Syndromic and Point-of-Care Molecular Testing

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic

Viral Infections

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Despite major advances in basic and applied research and the availability of several vaccines, viral diseases still account for a large proportion of the human infectious disease burden. Many viruses cause self-limiting and relatively mild infections, but several, including human immunodeficiency virus and influenza virus, are responsible for millions of deaths every year throughout the world. Several factors contribute to the enormous impact that viruses have on human health. For example, there are very few therapeutic options available for the treatment of viral infections, and many of those that are available possess a limited spectrum of activity or are designed for the treatment of diseases caused by specific viruses (e.g., oseltamivir is intended for the treatment of influenza only). In addition, the rapid evolution of viruses has led to the emergence of drug-resistant strains against which no currently available therapeutics are effective. Coupled with these and other issues are the appearance of never before seen viruses and the emergence of known but previously underappreciated viruses. Since the beginning of the twenty-first century, numerous “new” viruses, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the 2009 pandemic influenza A virus, and Lujo hemorrhagic fever virus, have made their debut and have proved to be formidable threats to human health. Recently, the appearance of Ebola virus (Zaire ebolavirus) in West Africa, a region that has not previously seen an outbreak of this virus, was marked by an epidemic that afflicted nearly 30,000 individuals and killed more than 11,000 of those who were infected. Most recently, the far-reaching and rapid spread of Zika virus, a mosquito-borne virus that was discovered in the 1940s in Uganda, in the Western Hemisphere has invoked considerable public and scientific attention and has given rise to perhaps the largest concerted effort by scientists to rapidly develop a vaccine to halt the transmission of a virus. Each of these points underscores the importance of further research into improved surveillance, diagnosis, treatment, and prevention of viral diseases

Single Particle Tracking: Analysis Techniques for Live Cell Nanoscopy.

Single molecule experiments are a set of experiments designed specifically to study the properties of individual molecules. It has only been in the last three decades where single molecule experiments have been applied to the life sciences; where they have been successfully implemented in systems biology for probing the behaviors of sub-cellular mechanisms. The advent and growth of super-resolution techniques in single molecule experiments has made the fundamental behaviors of light and the associated nano-probes a necessary concern among life scientists wishing to advance the state of human knowledge in biology. This dissertation disseminates some of the practices learned in experimental live cell microscopy. The topic of single particle tracking is addressed here in a format that is designed for the physicist who embarks upon single molecule studies. Specifically, the focus is on the necessary procedures to generate single particle tracking analysis techniques that can be implemented to answer biological questions. These analysis techniques range from designing and testing a particle tracking algorithm to inferring model parameters once an image has been processed. The intellectual contributions of the author include the techniques in diffusion estimation, localization filtering, and trajectory associations for tracking which will all be discussed in detail in later chapters. The author of this thesis has also contributed to the software development of automated gain calibration, live cell particle simulations, and various single particle tracking packages. Future work includes further evaluation of this laboratory\u27s single particle tracking software, entropy based approaches towards hypothesis validations, and the uncertainty quantification of gain calibration

The Use of Intelligent Systems for Planning and Scheduling of Product Development Projects

AbstractThe paper investigates the use of intelligent systems to identify the factors that significantly influence the duration of new product development. These factors are identified on the basis of an internal database of a production enterprise and further used to estimate the duration of phases in product development projects. In the paper, some models and methodologies of the knowledge discovery process are compared and a method of knowledge acquisition from an internal database is proposed. The presented approach is dedicated to industrial enterprises that develop modifications of previous products and are interested in obtaining more precise estimates for project planning and scheduling. The example contains four stages of the knowledge discovery process including data selection, data transformation, data mining, and interpretation of patterns. The example also presents a performance comparison of intelligent systems in the context of variable reduction and preprocessing. Among data mining techniques, artificial neural networks and the fuzzy neural system are chosen to seek relationships between the duration of project phase and other data stored in the information system of an enterprise

A Comprehensive Systems Biology Approach to Studying Zika Virus

Zika virus (ZIKV) is responsible for an ongoing and intensifying epidemic in the Western Hemisphere. We examined the complete predicted proteomes, glycomes, and selectomes of 33 ZIKV strains representing temporally diverse members of the African lineage, the Asian lineage, and the current outbreak in the Americas. Derivation of the complete selectome is an 'omics' approach to identify distinct evolutionary pressures acting on different features of an organism. Employment of the M8 model did not show evidence of global diversifying selection acting on the ZIKV polyprotein; however, a mixed effect model of evolution showed strong evidence (P<0.05) for episodic diversifying selection acting on specific sites. Single nucleotide polymorphisms (SNPs) were predictably frequent across strains relative to the derived consensus sequence. None of the 9 published detection procedures utilize targets that share 100% identity across the 33 strains examined, indicating that ZIKV escape from molecular detection is predictable. The predicted O-linked glycome showed marked diversity across strains; however, the N-linked glycome was highly stable. All Asian and American strains examined were predicted to include glycosylation of E protein ASN154, a modification proposed to mediate neurotropism, whereas the modification was not predicted for African strains. SNP diversity, episodic diversifying selection, and differential glycosylation, particularly of ASN154, may have major biological implications for ZIKV disease. Taken together, the systems biology perspective of ZIKV indicates: a.) The recently emergent Asian/American N-glycotype is mediating the new and emerging neuropathogenic potential of ZIKV; and b.) further divergence at specific sites is predictable as endemnicity is established in the Americas