bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Identity-Based Multi-Signcryption Scheme
Authors: Zhang Jianhong , Yang Yixian , Niu Xinxin
Published: January 2009

Message security and the sender's identity authentication for communication in the open channel is a basic and important technology of the internet. For keeping the message confidential and unforgeable, the sender can use a digital signature algorithm with his private key to sign the message, and then encrypts the signature on the message. Signcryption which was proposed by Zheng et. al in 1997 is a novel cryptographic primitive that simultaneously provides the authentication and encryption in a single logic step and at lower computational costs and communication overheads than the above sign-then-encrypt way. Since then, there are many signcryption schemes proposed. Only recently, a formal security proof model is formalized providing security proof for Zheng's signcryption in the random oracle model. In the ID-based cryptography, the complexity of the managing certificate is reduced.

In this work, by combining a multisignature with an ID-based signcryption scheme, we build a security model of multi-signcryption to define confidentiality and unforgeability of the ID-based signcryption scheme and have proposed an ID-based multi-signcryption scheme based on the bilinear pairings to adapt to a multi-user setting. Given a message m, a receiver's identity IDB, and n sender's identities IDA1, IDA2, …, IDAn, for each sender Ai, it executes the followings steps: randomly pick xi ε Zq to compute Ri = xiP and ω = xiQIDB; send (Ri, ωi) to the other senders by a secure channel; (3)after receiving the other senders (Ri, ωi), Ai computes ω = e(Ppub, Σωj) to set c = H2(ω)⊕m and R = ΣRj; compute Si = xiH4(m) + H3(R,ω)SIDAi, where SIDAi is the private key of sender Ai.

Then the resulting ciphertext is (c,S,R). To unsigcrypt the ciphertext (c,S,R) in the sender list L = (IDA1, IDA2, …, IDAn), the receiver with identity IDB can compute the following steps to recover and verify the message validity. compute ω = e(R,SIDB) and m = H2(ω)⊕c, where SIDB is private key of the receiver; accept the message if and only if the following equation holds [Formula: see text]

By security analysis, we show that our scheme satisfies the two important properties of signcryption: confidentiality and unforgeability, and is proven to have been secure in the random oracle model. The security of the scheme is closely related to the Decisional Bilinear Diffie-Hellman assumption and the computational Diffie-Hellman assumption. Finally, by analyzing the efficiency of the scheme, we show that our scheme is very efficient, and only one pairing computation is needed in the signcryption phase, three pairing operators are needed in the unsigncrytion phase, and the ciphertext size is about 420 bits.
Ant-Based Reliable Multi-Constrained Anycast Routing for Sensor Networks
Authors: Yu Jianping , Lin Yaping , Wang Yong
Published: January 2009

Wireless sensor networks (WSNs) are task-specific where the tasks are specified by the users or applications. Energy and delay constraints have had a great impact on the design and operation of the WSNs. As routing plays an important role in data-centric WSNs, there are numerous energy aware routing protocols proposed for WSNs with single sink, generally using multi-hop paths to use the energy more efficiently. But most of them do not consider the communication delay carefully. As many applications of WSNs require real-time communication, the end-to-end delivery delay is another point to be considered, especially for urgent events. When considering the multiple QoS constraints such as the delivery delay and the minimal energy required, the multi-constrained routing is NP-hard.

Moreover, WSNs also suffer from a scalability problem as the total number of nodes can reach hundreds or thousands. Thus, sensors located near the sink consume large amounts of energy. The sink is then isolated once they deplete their batteries, and the network fails to function. To cope with the scalability problem, multi-sink configuration is adopted for large-scale WSNs. How to select the optimum sink for packets with different delay and energy constraints in large-scale WSNs is the main problem to be resolved in this paper, which is called the multi-constrained anycast (MCA) problem. Obviously, it is NP-hard.

We investigate the MCA problem in resource-constrained WSNs with multiple sinks and two-tier architecture, where the source cluster-heads send collected data to only one optimum sink. To reduce the energy consumption and shorten the delivery delay, a distributed anycast algorithm ARMCA inspired by swarm intelligence of ants is proposed, which can also achieve reliable data gathering during the deployment period. The scheme takes advantage of beneficial clustering and routing emerging in a self-organized way from the positive interaction of ants. The idea of the ACO-based routing is adopted to achieve the good performance of energy-efficiency and delivery delay. Meanwhile, the ant-based clustering is utilized to ensure the reliability. By the combination of the ant-based routing and clustering models, the ARMCA protocol can solve the MCA problem efficiently and flexibly.

The simulation results demonstrated that the proposed algorithm can reliably deliver collected events to the optimum sinks efficiently, and has self-recovery capabilities to deal with failures of sensors including the sinks. Not only is the energy cost reduced, but also the delivery delay is shortened significantly when transmitting packets of the named events to the sinks.
The Modeling and the Sensor Fault Diagnosis of a Continuous Stirred Tank Reactor with a Takagi-Sugeno Recurrent Fuzzy Neural Network
Authors: Shi Li , Wang Lijia , Wang Zhizhong
Published: January 2009

In this paper, a novel Takagi-Sugeno recurrent fuzzy neural network (TSRFNN) is constructed for modeling and sensor fault diagnosis of a Continuous Stirred Tank Reactor (CSTR), a nonlinear dynamic system. The TSRFNN is composed of 9 layers, including premise network and consequence network. The temporal information is embedded in the TSRFNN by adding the feedback connections between the output layer and the input layer of the fuzzy neural network (FNN). It is assumed that the inputs are Gaussian membership functions; the product operation is utilized for the premise and implication, and the weighted center-average method is adopted for defuzzification. The network is a Fuzzy Basis Function(FBF). The general approximation characteristic of the network was proven by the theory reasoning. The identification of the TSRFNN consists of two steps: structure identification and parameter identification. Unsupervised clustering is used to determine the structure of the fuzzy system, the number of fuzzy rules, and the membership functions of the premise using the input-output data of a system. Then in the parameter identification, the Dynamic Backpropagation (DBP) is adopted to determine the membership functions of the conclusion of the fuzzy system.

Then the network is applied to the modeling and diagnosis of a CSTR system. The network is applied to set up the sensors models of a CSTR system, including the models of the temperature sensor faults and the models of concentration sensor faults. To set up a high performance diagnosis model, a persistent signal was chosen to sufficiently activate the plant. Finally an Adaptive Threshold Algorithm based on statistics is used to fault diagnose. If there are sensor faults in the CSTR, the bias between the actual output of the plant and the output of the network surpasses the threshold and the faults are detected on-line according to it. The effectiveness of the modeling and diagnosis approach proposed was verified by the simulation results with Matlab.

Therefore, the proposed network and the fault diagnosis approach can be employed to a CSTR system successfully and be extended to the modeling and fault detection of other nonlinear systems.
A Reputation System with Anti-Pollution Mechanism in P2P File Sharing Systems
Authors: Mei Qi , Yajun Guo , Huifang Yan
Published: January 2009

File pollution has become a very serious problem in peer-to-peer file sharing systems, because of which it greatly reduces the effectiveness of systems. Users downloaded pollution files not only consumed bandwidth, but were also likely to share polluted files without checking. If these polluted files carry a virus, Trojan horse, or other malicious code, the loss of users would be disastrous. There is much research done on reputation-based anti-pollution mechanisms. Peer reputation systems and object reputation systems are two representatives reputation-based anti-pollution mechanisms currently. Peer reputation systems only care about the reputation of file providers, while object reputation systems only care about the reputation of sharing files. This paper proposes an anti-pollution mechanism combined with peer reputation and object reputation. Different from former research, we calculate the reputation of sharing files by the reputation of the voting peer. That is, object reputation is weighted by peer reputation. The reputation of the voting peer is built by its direct trust value and recommended trust value. Direct trust considers the trust of Direct Interaction Experience and the trust of Voting Similar Experience. Severe penalty strategy and voting incentive mechanism are introduced in calculating direct trust value. Therefore, a good user who uploads unpolluted files and voting on files actively can have a higher reputation, while a malicious user who uploads polluted files or voting unhonestly would have his reputation reduced sharply. Our expectation is that users for their own reputation will delect polluted files as soon as possible. These strategies give users an incentive to awareness of pollution, consequently isolate the polluters effectively. Our reputation mechanism is intended to prevent pollution spread by stimulating the awareness of users to delete files as soon as possible. At last, we simulate a P2P file sharing system to assess our reputation mechanism. The simulation results show that, compared to the object reputation system, our reputation mechanism convergence is faster, and has a better anti-pollution performance.
Min-Min Chromosome Genetic Algorithm for Load Balancing in Grid Computing
Authors: Shu Wanneng , Wang Jiangqing
Published: January 2009

Load balancing is a very important and complex problem in grid computing. This paper studies Min-min chromosome genetic algorithm (MCGA) to gauge their suitability for solving grid load balancing problems. The effectiveness of the MCGA algorithm is shown for a number of test problems. Performance comparisons with Min-min, and genetic algorithm are also discussed.
Quantum-Inspired Genetic Algorithm Based on Simulated Annealing for Combinatorial Optimization Problem
Authors: Shu Wanneng
Published: January 2009

Quantum-inspired genetic algorithm (QGA) is applied to simulated annealing (SA) to develop a class of quantum-inspired simulated annealing genetic algorithm (QSAGA) for combinatorial optimization. With the condition of preserving QGA advantages, QSAGA takes advantage of the SA algorithm so as to avoid premature convergence. To demonstrate its effectiveness and applicability, experiments are carried out on the knapsack problem. The results show that QSAGA performs well, without premature convergence as compared to QGA.
A RM-Based Static Deployment System for Cluster
Authors: Wu Weiguo , Zhang Leiqiang , Wang Lei , Xue Zhenghua
Published: January 2009

In this paper, a Reliable-Multicast (RM) based static deployment system for cluster is designed which can be functionally divided into three parts: image capture, image transference, and node configuration. Image capture takes the snapshot of the operating system in the source node. Image transference distributes the captured image to target nodes. Node configuration mainly finishes the configuration of some identified information to target nodes.

Applying the technology of Image-Based Installation [ 1 ] and an idea of separating the operating system image from service software, this system solves the tedious problems involved when the large-scale cluster is divided into a number of functional pools; using the network transmit model of RM, this system reduces the cost of network bandwidth and significantly improves the efficiency in deployment; combining WOL [ 2 ] and PXE [ 3 ], the system provides the function of single control point and lightens the workload of the system administrator. So this system can solve the problems of current cluster deployment mechanisms, such as inefficiency, imperfection of automated node configuration, and only supporting the Linux-based operating system deployment, etc.

The deployment system consists of the deployment server, image servers, and target nodes. The deployment server is the core of the entire deployment system, which provides DHCP and TFTP service to ensure that the deployment control program can finish the deployment of target nodes after the cluster nodes start up from the NIC. Image servers mainly store the images and applications which can be accessed by the deployment server or target nodes by the NFS service. Target nodes are the nodes which need to be deployed in the cluster.

Before the deployment process, the image of the source node and the service environment of the deployment server and image server should be prepared. During the deployment, the target node communicates with the deployment server by using PXE and WOL, and then the deployment server deploys the corresponding image and application service to the target nodes through the RM method. Finally, the target nodes finish their configurations.

In the same experimental environment, some experiments respectively for this system, clonesys, and a deployment system identified by X have been built. As proved in experiments, this system can build a cluster more quickly and efficiently.
Constructing a Large Scale Wireless Sensors Network and Resources Scheduling among Multiple Personal Area Networks
Authors: Cheng Xiaoliang , Deng Zhidong
Published: January 2009

Constructing a Large Scale Wireless Sensors NetworkA real challenge of wireless sensors network applications is how to expand it to a larger scale. We proposed the idea of “One Zone Multi-PAN (Personal Area Network)” to build a Large-Scale Wireless Sensors Network (LS-WSN). Its key points include: the elementary component of LS-WSN is PAN; different PANs work on different channels; different PANs use customized policies and execute different tasks; every PAN covers and surveillances the same area, but senses different circumstance information.

Based on the idea, we proposed a two-level distributed LS-WSN model. The first level is the PAN-level, which works in a distributed mode. On this level, the up to 16 PANs bridged by a specially designed gateway coexist like a multi-layer sandwich. This gateway is a common children node of different PANs; therefore it can join in different PANs in a time-sharing mode. The second level is the inner-PAN-level, whose work mode is determined by the specific manufacturer.

The size of this model can be expanded up to 16 times of the size of a single PAN. Furthermore, QoS of LS-WSN can be guaranteed, data fusion and data management can be simplified and improved. Using Zigbee stack, we set up a prototype system of LS-WSN, whose performances are validated by our experiments. Resources Scheduling among PANsFor executing resource reconfiguration in LS-WSN, we proposed an application framework of resources scheduling (RSAF). Its key principles include: radio channels, superframe time-slots, and energy resources are named as “Common Resources;” “the whole network is more important than a single PAN” in LS-WSN; keep the key PANs alive; the lifespan of a LS-WSN is determined by that of key PANs.

RSAF can be comprehended as a collaboration mechanism at PAN level. It includes three components: superframe time-slots scheduling, radio channel scheduling, and energy scheduling. Their algorithms are different. Especially, a typical working cycle of energy scheduling contains four steps. First, the coordinators of different PANs gather different PANs' state information in a piggyback mode. Then the gateway periodically evaluates different PANs' states and makes the decisions of resources scheduling. After that, the specified coordinators send the control messages to certain nodes. Finally, the specified nodes will join and reinforce the key PAN in danger due to certain reasons (e.g., out of energy). Our experimental results validate the feasibility of RSAF in our prototype system.
A Hybrid Collision Resolution Protocol for Passive RFID Tag Identification
Authors: Xin-Qing Yan , Zhou-Ping Yin , You-Lun Xiong
Published: January 2009

Wireless communication channel collision of RFID system is a key issue that affects the pervasive application of the system, especially for passive RFID system due to the constrained communication ability and energy supply of tags. The collision resolution protocols suggested can be categorized into deterministic tree based protocols and probabilistic frame slot ALOHA based protocols. A hybrid protocol, which combines the query tree protocol and dynamic framed slotted ALOHA protocol, is presented here. In this protocol, at the beginning of each identification frame, the reader broadcasts a query command message which contains a suffix string and integer to indicate a frame size used in this frame to all tags in its vicinity, and every tag whose data match the specified suffix string randomly selects a slot in the frame to transmit its data to the reader. After each round, based on the different occupying situation of slots, the reader re-estimates the number of tags in its range, and according to the identification accuracy required, decides whether to split the group of tags to be identified into sub-groups or not, and adjust the suffix string and select a suitable frame size for the command messages of the following frames. Through this repeated identification and division process, the RFID tags can be identified within a number of frames.

Some key factors that influence the efficiency of the identification are also discussed based on binomial distribution model. Three methods for the tag population estimation are examined and their accuracies are compared, and the optimum frame size for the identification of different number of tags is given in consideration of the throughput and efficiency.

To verify the performance of the hybrid protocol, a numeric simulation is performed, in which 100 groups of SGTIN-96 encoded tags are generated randomly. Simulation shows that this hybrid protocol outperforms other frame slot ALOHA based collision resolution protocols, especially when there are a large number of RFID tags to be identified. The overall throughput of the hybrid protocol is kept around 34.8% when there are more than 40 tags, near the theoretical maximum value 36.8%. A linear relationship between the number of tags and the total frames and slots required is also observed in the numeric simulation.
READ: Reliability-Guaranteed Data Forwarding Protocol of Correlated Data in Wireless Sensor Networks
Authors: Zhang Zengjun , Luo Hong
Published: January 2009

Advances in microelectronic mechanical systems (MEMS) and wireless communication technologies have enabled wireless sensor networks (WSNs) to do a wide range of tasks, such as environmental detection, traffic monitoring, and control. WSNs are composed of hundreds or even thousands of sensor nodes. They are designed and implemented for monitoring the physical world, gathering sensed information, and transmitting the generated data packets to interested end users. In emergent event reporting applications, such as forest fire detection and toxic gas leak detection, sensor nodes detect events or phenomena respectively and report sensed data to sink node as soon as possible.

WSNs are aiming at gathering integrated information rather than collecting individual data packets. Although each sensor node may seem to be lacking in capability and reliability, a collective effort of the sensor nodes may provide sensing capabilities that satisfy the end users' needs. Since generated data packets at nodes are not independent, data correlation should be taken into consideration. Instead of reporting the raw data at 100% probability, sensor nodes in READ utilize their processing abilities to carry out simple computations locally and report it at the minimal probability. It uses combined methods of multi-point coverage and multi-path forwarding but not doing in-network data aggregation. READ uses ReInforM for multi-path data packets forwarding and controls the number of copies by exploiting the data correlation among neighbor nodes with Data Correlation Processing (DCP) algorithm. To suppress data transmission, READ subtracts redundancy from data packets only using local knowledge of neighbor information and topology. Such suppression of data packets transmissions enables information gathering with the lowest traffic without compromising on the integrated information.

Our simulation witnessed the fact that READ ensured the integrated information in event area was gathered and transferred to sink node at a desired level of reliability. The total data transmissions were tremendously cut down and the power consumption was dramatically economized compared with protocols not using DCP (N-DCP).
Packet-Level FEC Research over Wireless Networks
Authors: Liu Lin , Zhang Yunyi , Dong Xiaoshe
Published: January 2009

Over wireless networks, interference caused by external sources, multipath fading due to terrestrial obstruction, and the mobility of transmitters or receivers will result in bursty errors of transmitted packets. To deal with the problem, a packet-level XOR-FEC (forward error control), which improves an FEC scheme what Nachum Shacham and Paul McKenney proposed in an IEEE conference paper in 1990 named Packet recovery in high-speed networks using coding and buffer management, is proposed. The improved scheme, under certain conditions, can recover packets of both corruption and erasure. Because its main operation only involves the use of exclusive-or (XOR), it is low complexity. The scheme has been simulated and can be implemented with software. Simulation experiment results show that the improved scheme could decrease the number of redundant packets, so that the amount of computing to encode and decode can be saved and under certain conditions the XOR-FEC scheme could decrease the PER (packet error rate) without increasing the redundant rate.

From the scheme that Nachum Shacham and Paul McKenney proposed, it can be seen that: The scheme does not provide a method to check errors in a packet, so only lost packets can be recovered but corrupted packets can not be corrected Using both row and column parity packets increases the number of redundant packets While receivers gain packets and correct errors in every batch of packets, there is much delay among batches

To improve the scheme of Nachum Shacham and Paul McKenney: Using checksum field in every packet to distinguish damaged packets Only add to each column of the array of data packets a parity packet To recover packets in multimedia data transport, a double-window scheme is proposed to decrease the delay among batches of packets and to smooth the jitter among packets in receivers. Experiments show that by adjusting sending windows, under almost the same PER and redundant rate, improved scheme could recover more packets than a packet-level software FEC scheme based on the Reed-Solomon code. Besides, in an experiment, using the improved XOR-FEC, the packet error rate was reduced from about 5.7% to 0.7% and only around 33.3% of redundant packets were injected
Nosocomial Outbreak of Infection With Pan–Drug-ResistantAcinetobacter baumanniiin a Tertiary Care University Hospital
Authors: Valencia Raquel , Arroyo Luis A. , Conde Manuel , Aldana Josefa M. , Torres María-José , Fernández-Cuenca Felipe , Garnacho-Montero José , Cisneros José M. , Ortiz Carlos , Pachón Jerónimo , Aznar Javier
Published: January 2009

Objective.

TO describe what is, to our knowledge, the first nosocomial outbreak of infection with pan–drug-resistant (including colistin-resistant)Acinetobacter baumannii,to determine the risk factors associated with these types of infections, and to determine their clinical impact.

Design.

Nested case-control cohort study and a clinical-microbiological study.

Setting.

A 1,521-bed tertiary care university hospital in Seville, Spain.

Patients.

Case patients were inpatients who had a pan-drug-resistantA. baumanniiisolate recovered from a clinical or surveillance sample obtained at least 48 hours after admission to an intensive care unit (ICU) during the time of the epidemic outbreak. Control patients were patients who were admitted to any of the “boxes” (ie, rooms that partition off a distinct area for a patient's bed and the equipment needed to care for the patient) of an ICU for at least 48 hours during the time of the epidemic outbreak.

Results.

All the clinical isolates had similar antibiotic susceptibility patterns (ie, they were resistant to all the antibiotics tested, including Colistin), and, on the basis of repetitive extragenic palindromic-polymerase chain reaction, it was determined that all of them were of the same clone. The previous use of quinolones and glycopeptides and an ICU stay were associated with the acquisition of infection or colonization with pan-drug-resistant A.baumannii.To control this outbreak, we implemented the following multicomponent intervention program: the performance of environmental decontamination of the ICUs involved, an environmental survey, a revision of cleaning protocols, active surveillance for colonization with pan-drug-resistantA. baumannii,educational programs for the staff, and the display of posters that illustrate contact isolation measures and antimicrobial use recommendations.

Conclusions.

We were not able to identify the common source for these cases of infection, but the adopted measures have proven to be effective at controlling the outbreak.
Cooperative Assembly and Misfolding of CFTR Domains In Vivo
Authors: Du Kai , Lukacs Gergely L.
Published: January 2009

The cystic fibrosis transmembrane conductance regulator (CFTR) architecture consists of two membrane spanning domains (MSD1 and -2), two nucleotide binding domains (NBD1 and -2), and a regulatory (R) domain. Several point mutations lead to the channel misprocessing, with limited structural perturbation of the mutant domain. To gain more insight into the basis of CFTR folding defect, the contribution of domain-wise and cooperative domain folding was assessed by determining 1) the minimal domain combination that is recognized as native and can efficiently escape the endoplasmic reticulum (ER) retention and 2) the impact of mutation on the conformational coupling among domains. One-, two-, three-, and most of the four-domain assemblies were retained at the ER. Solubilization mutations, however, rescued the NBD1 processing defect conceivably by thermodynamic stabilization. The smallest folding unit that traversed the secretory pathway was composed of MSD1-NBD1-R-MSD2 as a linear or split polypeptide. Cystic fibrosis-causing missense mutations in the MSD1, NBD1, MSD2, and NBD2 caused conformational defect in multiple domains. We propose that cooperative posttranslational folding is required for domain stabilization and provides a plausible explanation for the global misfolding caused by point mutations dispersed along the full-length CFTR.
Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration
Authors: Severson Eric A. , Lee Winston Y. , Capaldo Christopher T. , Nusrat Asma , Parkos Charles A.
Published: January 2009

Junctional adhesion molecule-A (JAM-A) is a transmembrane tight junction protein that has been shown to regulate barrier function and cell migration through incompletely understood mechanisms. We have previously demonstrated that JAM-A regulates cell migration by dimerization of the membrane-distal immunoglobulin-like loop and a C-terminal postsynaptic density 95/disc-large/zona occludens (PDZ) binding motif. Disruption of dimerization resulted in decreased epithelial cell migration secondary to diminished levels of β1 integrin and active Rap1. Here, we report that JAM-A is physically and functionally associated with the PDZ domain-containing molecules Afadin and PDZ-guanine nucleotide exchange factor (GEF) 2, but not zonula occludens (ZO)-1, in epithelial cells, and these interactions mediate outside-in signaling events. Both Afadin and PDZ-GEF2 colocalized and coimmunoprecipitated with JAM-A. Furthermore, association of PDZ-GEF2 with Afadin was dependent on the expression of JAM-A. Loss of JAM-A, Afadin, or PDZ-GEF2, but not ZO-1 or PDZ-GEF1, similarly decreased cellular levels of activated Rap1, β1 integrin protein, and epithelial cell migration. The functional effects observed were secondary to decreased levels of Rap1A because knockdown of Rap1A, but not Rap1B, resulted in decreased β1 integrin levels and reduced cell migration. These findings suggest that JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates β1 integrin levels and cell migration.
Serial dilution curve: a new method for analysis of reverse phase protein array data
Authors: Zhang Li , Wei Qingyi , Mao Li , Liu Wenbin , Mills Gordon B. , Coombes Kevin
Published: January 2009

Reverse phase protein arrays (RPPAs) are a powerful high-throughput tool for measuring protein concentrations in a large number of samples. In RPPA technology, the original samples are often diluted successively multiple times, forming dilution series to extend the dynamic range of the measurements and to increase confidence in quantitation. An RPPA experiment is equivalent to running multiple ELISA assays concurrently except that there is usually no known protein concentration from which one can construct a standard response curve. Here, we describe a new method called ‘serial dilution curve for RPPA data analysis’. Compared with the existing methods, the new method has the advantage of using fewer parameters and offering a simple way of visualizing the raw data. We showed how the method can be used to examine data quality and to obtain robust quantification of protein concentrations.

Availability: A computer program in R for using serial dilution curve for RPPA data analysis is freely available at http://odin.mdacc.tmc.edu/~zhangli/RPPA.

Contact:  lzhangli@mdanderson.org
A novel meta-analysis method exploiting consistency of high-throughput experiments
Authors: Rajaram Satwik
Published: January 2009

Motivation: Large-scale biological experiments provide snapshots into the huge number of processes running in parallel within the organism. These processes depend on a large number of (hidden) (epi)genetic, social, environmental and other factors that are out of experimentalists' control. This makes it extremely difficult to identify the dominant processes and the elements involved in them based on a single experiment. It is therefore desirable to use multiple sets of experiments targeting the same phenomena while differing in some experimental parameters (hidden or controllable). Although such datasets are becoming increasingly common, their analysis is complicated by the fact that the various biological elements could be influenced by different sets of factors.

Results: The central hypothesis of this article is that biologically related elements and processes are affected by changes in similar ways while unrelated ones are affected differently. Thus, the relations between related elements are more consistent across experiments. The method outlined here looks for groups of elements with robust intra-group relationships in the expectation that they are related. The major groups of elements may be identified in this way. The strengths of relationships per se are not valued, just their consistency. This represents a completely novel and unutilized source of information. In the analysis of time course microarray experiments, I found cell cycle- and ribosome-related genes to be the major groups. Despite not looking for these groups in particular, the identification of these genes rivals that of methods designed specifically for this purpose.

Availability: A C++ implementation is available at http://www.rinst.org/ICS/ICS_Programs.tar.gz.

Contact:  srajaram@uiuc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fragment-based identification of druggable ‘hot spots’ of proteins using Fourier domain correlation techniques
Authors: Brenke Ryan , Kozakov Dima , Chuang Gwo-Yu , Beglov Dmitri , Hall David , Landon Melissa R. , Mattos Carla , Vajda Sandor
Published: January 2009

Motivation: The binding sites of proteins generally contain smaller regions that provide major contributions to the binding free energy and hence are the prime targets in drug design. Screening libraries of fragment-sized compounds by NMR or X-ray crystallography demonstrates that such ‘hot spot’ regions bind a large variety of small organic molecules, and that a relatively high ‘hit rate’ is predictive of target sites that are likely to bind drug-like ligands with high affinity. Our goal is to determine the ‘hot spots’ computationally rather than experimentally.

Results: We have developed the FTMAP algorithm that performs global search of the entire protein surface for regions that bind a number of small organic probe molecules. The search is based on the extremely efficient fast Fourier transform (FFT) correlation approach which can sample billions of probe positions on dense translational and rotational grids, but can use only sums of correlation functions for scoring and hence is generally restricted to very simple energy expressions. The novelty of FTMAP is that we were able to incorporate and represent on grids a detailed energy expression, resulting in a very accurate identification of low-energy probe clusters. Overlapping clusters of different probes are defined as consensus sites (CSs). We show that the largest CS is generally located at the most important subsite of the protein binding site, and the nearby smaller CSs identify other important subsites. Mapping results are presented for elastase whose structure has been solved in aqueous solutions of eight organic solvents, and we show that FTMAP provides very similar information. The second application is to renin, a long-standing pharmaceutical target for the treatment of hypertension, and we show that the major CSs trace out the shape of the first approved renin inhibitor, aliskiren.

Availability: FTMAP is available as a server at http://ftmap.bu.edu/.

Contact:  vajda@bu.edu

Supplementary information:  Supplementary Material is available at Bioinformatics online.
Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)
Authors: Hawkins Nathaniel M. , Huang Zhen , Pieper Karen S. , Solomon Scott D. , Kober Lars , Velazquez Eric J. , Swedberg Karl , Pfeffer Marc A. , McMurray John J.V. , Maggioni Aldo P. ,   for the Valsartan in Acute Myocardial Infarction Trial Investigators
Published: January 2009

Aims

Chronic obstructive pulmonary disease is an independent predictor of mortality in patients with myocardial infarction (MI). However, the impact on mode of death and risk of atherosclerotic events is unknown.

Methods and results

We assessed the risk of death and major cardiovascular (CV) events associated with chronic obstructive pulmonary disease in 14 703 patients with acute MI enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) trial. Cox proportional hazards models were used to evaluate the relationship between chronic obstructive pulmonary disease and CV outcomes. A total of 1258 (8.6%) patients had chronic obstructive pulmonary disease. Over a median follow‐up period of 24.7 months, all‐cause mortality was 30% in patients with chronic obstructive pulmonary disease, compared with 19% in those without. The adjusted hazard ratio (HR) for mortality was 1.14 (95% confidence interval 1.02–1.28). This reflected increased incidence of both non‐CV death [HR 1.86 (1.43–2.42)] and sudden death [HR 1.26 (1.03–1.53)]. The unadjusted risk of all pre‐specified CV outcomes was increased. However, after multivariate adjustment, chronic obstructive pulmonary disease was not an independent predictor of atherosclerotic events [MI or stroke: HR 0.98 (0.77–1.23)]. Mortality was significantly lower in patients receiving beta‐blockers, irrespective of airway disease.

Conclusion

In high‐risk patients with acute MI, chronic obstructive pulmonary disease is associated with increased mortality and non‐fatal clinical events (both CV and non‐CV). However, patients with chronic obstructive pulmonary disease did not experience a higher rate of atherosclerotic events.
Clonidine and Dexmedetomidine Produce Antinociceptive Synergy in Mouse Spinal Cord
Authors: Fairbanks Carolyn A. , Kitto Kelley F. , Nguyen H Oanh , Stone Laura S. , Wilcox George L.
Published: January 2009

Background

Synergy between drugs manifests with increased potency and/or efficacy of the combination relative to either agonist given alone. Synergy is typically observed between drugs of different classes, as is the case with the alpha-adrenergic-opioid receptor synergy often observed in preclinical studies. However, rare studies report synergy between agonists of the same class. The current study examined the analgesic interaction between two intrathecally injected alpha2-adrenergic receptor (AR) agonists previously thought to act at the same receptor subtype when given spinally.

Methods

Mice were given clonidine, dexmedetomidine, or the combination spinally to evaluate the interaction between these two agonists. The ED50 values were calculated, and the interactions were tested by isobolographic analysis. The rotarod test was performed in the same mice after the completion of analgesic assessment to assess motor or sedative effects. These experiments were performed in outbred mice as well as in mice with mutant alpha2A ARs, alpha2C AR knockout mice, or wild-type controls. Finally, analgesic cross-tolerance between clonidine and dexmedetomidine was evaluated.

Results

Clonidine and dexmedetomidine interacted synergistically in all lines except the alpha2C AR knockout line, implicating alpha2C ARs in the interaction. In addition, clonidine and dexmedetomidine did not show analgesic cross-tolerance in the outbred strain, suggesting that the two drugs have distinct mechanisms of action.

Conclusions

The current study introduces a new synergistic agonist pair, clonidine-dexmedetomidine. These two drugs seem to require the alpha2A AR for spinal analgesia when given separately; when delivered as a combination, the resultant synergistic interaction requires the alpha2C AR as well.
Changing the Paradigm: Omegaven for the Treatment of Liver Failure in Pediatric Short Bowel Syndrome
Authors: Diamond Ivan R , Sterescu Anca , Pencharz Paul B , Kim Jae H , Wales Paul W
Published: January 2009

Background:

Parenteral omega‐3 fatty acids, such as Omegaven, may benefit patients with pediatric short bowel syndrome (SBS) who develop parenteral nutrition–associated liver disease (PNALD).

Patients and Methods:

Retrospective cohort describing the outcome of all 12 children with SBS and advanced PNALD who were treated with Omegaven (target omega‐6 to omega‐3 fatty acid ratio = 1:1 to 2:1).

Results:

The median age was 7.5 (range 3.6–46) months, and median parenteral nutrition duration before starting Omegaven was 28.4 (range 15.3–55.3) weeks. Median initial serum conjugated bilirubin was 137 (range 54–203) μmol/L (8.06 [3.18–11.94] mg/dL). Of the 12 patients, 9 had complete and sustained resolution of hyperbilirubinemia within a median of 24 (range 7–37) weeks, and all are no longer being considered for liver transplantation. Improvements in markers of hepatic inflammation as well as nutritional status also were noted in these patients. Three patients received a liver‐intestine transplant while taking Omegaven. There were no complications attributable to Omegaven.

Conclusions:

Omegaven is associated with restoration of liver function in patients with SBS and advanced liver disease. Parenteral omega‐3 fatty acids, such as Omegaven, have the potential to fundamentally alter the paradigm of neonatal SBS from one of early death or transplantation from liver failure to a more chronic disease. More children with SBS should achieve full enteral tolerance and those who do not have the capacity for intestinal adaptation should be able to survive and receive an intestinal graft when older.
Trichoderma virens, a Plant Beneficial Fungus, Enhances Biomass Production and Promotes Lateral Root Growth through an Auxin-Dependent Mechanism in Arabidopsis
Authors: Contreras-Cornejo Hexon Angel , Macías-Rodríguez Lourdes , Cortés-Penagos Carlos , López-Bucio José
Published: January 2009

Trichoderma species belong to a class of free-living fungi beneficial to plants that are common in the rhizosphere. We investigated the role of auxin in regulating the growth and development of Arabidopsis (Arabidopsis thaliana) seedlings in response to inoculation with Trichoderma virens and Trichoderma atroviride by developing a plant-fungus interaction system. Wild-type Arabidopsis seedlings inoculated with either T. virens or T. atroviride showed characteristic auxin-related phenotypes, including increased biomass production and stimulated lateral root development. Mutations in genes involved in auxin transport or signaling, AUX1, BIG, EIR1, and AXR1, were found to reduce the growth-promoting and root developmental effects of T. virens inoculation. When grown under axenic conditions, T. virens produced the auxin-related compounds indole-3-acetic acid, indole-3-acetaldehyde, and indole-3-ethanol. A comparative analysis of all three indolic compounds provided detailed information about the structure-activity relationship based on their efficacy at modulating root system architecture, activation of auxin-regulated gene expression, and rescue of the root hair-defective phenotype of the rhd6 auxin response Arabidopsis mutant. Our results highlight the important role of auxin signaling for plant growth promotion by T. virens.
Evidence for interspecific hybridization between native white‐spotted charr Salvelinus leucomaenis and non‐native brown trout Salmo trutta on Hokkaido Island, Japan
Authors: Kitano S. , Hasegawa K. , Maekawa K.
Published: January 2009

Hybrids between native white‐spotted charr Salvelinus leucomaenis and non‐native brown trout Salmo trutta were identified in streams of Hokkaido, Japan, using both appearance and genetic characters. The DNA analyses indicated that the specimens were hybrids between female S. leucomaenis and male S. trutta. Occurrence of such hybrids implies increased mating opportunities between these species in wild streams.
Development, validation and dissemination of instructional materials: an analysis
Authors: CREECH JANE C. , ARSHAM G. M.
Published: January 2009

This paper describes the activities of SIMO (Self‐Instructional Materials in Ophthalmology), a 2‐year project to develop four slide/tape units and one videocassette in basic ophthalmology for medical students,† The background of the project, some observations regarding pitfalls in the developmental process, data on product evaluation, and factors in effective dissemination are presented. Instructional effectiveness was documented using measures of knowledge, skill in recognizing abnormalities, and performance of diagnostic and management techniques.
Performance of women medical graduates from Medical College, Baroda, 1949–14
Authors: BHATT R. V. , SONI J. M. , PATEL N. F.
Published: January 2009

Women account for 15% of the total admissions in medicine. 271 women have graduated from Medical College, Baroda in 25 years. The examination results are better in women than in men. Obstetrics and gynaecology is the most common speciality selected by women. Job satisfaction is found in 87% of women. Unmarried women account for 15%, 66% have married a doctor and 19% are married to non‐ medical spouse. Emigration is to the extent of 39%.
Mycoplasma pneumoniae J‐domain protein required for terminal organelle function
Authors: Cloward Jason M. , Krause Duncan C.
Published: January 2009

The cell wall‐less prokaryote Mycoplasma pneumoniae causes tracheobronchitis and primary atypical pneumonia in humans. Colonization of the respiratory epithelium requires proper assembly of a complex, multifunctional, polar terminal organelle. Loss of a predicted J‐domain protein also having domains unique to mycoplasma terminal organelle proteins (TopJ) resulted in a non‐motile, adherence‐deficient phenotype. J‐domain proteins typically stimulate ATPase activity of Hsp70 chaperones to bind nascent peptides for proper folding, translocation or macromolecular assembly, or to resolve stress‐induced protein aggregates. By Western immunoblotting all defined terminal organelle proteins examined except protein P24 remained at wild‐type levels in the topJ mutant; previous studies established that P24 is required for normal initiation of terminal organelle formation. Nevertheless, terminal organelle proteins P1, P30, HMW1 and P41 failed to localize to a cell pole, and when evaluated quantitatively, P30 and HMW1 foci were undetectable in >40% of cells. Complementation of the topJ mutant with the recombinant wild‐type topJ allele largely restored terminal organelle development, gliding motility and cytadherence. We propose that this J‐domain protein, which localizes to the base of the terminal organelle in wild‐type M. pneumoniae, functions in the late stages of assembly, positioning, or both, of nascent terminal organelles.
Socio‐environmental predictors of Barmah forest virus transmission in coastal areas, Queensland, Australia
Authors: Naish Suchithra , Hu Wenbiao , Nicholls Neville , Mackenzie John S. , Dale Pat , McMichael Anthony J. , Tong Shilu
Published: January 2009

Objective  To assess the socio‐environmental predictors of Barmah forest virus (BFV) transmission in coastal areas, Queensland, Australia.

Methods  Data on BFV notified cases, climate, tidal levels and socioeconomic index for area (SEIFA) in six coastal cities, Queensland, for the period 1992–2001 were obtained from the relevant government agencies. Negative binomial regression models were used to assess the socio‐environmental predictors of BFV transmission.

Results  The results show that maximum and minimum temperature, rainfall, relative humidity, high and low tide were statistically significantly associated with BFV incidence at lags 0–2 months. The fitted negative binomial regression models indicate a significant independent association of each of maximum temperature (β = 0.139, P = 0.000), high tide (β = 0.005, P = 0.000) and SEIFA index (β = −0.010, P = 0.000) with BFV transmission after adjustment for confounding variables.

Conclusions  The transmission of BFV disease in Queensland coastal areas seemed to be determined by a combination of local social and environmental factors. The model developed in this study may have applications in the control and prevention of BFV disease in these areas.