A network approach for managing and processing big cancer data in clouds

Translational cancer research requires integrative analysis of multiple levels of big cancer data to identify and treat cancer. In order to address the issues that data is decentralised, growing and continually being updated, and the content living or archiving on different information sources partially overlaps creating redundancies as well as contradictions and inconsistencies, we develop a data network model and technology for constructing and managing big cancer data. To support our data network approach for data process and analysis, we employ a semantic content network approach and adopt the CELAR cloud platform. The prototype implementation shows that the CELAR cloud can satisfy the on-demanding needs of various data resources for management and process of big cancer data

A Case-control Study of Haemorrhagic Septicaemia in Buffaloes and Cattle in Karachi, Pakistan, in 2012

A retrospective epidemiological case–control study was performed in Karachi, Pakistan, from January to April 2013. The owners of 217 dairy cattle and buffalo farms from six different locations in Karachi were interviewed. The aim of the study was to identify risk factors associated with the presence of haemorrhagic septicaemia (HS). Farms with a history of at least one instance of sudden death in a dairy animal during 2012 and a positive clinical HS diagnosis (made by local veterinarians) were defined as cases. Farms having no history of sudden deaths in 2012 were defined as controls. Univariable analyses were initially conducted, and factors with P ≤ 0.25 were offered to a multivariable logistic regression model to identify putative risk factors. The final multivariable logistic model contained five factors. Vaccination was found to be a protective factor (OR = 0.22) along with the length of time cattle were kept on farm (months). For every extra month cattle were kept, the odds of HS disease were reduced by a factor of 0.9. In contrast, for every extra animal in a herd, the risk of infection increased by a factor of 1.01. Supplying underground water and the presence of foot and mouth disease on the farm increased the risk by 2.90 and 2.37, respectively. To understand the epidemiology of HS in Karachi dairy herds, more in-depth research is required to study the risk and protective factors identified in this survey and to evaluate risk mitigation strategies, where possible

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany

Security and Privacy Issues in Wireless Mesh Networks: A Survey

This book chapter identifies various security threats in wireless mesh network (WMN). Keeping in mind the critical requirement of security and user privacy in WMNs, this chapter provides a comprehensive overview of various possible attacks on different layers of the communication protocol stack for WMNs and their corresponding defense mechanisms. First, it identifies the security vulnerabilities in the physical, link, network, transport, application layers. Furthermore, various possible attacks on the key management protocols, user authentication and access control protocols, and user privacy preservation protocols are presented. After enumerating various possible attacks, the chapter provides a detailed discussion on various existing security mechanisms and protocols to defend against and wherever possible prevent the possible attacks. Comparative analyses are also presented on the security schemes with regards to the cryptographic schemes used, key management strategies deployed, use of any trusted third party, computation and communication overhead involved etc. The chapter then presents a brief discussion on various trust management approaches for WMNs since trust and reputation-based schemes are increasingly becoming popular for enforcing security in wireless networks. A number of open problems in security and privacy issues for WMNs are subsequently discussed before the chapter is finally concluded.Comment: 62 pages, 12 figures, 6 tables. This chapter is an extension of the author's previous submission in arXiv submission: arXiv:1102.1226. There are some text overlaps with the previous submissio

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The evolution of H5N1 has attracted significant interest 1-4 due to linkages with avian 5,6 and human infections 7,8. The basic tenets of influenza genetics 9 attribute genetic drift to replication errors caused by a polymerase complex that lacks a proof reading function. However, recent analysis 10 of swine influenza genes identifies regions copied with absolute fidelity for more than 25 years. In addition, polymorphism tracing of clade 2.2 H5N1 single nucleotide polymorphisms identify concurrent acquisition 11 of the same polymorphism onto multiple genetic backgrounds in widely dispersed geographical locations. Here we show the aggregation of regional clade 2.2 polymorphisms from Germany, Egypt, and sub-Sahara Africa onto a human Nigerian H5N1 hemagglutinin (HA), implicating recombination in the dispersal and aggregation of single nucleotide polymorphisms from closely related genomes

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Learning to Obtain Reward, but Not Avoid Punishment, Is Affected by Presence of PTSD Symptoms in Male Veterans: Empirical Data and Computational Model

Post-traumatic stress disorder (PTSD) symptoms include behavioral avoidance which is acquired and tends to increase with time. This avoidance may represent a general learning bias; indeed, individuals with PTSD are often faster than controls on acquiring conditioned responses based on physiologically-aversive feedback. However, it is not clear whether this learning bias extends to cognitive feedback, or to learning from both reward and punishment. Here, male veterans with self-reported current, severe PTSD symptoms (PTSS group) or with few or no PTSD symptoms (control group) completed a probabilistic classification task that included both reward-based and punishment-based trials, where feedback could take the form of reward, punishment, or an ambiguous “no-feedback” outcome that could signal either successful avoidance of punishment or failure to obtain reward. The PTSS group outperformed the control group in total points obtained; the PTSS group specifically performed better than the control group on reward-based trials, with no difference on punishment-based trials. To better understand possible mechanisms underlying observed performance, we used a reinforcement learning model of the task, and applied maximum likelihood estimation techniques to derive estimated parameters describing individual participants’ behavior. Estimations of the reinforcement value of the no-feedback outcome were significantly greater in the control group than the PTSS group, suggesting that the control group was more likely to value this outcome as positively reinforcing (i.e., signaling successful avoidance of punishment). This is consistent with the control group’s generally poorer performance on reward trials, where reward feedback was to be obtained in preference to the no-feedback outcome. Differences in the interpretation of ambiguous feedback may contribute to the facilitated reinforcement learning often observed in PTSD patients, and may in turn provide new insight into how pathological behaviors are acquired and maintained in PTSD

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury