © 2013 John Wiley & Sons, Ltd.
The use of propensity score methods with survival or time‐to‐event outcomes: reporting measures of effect similar to those used in randomized experiments
Authors: Austin Peter C.
Published: October 2013

Propensity score methods are increasingly being used to estimate causal treatment effects in observational studies. In medical and epidemiological studies, outcomes are frequently time‐to‐event in nature. Propensity‐score methods are often applied incorrectly when estimating the effect of treatment on time‐to‐event outcomes. This article describes how two different propensity score methods (matching and inverse probability of treatment weighting) can be used to estimate the measures of effect that are frequently reported in randomized controlled trials: (i) marginal survival curves, which describe survival in the population if all subjects were treated or if all subjects were untreated; and (ii) marginal hazard ratios. The use of these propensity score methods allows one to replicate the measures of effect that are commonly reported in randomized controlled trials with time‐to‐event outcomes: both absolute and relative reductions in the probability of an event occurring can be determined. We also provide guidance on variable selection for the propensity score model, highlight methods for assessing the balance of baseline covariates between treated and untreated subjects, and describe the implementation of a sensitivity analysis to assess the effect of unmeasured confounding variables on the estimated treatment effect when outcomes are time‐to‐event in nature. The methods in the paper are illustrated by estimating the effect of discharge statin prescribing on the risk of death in a sample of patients hospitalized with acute myocardial infarction. In this tutorial article, we describe and illustrate all the steps necessary to conduct a comprehensive analysis of the effect of treatment on time‐to‐event outcomes. © 2013 The authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
Power calculation for overall hypothesis testing with high‐dimensional commensurate outcomes
Authors: Chi Yueh‐Yun , Gribbin Matthew J. , Johnson Jacqueline L. , Muller Keith E.
Published: October 2013

The complexity of system biology means that any metabolic, genetic, or proteomic pathway typically includes so many components (e.g., molecules) that statistical methods specialized for overall testing of high‐dimensional and commensurate outcomes are required. While many overall tests have been proposed, very few have power and sample size methods. We develop accurate power and sample size methods and software to facilitate study planning for high‐dimensional pathway analysis. With an account of any complex correlation structure between high‐dimensional outcomes, the new methods allow power calculation even when the sample size is less than the number of variables. We derive the exact (finite‐sample) and approximate non‐null distributions of the ‘univariate’ approach to repeated measures test statistic, as well as power‐equivalent scenarios useful to generalize our numerical evaluations. Extensive simulations of group comparisons support the accuracy of the approximations even when the ratio of number of variables to sample size is large. We derive a minimum set of constants and parameters sufficient and practical for power calculation. Using the new methods and specifying the minimum set to determine power for a study of metabolic consequences of vitamin B6 deficiency helps illustrate the practical value of the new results. Free software implementing the power and sample size methods applies to a wide range of designs, including one group pre‐intervention and post‐intervention comparisons, multiple parallel group comparisons with one‐way or factorial designs, and the adjustment and evaluation of covariate effects. Copyright © 2013 John Wiley & Sons, Ltd.
Traditional multiplicity adjustment methods in clinical trials
Authors: Dmitrienko Alex , D'Agostino Ralph
Published: October 2013

This tutorial discusses important statistical problems arising in clinical trials with multiple clinical objectives based on different clinical variables, evaluation of several doses or regiments of a new treatment, analysis of multiple patient subgroups, etc. Simultaneous assessment of several objectives in a single trial gives rise to multiplicity. If unaddressed, problems of multiplicity can undermine integrity of statistical inferences. The tutorial reviews key concepts in multiple hypothesis testing and introduces main classes of methods for addressing multiplicity in a clinical trial setting. General guidelines for the development of relevant and efficient multiple testing procedures are presented on the basis of application‐specific clinical and statistical information. Case studies with common multiplicity problems are used to motivate and illustrate the statistical methods presented in the tutorial, and software implementation of the multiplicity adjustment methods is discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Visualizing the flow of evidence in network meta‐analysis and characterizing mixed treatment comparisons
Authors: König Jochem , Krahn Ulrike , Binder Harald
Published: October 2013

Network meta‐analysis techniques allow for pooling evidence from different studies with only partially overlapping designs for getting a broader basis for decision support. The results are network‐based effect estimates that take indirect evidence into account for all pairs of treatments. The results critically depend on homogeneity and consistency assumptions, which are sometimes difficult to investigate. To support such evaluation, we propose a display of the flow of evidence and introduce new measures that characterize the structure of a mixed treatment comparison. Specifically, a linear fixed effects model for network meta‐analysis is considered, where the network estimates for two treatments are linear combinations of direct effect estimates comparing these or other treatments. The linear coefficients can be seen as the generalization of weights known from classical meta‐analysis. We summarize properties of these coefficients and display them as a weighted directed acyclic graph, representing the flow of evidence. Furthermore, measures are introduced that quantify the direct evidence proportion, the mean path length, and the minimal parallelism of mixed treatment comparisons. The graphical display and the measures are illustrated for two published network meta‐analyses. In these applications, the proposed methods are seen to render transparent the process of data pooling in mixed treatment comparisons. They can be expected to be more generally useful for guiding and facilitating the validity assessment in network meta‐analysis. Copyright © 2013 John Wiley & Sons, Ltd.
Incorporating adverse event relatedness into dose‐finding clinical trial designs
Authors: Darssan Darsy , Thompson Mery H. , Pettitt Anthony N.
Published: October 2013

Dose‐finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose‐level estimation. We incorporate adverse event relatedness into the so‐called continual reassessment method. Adverse events that have ‘doubtful’ or ‘possible’ relationships to the drug are modelled using a two‐parameter logistic model with an additive probability mass. Adverse events ‘probably’ or ‘definitely’ related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies. Copyright © 2013 John Wiley & Sons, Ltd.
Identifiability of subgroup causal effects in randomized experiments with nonignorable missing covariates
Authors: Ding Peng , Geng Zhi
Published: October 2013

Although randomized experiments are widely regarded as the gold standard for estimating causal effects, missing data of the pretreatment covariates makes it challenging to estimate the subgroup causal effects. When the missing data mechanism of the covariates is nonignorable, the parameters of interest are generally not pointly identifiable, and we can only get bounds for the parameters of interest, which may be too wide for practical use. In some real cases, we have prior knowledge that some restrictions may be plausible. We show the identifiability of the causal effects and joint distributions for four interpretable missing data mechanisms and evaluate the performance of the statistical inference via simulation studies. One application of our methods to a real data set from a randomized clinical trial shows that one of the nonignorable missing data mechanisms fits better than the ignorable missing data mechanism, and the results conform to the study's original expert opinions. We also illustrate the potential applications of our methods to observational studies using a data set from a job‐training program. Copyright © 2013 John Wiley & Sons, Ltd.
On the estimation of the reproduction number based on misreported epidemic data
Authors: Azmon Amin , Faes Christel , Hens Niel
Published: October 2013

Epidemic data often suffer from underreporting and delay in reporting. In this paper, we investigated the impact of delays and underreporting on estimates of reproduction number. We used a thinned version of the epidemic renewal equation to describe the epidemic process while accounting for the underlying reporting system. Assuming a constant reporting parameter, we used different delay patterns to represent the delay structure in our model. Instead of assuming a fixed delay distribution, we estimated the delay parameters while assuming a smooth function for the reproduction number over time. In order to estimate the parameters, we used a Bayesian semiparametric approach with penalized splines, allowing both flexibility and exact inference provided by MCMC. To show the performance of our method, we performed different simulation studies. We conducted sensitivity analyses to investigate the impact of misspecification of the delay pattern and the impact of assuming nonconstant reporting parameters on the estimates of the reproduction numbers. We showed that, whenever available, additional information about time‐dependent underreporting can be taken into account. As an application of our method, we analyzed confirmed daily A(H1N1) v2009 cases made publicly available by the World Health Organization for Mexico and the USA. Copyright © 2013 John Wiley & Sons, Ltd.
Capsular Contraction with S-Shaped Deformity of Nonlength-Expanding Inflatable Penile Prosthesis Cylinders: Management and Prevention Strategies
Authors: Karpman Edward , Henry Gerard
Published: October 2013

Introduction

Capsular contraction (CC) occurring with inflatable penile prosthesis (IPP) reservoirs has been reported by urologists as a cause of autoinflation. The concept of CC occurring around IPP cylinders has not been studied.

Aims

Herein we report a case of CC occurring with nonlength-expanding IPP cylinders, resulting in an S-shaped deformity.

Main Outcome Measures

We sought to report a novel cause of S-shaped deformity in patients after IPP surgery.

Methods

We reviewed a recent clinical case and conducted a literature review on capsular scar formation in prosthetic surgery. We also conducted a literature review of the inflammatory cascade related with prosthetic surgery.

Results

Capsular contracture of nonlength-expanding cylinders resulting in S-shaped deformity has not been previously reported. The role of certain inflammatory markers seems to play a common role of capsular contracture in the penis and other prosthetic implantation sites.

Conclusions

Capsular contractures around the cylinders of an IPP can cause deformity, even in patients who have appropriately sized, nonlength-expanding cylinders. A better understanding is needed regarding the mechanical properties of the tunica albuginea and the inflammatory cascade associated with penile implant surgery. This case represents an argument for early and aggressive postoperative inflation of the IPP. Future studies should evaluate the role of inflammation modulators as adjuvant therapy after IPP surgery.
In Situ Electron Microscopy Four‐Point Electromechanical Characterization of Freestanding Metallic and Semiconducting Nanowires
Authors: Bernal Rodrigo A. , Filleter Tobin , Connell Justin G. , Sohn Kwonnam , Huang Jiaxing , Lauhon Lincoln J. , Espinosa Horacio D.
Published: October 2013

Electromechanical coupling is a topic of current interest in nanostructures, such as metallic and semiconducting nanowires, for a variety of electronic and energy applications. As a result, the determination of structure‐property relations that dictate the electromechanical coupling requires the development of experimental tools to perform accurate metrology. Here, a novel micro‐electro‐mechanical system (MEMS) that allows integrated four‐point, uniaxial, electromechanical measurements of freestanding nanostructures in‐situ electron microscopy, is reported. Coupled mechanical and electrical measurements are carried out for penta‐twinned silver nanowires, their resistance is identified as a function of strain, and it is shown that resistance variations are the result of nanowire dimensional changes. Furthermore, in situ SEM piezoresistive measurements on n‐type, [111]‐oriented silicon nanowires up to unprecedented levels of ∼7% strain are demonstrated. The piezoresistance coefficients are found to be similar to bulk values. For both metallic and semiconducting nanowires, variations of the contact resistance as strain is applied are observed. These variations must be considered in the interpretation of future two‐point electromechanical measurements.
In Vivo Immune Cell Distribution of Gold Nanoparticles in Naïve and Tumor Bearing Mice
Authors: Almeida Joao Paulo Mattos , Lin Adam Yuh , Langsner Robert James , Eckels Phillip , Foster Aaron Edward , Drezek Rebekah Anna
Published: October 2013

Gold nanoparticles (AuNP) have been widely used for drug delivery and have recently been explored for applications in cancer immunotherapy. Although AuNPs are known to accumulate heavily in the spleen, the particle distribution within immune cells has not been thoroughly studied. Here, cellular distribution of Cy5 labeled 50 nm AuNPs is characterized within the immune populations of the spleen from naïve and tumor bearing mice using flow cytometry. Surprisingly, approximately 30% of the detected AuNPs are taken up by B cells at 24 h, with about 10% in granulocytes, 18% in dendritic cells, and 8% in T cells. In addition, 3% of the particles are detected within myeloid derived suppressor cells, an immune suppressive population that could be targeted for cancer immunotherapy. Furthermore, it is observed that, over time, the particles traveled from the red pulp and marginal zone to the follicles of the spleen. Taking into consideration that the particle cellular distribution does not change at 1, 6 and 24 h, it is highly suggestive that the immune populations carry the particles and migrate through the spleen instead of the particles migrating through the tissue by cell‐cell transfer. Finally, no difference is observed in particle distribution between naïve and tumor bearing mice in the spleen, and nanoparticles are detected within 0.7% of dendritic cells of the tumor microenvironment. Overall, these results can help inform and influence future AuNP delivery design criteria including future applications for nanoparticle‐mediated immunotherapy.