Median network analysis of defectively sequenced entire mitochondrial genomes from early and contemporary disease studies

Sequence analysis of the mitochondrial genome has become a routine method in the study of mitochondrial diseases. Quite often, the sequencing efforts in the search of pathogenic or disease-associated mutations are affected by technical and interpretive pr

Tracing the Origins of Hakka and Chaoshanese by Mitochondrial DNA Analysis

Hakka and Chaoshanese are two unique Han populations residing in southern China but with northern Han (NH) cultural traditions and linguistic influences. Although most of historical records indicate that both populations migrated from northern China in the last two thousand years, no consensus on their origins has been reached so far. To shed more light on the origins of Hakka and Chaoshanese, mitochondrial DNAs (mtDNAs) of 170 Hakka from Meizhou and 102 Chaoshanese from Chaoshan area, Guangdong Province, were analyzed. Our results show that some southern Chinese predominant haplogroups, e.g. B, F, and M7, have relatively high frequencies in both populations. Although median network analyses show that Hakka/Chaoshanese share some haplotypes with NH, interpopulation comparison reveals that both populations show closer affinity with southern Han (SH) populations than with NH. In consideration of previous results from nuclear gene (including Y chromosome) research, it is likely that matrilineal landscapes of both Hakka and Chaoshanese have largely been shaped by the local people during their migration southward and/or later colonization in southern China, and factors such as cultural assimilation, patrilocality, and even sex-bias in the immigrants might have played important roles during the process. Am J Phys Anthropol 141:124-130, 2010. (C) 2009 Wiley-Liss, Inc.

Network density and the p-median solution

The p-medianmodel is commonly used to find optimal locations of facilities for geographically distributed demands. So far, there are few studies that have considered the importance of the road network in the model. However, Han, Håkansson, and Rebreyend (2013) examined the solutions of the p-median model with densities of the road network varying from 500 to 70,000 nodes. They found as the density went beyond some 10,000 nodes, solutions have no further improvements but gradually worsen. The aim of this study is to check their findings by using an alternative heuristic being vertex substitution, as a complement to their using simulated annealing. We reject the findings in Han et al (2013). The solutions do not further improve as the nodes exceed 10,000, but neither do the solutions deteriorate.

Upgrading arc median shortest path problem for an urban transportation network

In this paper, we propose an algorithm for an upgrading arc median shortest path problem for a transportation network. The problem is to identify a set of nondominated paths that minimizes both upgrading cost and overall travel time of the entire network. These two objectives are realistic for transportation network problems, but of a conflicting and noncompensatory nature. In addition, unlike upgrading cost which is the sum of the arc costs on the path, overall travel time of the entire network cannot be expressed as a sum of arc travel times on the path. The proposed solution approach to the problem is based on heuristic labeling and exhaustive search techniques, in criteria space and solution space, respectively. The first approach labels each node in terms of upgrading cost, and deletes cyclic and infeasible paths in criteria space. The latter calculates the overall travel time of the entire network for each feasible path, deletes dominated paths on the basis of the objective vector and identifies a set of Pareto optimal paths in the solution space. The computational study, using two small-scale transportation networks, has demonstrated that the algorithm proposed herein is able to efficiently identify a set of nondominated median shortest paths, based on two conflicting and noncompensatory objectives.

Filter design using radial basis function neural network and genetic algorithm for improved operational health monitoring

The problem of denoising damage indicator signals for improved operational health monitoring of systems is addressed by applying soft computing methods to design filters. Since measured data in operational settings is contaminated with noise and outliers, pattern recognition algorithms for fault detection and isolation can give false alarms. A direct approach to improving the fault detection and isolation is to remove noise and outliers from time series of measured data or damage indicators before performing fault detection and isolation. Many popular signal-processing approaches do not work well with damage indicator signals, which can contain sudden changes due to abrupt faults and non-Gaussian outliers. Signal-processing algorithms based on radial basis function (RBF) neural network and weighted recursive median (WRM) filters are explored for denoising simulated time series. The RBF neural network filter is developed using a K-means clustering algorithm and is much less computationally expensive to develop than feedforward neural networks trained using backpropagation. The nonlinear multimodal integer-programming problem of selecting optimal integer weights of the WRM filter is solved using genetic algorithm. Numerical results are obtained for helicopter rotor structural damage indicators based on simulated frequencies. Test signals consider low order polynomial growth of damage indicators with time to simulate gradual or incipient faults and step changes in the signal to simulate abrupt faults. Noise and outliers are added to the test signals. The WRM and RBF filters result in a noise reduction of 54 - 71 and 59 - 73% for the test signals considered in this study, respectively. Their performance is much better than the moving average FIR filter, which causes significant feature distortion and has poor outlier removal capabilities and shows the potential of soft computing methods for specific signal-processing applications.

Filter design using radial basis function neural network and genetic algorithm for improved operational health monitoring

The problem of denoising damage indicator signals for improved operational health monitoring of systems is addressed by applying soft computing methods to design filters. Since measured data in operational settings is contaminated with noise and outliers, pattern recognition algorithms for fault detection and isolation can give false alarms. A direct approach to improving the fault detection and isolation is to remove noise and outliers from time series of measured data or damage indicators before performing fault detection and isolation. Many popular signal-processing approaches do not work well with damage indicator signals, which can contain sudden changes due to abrupt faults and non-Gaussian outliers. Signal-processing algorithms based on radial basis function (RBF) neural network and weighted recursive median (WRM) filters are explored for denoising simulated time series. The RBF neural network filter is developed using a K-means clustering algorithm and is much less computationally expensive to develop than feedforward neural networks trained using backpropagation. The nonlinear multimodal integer-programming problem of selecting optimal integer weights of the WRM filter is solved using genetic algorithm. Numerical results are obtained for helicopter rotor structural damage indicators based on simulated frequencies. Test signals consider low order polynomial growth of damage indicators with time to simulate gradual or incipient faults and step changes in the signal to simulate abrupt faults. Noise and outliers are added to the test signals. The WRM and RBF filters result in a noise reduction of 54 - 71 and 59 - 73% for the test signals considered in this study, respectively. Their performance is much better than the moving average FIR filter, which causes significant feature distortion and has poor outlier removal capabilities and shows the potential of soft computing methods for specific signal-processing applications. (C) 2005 Elsevier B. V. All rights reserved.

CTFS-ForestGEO: a worldwide network monitoring forests in an era of global change

Global change is impacting forests worldwide, threatening biodiversity and ecosystem services including climate regulation. Understanding how forests respond is critical to forest conservation and climate protection. This review describes an international network of 59 long-term forest dynamics research sites (CTFS-ForestGEO) useful for characterizing forest responses to global change. Within very large plots (median size 25ha), all stems 1cm diameter are identified to species, mapped, and regularly recensused according to standardized protocols. CTFS-ForestGEO spans 25 degrees S-61 degrees N latitude, is generally representative of the range of bioclimatic, edaphic, and topographic conditions experienced by forests worldwide, and is the only forest monitoring network that applies a standardized protocol to each of the world's major forest biomes. Supplementary standardized measurements at subsets of the sites provide additional information on plants, animals, and ecosystem and environmental variables. CTFS-ForestGEO sites are experiencing multifaceted anthropogenic global change pressures including warming (average 0.61 degrees C), changes in precipitation (up to +/- 30% change), atmospheric deposition of nitrogen and sulfur compounds (up to 3.8g Nm(-2)yr(-1) and 3.1g Sm(-2)yr(-1)), and forest fragmentation in the surrounding landscape (up to 88% reduced tree cover within 5km). The broad suite of measurements made at CTFS-ForestGEO sites makes it possible to investigate the complex ways in which global change is impacting forest dynamics. Ongoing research across the CTFS-ForestGEO network is yielding insights into how and why the forests are changing, and continued monitoring will provide vital contributions to understanding worldwide forest diversity and dynamics in an era of global change.

Overlay Network Creation and Maintenance with Selfish Users

Overlay networks have been used for adding and enhancing functionality to the end-users without requiring modifications in the Internet core mechanisms. Overlay networks have been used for a variety of popular applications including routing, file sharing, content distribution, and server deployment. Previous work has focused on devising practical neighbor selection heuristics under the assumption that users conform to a specific wiring protocol. This is not a valid assumption in highly decentralized systems like overlay networks. Overlay users may act selfishly and deviate from the default wiring protocols by utilizing knowledge they have about the network when selecting neighbors to improve the performance they receive from the overlay. This thesis goes against the conventional thinking that overlay users conform to a specific protocol. The contributions of this thesis are threefold. It provides a systematic evaluation of the design space of selfish neighbor selection strategies in real overlays, evaluates the performance of overlay networks that consist of users that select their neighbors selfishly, and examines the implications of selfish neighbor and server selection to overlay protocol design and service provisioning respectively. This thesis develops a game-theoretic framework that provides a unified approach to modeling Selfish Neighbor Selection (SNS) wiring procedures on behalf of selfish users. The model is general, and takes into consideration costs reflecting network latency and user preference profiles, the inherent directionality in overlay maintenance protocols, and connectivity constraints imposed on the system designer. Within this framework the notion of user’s "best response" wiring strategy is formalized as a k-median problem on asymmetric distance and is used to obtain overlay structures in which no node can re-wire to improve the performance it receives from the overlay. Evaluation results presented in this thesis indicate that selfish users can reap substantial performance benefits when connecting to overlay networks composed of non-selfish users. In addition, in overlays that are dominated by selfish users, the resulting stable wirings are optimized to such great extent that even non-selfish newcomers can extract near-optimal performance through naïve wiring strategies. To capitalize on the performance advantages of optimal neighbor selection strategies and the emergent global wirings that result, this thesis presents EGOIST: an SNS-inspired overlay network creation and maintenance routing system. Through an extensive measurement study on the deployed prototype, results presented in this thesis show that EGOIST’s neighbor selection primitives outperform existing heuristics on a variety of performance metrics, including delay, available bandwidth, and node utilization. Moreover, these results demonstrate that EGOIST is competitive with an optimal but unscalable full-mesh approach, remains highly effective under significant churn, is robust to cheating, and incurs minimal overheads. This thesis also studies selfish neighbor selection strategies for swarming applications. The main focus is on n-way broadcast applications where each of n overlay user wants to push its own distinct file to all other destinations as well as download their respective data files. Results presented in this thesis demonstrate that the performance of our swarming protocol for n-way broadcast on top of overlays of selfish users is far superior than the performance on top of existing overlays. In the context of service provisioning, this thesis examines the use of distributed approaches that enable a provider to determine the number and location of servers for optimal delivery of content or services to its selfish end-users. To leverage recent advances in virtualization technologies, this thesis develops and evaluates a distributed protocol to migrate servers based on end-users demand and only on local topological knowledge. Results under a range of network topologies and workloads suggest that the performance of the distributed deployment is comparable to that of the optimal but unscalable centralized deployment.

Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

BACKGROUND: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. METHODS: The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. RESULTS: During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. CONCLUSIONS: We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database.

BACKGROUND: The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. METHODS: The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. RESULTS: We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. CONCLUSIONS: In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

Dose-response relationship in phase 1 clinical trials: a European Drug Development Network (EDDN) Collaboration Study

Introduction: Because a dose–response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study, we evaluated the relationship between dose and efficacy in a large cohort of phase I patients with solid tumors.

Experimental Design: We collected data on 1,182 consecutive patients treated in phase I trials in 14 European institutions in 2005–2007. Inclusion criteria were: (i) patients treated within completed single-agent studies in which a maximum-administered dose was defined and (ii) RECIST/survival data available.

Results: Seventy-two percent of patients were included in trials with MTA (N = 854) and 28% in trials with CTX (N = 328). The objective response (OR) rate was 3% and disease control at 6 months was 11%. OR for CTX was associated with higher doses (median 92% of MTD); this was not the case for MTA, where patients achieving OR received a median of 50% of MTD. For trials with MTA, patients treated at intermediate doses (40%–80%) had better survival compared with those receiving low or high doses (P = 0.038). On the contrary, there was a direct association between higher dose and better OS for CTX agents (P = 0.003).

Conclusion: Although these results support the development of novel CTX based on MTD, we found no direct relationship between higher doses and response with MTA in unselected patients. However, the longest OS was seen in patients treated with MTA at intermediate doses (40%–80% of MTD)

Median Sets and Median Number of a Graph

A profile is a finite sequence of vertices of a graph. The set of all vertices of the graph which minimises the sum of the distances to the vertices of the profile is the median of the profile. Any subset of the vertex set such that it is the median of some profile is called a median set. The number of median sets of a graph is defined to be the median number of the graph. In this paper, we identify the median sets of various classes of graphs such as Kp − e, Kp,q forP > 2, and wheel graph and so forth. The median numbers of these graphs and hypercubes are found out, and an upper bound for the median number of even cycles is established.We also express the median number of a product graph in terms of the median number of their factors.

Road network and GPS tracking with data processing and quality assessment

GPS technology has been embedded into portable, low-cost electronic devices nowadays to track the movements of mobile objects. This implication has greatly impacted the transportation field by creating a novel and rich source of traffic data on the road network. Although the promise offered by GPS devices to overcome problems like underreporting, respondent fatigue, inaccuracies and other human errors in data collection is significant; the technology is still relatively new that it raises many issues for potential users. These issues tend to revolve around the following areas: reliability, data processing and the related application. This thesis aims to study the GPS tracking form the methodological, technical and practical aspects. It first evaluates the reliability of GPS based traffic data based on data from an experiment containing three different traffic modes (car, bike and bus) traveling along the road network. It then outline the general procedure for processing GPS tracking data and discuss related issues that are uncovered by using real-world GPS tracking data of 316 cars. Thirdly, it investigates the influence of road network density in finding optimal location for enhancing travel efficiency and decreasing travel cost. The results show that the geographical positioning is reliable. Velocity is slightly underestimated, whereas altitude measurements are unreliable.Post processing techniques with auxiliary information is found necessary and important when solving the inaccuracy of GPS data. The densities of the road network influence the finding of optimal locations. The influence will stabilize at a certain level and do not deteriorate when the node density is higher.

Heuristic optimization of the p-median problem and population re-distribution

This thesis contributes to the heuristic optimization of the p-median problem and Swedish population redistribution.   The p-median model is the most representative model in the location analysis. When facilities are located to a population geographically distributed in Q demand points, the p-median model systematically considers all the demand points such that each demand point will have an effect on the decision of the location. However, a series of questions arise. How do we measure the distances? Does the number of facilities to be located have a strong impact on the result? What scale of the network is suitable? How good is our solution? We have scrutinized a lot of issues like those. The reason why we are interested in those questions is that there are a lot of uncertainties in the solutions. We cannot guarantee our solution is good enough for making decisions. The technique of heuristic optimization is formulated in the thesis.   Swedish population redistribution is examined by a spatio-temporal covariance model. A descriptive analysis is not always enough to describe the moving effects from the neighbouring population. A correlation or a covariance analysis is more explicit to show the tendencies. Similarly, the optimization technique of the parameter estimation is required and is executed in the frame of statistical modeling. 

How do different densities in a network affect the optimal location of service centers?

The p-median problem is often used to locate p service centers by minimizing their distances to a geographically distributed demand (n). The optimal locations are sensitive to geographical context such as road network and demand points especially when they are asymmetrically distributed in the plane. Most studies focus on evaluating performances of the p-median model when p and n vary. To our knowledge this is not a very well-studied problem when the road network is alternated especially when it is applied in a real world context. The aim in this study is to analyze how the optimal location solutions vary, using the p-median model, when the density in the road network is alternated. The investigation is conducted by the means of a case study in a region in Sweden with an asymmetrically distributed population (15,000 weighted demand points), Dalecarlia. To locate 5 to 50 service centers we use the national transport administrations official road network (NVDB). The road network consists of 1.5 million nodes. To find the optimal location we start with 500 candidate nodes in the network and increase the number of candidate nodes in steps up to 67,000. To find the optimal solution we use a simulated annealing algorithm with adaptive tuning of the temperature. The results show that there is a limited improvement in the optimal solutions when nodes in the road network increase and p is low. When p is high the improvements are larger. The results also show that choice of the best network depends on p. The larger p the larger density of the network is needed.