Modelling the evolution of drug resistance in the presence of antiviral drugs

Abstract Background The emergence of drug resistance in treated populations and the transmission of drug resistant strains to newly infected individuals are important public health concerns in the prevention and control of infectious diseases such as HIV and influenza. Mathematical modelling may help guide the design of treatment programs and also may help us better understand the potential benefits and limitations of prevention strategies. Methods To explore further the potential synergies between modelling of drug resistance in HIV and in pandemic influenza, the Public Health Agency of Canada and the Mathematics for Information Technology and Complex Systems brought together selected scientists and public health experts for a workshop in Ottawa in January 2007, to discuss the emergence and transmission of HIV antiviral drug resistance, to report on progress in the use of mathematical models to study the emergence and spread of drug resistant influenza viral strains, and to recommend future research priorities. Results General lectures and round-table discussions were organized around the issues on HIV drug resistance at the population level, HIV drug resistance in Western Canada, HIV drug resistance at the host level (with focus on optimal treatment strategies), and drug resistance for pandemic influenza planning. Conclusion Some of the issues related to drug resistance in HIV and pandemic influenza can possibly be addressed using existing mathematical models, with a special focus on linking the existing models to the data obtained through the Canadian HIV Strain and DR Surveillance Program. Preliminary statistical analysis of these data carried out at PHAC, together with the general model framework developed by Dr. Blower and her collaborators, should provide further insights into the mechanisms behind the observed trends and thus could help with the prediction and analysis of future trends in the aforementioned items. Remarkable similarity between dynamic, compartmental models for the evolution of wild and drug resistance strains of both HIV and pandemic influenza may provide sufficient common ground to create synergies between modellers working in these two areas. One of the key contributions of mathematical modeling to the control of infectious diseases is the quantification and design of optimal strategies, combining techniques of operations research with dynamic modeling would enhance the contribution of mathematical modeling to the prevention and control of infectious diseases.</p

Classifying Imbalanced Data Sets by a Novel RE-Sample and Cost-Sensitive Stacked Generalization Method

Learning with imbalanced data sets is considered as one of the key topics in machine learning community. Stacking ensemble is an efficient algorithm for normal balance data sets. However, stacking ensemble was seldom applied in imbalance data. In this paper, we proposed a novel RE-sample and Cost-Sensitive Stacked Generalization (RECSG) method based on 2-layer learning models. The first step is Level 0 model generalization including data preprocessing and base model training. The second step is Level 1 model generalization involving cost-sensitive classifier and logistic regression algorithm. In the learning phase, preprocessing techniques can be embedded in imbalance data learning methods. In the cost-sensitive algorithm, cost matrix is combined with both data characters and algorithms. In the RECSG method, ensemble algorithm is combined with imbalance data techniques. According to the experiment results obtained with 17 public imbalanced data sets, as indicated by various evaluation metrics (AUC, GeoMean, and AGeoMean), the proposed method showed the better classification performances than other ensemble and single algorithms. The proposed method is especially more efficient when the performance of base classifier is low. All these demonstrated that the proposed method could be applied in the class imbalance problem

Intelligent resource scheduling for 5G radio access network slicing

It is widely acknowledged that network slicing can tackle the diverse use cases and connectivity services of the forthcoming next-generation mobile networks (5G). Resource scheduling is of vital importance for improving resource-multiplexing gain among slices while meeting specific service requirements for radio access network (RAN) slicing. Unfortunately, due to the performance isolation, diversified service requirements, and network dynamics (including user mobility and channel states), resource scheduling in RAN slicing is very challenging. In this paper, we propose an intelligent resource scheduling strategy (iRSS) for 5G RAN slicing. The main idea of an iRSS is to exploit a collaborative learning framework that consists of deep learning (DL) in conjunction with reinforcement learning (RL). Specifically, DL is used to perform large time-scale resource allocation, whereas RL is used to perform online resource scheduling for tackling small time-scale network dynamics, including inaccurate prediction and unexpected network states. Depending on the amount of available historical traffic data, an iRSS can flexibly adjust the significance between the prediction and online decision modules for assisting RAN in making resource scheduling decisions. Numerical results show that the convergence of an iRSS satisfies online resource scheduling requirements and can significantly improve resource utilization while guaranteeing performance isolation between slices, compared with other benchmark algorithms

Application of the Microwave Technology to the Environmental Protection

The microwave irradiation technologies applied to environmental protection is surveyed. The mechanism and features of microwave irradiation and the microwave technologies applied to wastewater are emphasized especially. Waste gas and waste solid treatment, environmental protection materials production and environmental monitor and the problems of the technologies are discussed the applicable prospect of the microwave technology in the environmental protection.

Co-Check: Collaborative Outsourced Data Auditing in Multicloud Environment

With the increasing demand for ubiquitous connectivity, wireless technology has significantly improved our daily lives. Meanwhile, together with cloud-computing technology (e.g., cloud storage services and big data processing), new wireless networking technology becomes the foundation infrastructure of emerging communication networks. Particularly, cloud storage has been widely used in services, such as data outsourcing and resource sharing, among the heterogeneous wireless environments because of its convenience, low cost, and flexibility. However, users/clients lose the physical control of their data after outsourcing. Consequently, ensuring the integrity of the outsourced data becomes an important security requirement of cloud storage applications. In this paper, we present Co-Check, a collaborative multicloud data integrity audition scheme, which is based on BLS (Boneh-Lynn-Shacham) signature and homomorphic tags. According to the proposed scheme, clients can audit their outsourced data in a one-round challenge-response interaction with low performance overhead. Our scheme also supports dynamic data maintenance. The theoretical analysis and experiment results illustrate that our scheme is provably secure and efficient

Robust Stereoscopic Crosstalk Prediction

We propose a new metric to predict perceived crosstalk using the original images rather than both the original and ghosted images. The proposed metrics are based on color information. First, we extract a disparity map, a color difference map, and a color contrast map from original image pairs. Then, we use those maps to construct two new metrics (Vdispc and Vdlogc). Metric Vdispc considers the effect of the disparity map and the color difference map, while Vdlogc addresses the influence of the color contrast map. The prediction performance is evaluated using various types of stereoscopic crosstalk images. By incorporating Vdispc and Vdlogc, the new metric Vpdlc is proposed to achieve a higher correlation with the perceived subject crosstalk scores. Experimental results show that the new metrics achieve better performance than previous methods, which indicate that color information is one key factor for crosstalk visible prediction. Furthermore, we construct a new data set to evaluate our new metrics

Two Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin [preprint]

In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery and with the nuclear lamina, and generally display characteristics of constitutive heterochromatin, including late DNA replication, enrichment of H3K9me3 and little gene expression. In contrast, Type II NADs associate with nucleoli but do not overlap with LADs. Type II NADs tend to replicate earlier, display greater gene expression, and are more often enriched in H3K27me3 than Type I NADs. The nucleolar associations of both classes of NADs were confirmed via DNA-FISH, which also detected Type I but not Type II probes enriched at the nuclear lamina. Interestingly, Type II NADs are enriched in distinct gene classes, notably factors important for differentiation and development. In keeping with this, we observed that a Type II NAD is developmentally regulated, present in MEFs but not in undifferentiated embryonic stem (ES) cells

N6-Methyladenosine and Viral Infection

N6-methyladenosine (m6A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m6A. Multiple m6A-modified viral RNAs have been observed. The epitranscriptome of m6A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m6A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m6A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m6A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m6A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m6A in distinct viral infection. Given the increasingly important roles of m6A in diverse viruses, m6A represents a novel potential target for antiviral therapy