Accurate Profiling of Microbial Communities from Massively Parallel Sequencing using Convex Optimization

We describe the Microbial Community Reconstruction ({\bf MCR}) Problem, which is fundamental for microbiome analysis. In this problem, the goal is to reconstruct the identity and frequency of species comprising a microbial community, using short sequence reads from Massively Parallel Sequencing (MPS) data obtained for specified genomic regions. We formulate the problem mathematically as a convex optimization problem and provide sufficient conditions for identifiability, namely the ability to reconstruct species identity and frequency correctly when the data size (number of reads) grows to infinity. We discuss different metrics for assessing the quality of the reconstructed solution, including a novel phylogenetically-aware metric based on the Mahalanobis distance, and give upper-bounds on the reconstruction error for a finite number of reads under different metrics. We propose a scalable divide-and-conquer algorithm for the problem using convex optimization, which enables us to handle large problems (with $\sim10^6$ species). We show using numerical simulations that for realistic scenarios, where the microbial communities are sparse, our algorithm gives solutions with high accuracy, both in terms of obtaining accurate frequency, and in terms of species phylogenetic resolution.Comment: To appear in SPIRE 1

Measurement of Electron Clouds in Large Accelerators by Microwave Dispersion

Clouds of low energy electrons in the vacuum beam pipes of accelerators of positively charged particle beams present a serious limitation for operation at high currents. Furthermore, it is difficult to probe their density over substantial lengths of the beam pipe. We have developed a novel technique to directly measure the electron cloud density via the phase shift induced in a TE wave transmitted over a section of the accelerator and used it to measure the average electron cloud density over a 50 m section in the positron ring of the PEP-II collider at the Stanford Linear Accelerator Center

Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

The Feeling of a Line: Nineteenth-Century American Literature and the Psychology of Imagination

This dissertation is about the psychology of imagination in the last two decades of the nineteenth century. In the critical account of this period, much has been written about the relation between literature and sight; it has hardly been noted, however, that the period was marked by the emergence of a field of research into a different kind of "vision" -- the images produced by words on a page. My dissertation addresses this gap in two ways: first, in an account of a major shift in the psychological understanding of the mind's eye in this period; second, in a series of readings which explore the ways in which writers and critics responded to this new science. Both accounts begin with Francis Galton's 1880 publication of "Statistics of Mental Imagery" -- the first study of its kind. His findings -- still cited by psychologists today -- disrupted the idea that words predictably or even reliably produced "pictures" in the mind, thus troubling more than a century of philosophic and literary debate over the nature of mental representation. As William James observed in 1890, Galton's study had "made an era in descriptive Psychology." After repeating Galton's investigation in his own classroom, James concluded that "There are imaginations, not `The Imagination,' and they must be studied in detail." My dissertation traces the work of a series of writers who drew upon this research. In chapters centered on Charlotte Perkins Gilman, Mark Twain, William James and Helen Keller -- all of whom were familiar with Galton's study -- I locate a literary tradition which found its value not in objective correspondence with the outside world, but rather, in the embodied feeling of the mind at work. These writers took from psychology the premise that mental vision, like physical vision, had limits -- limits defined by the body. While this limitation could be understood as a constriction, it also suggested the possibility that the imagination could take on the status of physical experience -- that the mechanical act of transforming shapes into signs could become a form of training for "real" life. In order to understand these texts, I argue, we must attend to what James described as the "half" of reading that is not present on the printed page -- the "half" provided by the reader him or herself. In pursuing this claim, I model a style of critical analysis that remains grounded in close reading, but that nevertheless seeks to account for the reader's imaginative experience. This style of reading critically re-orients our understanding of these texts, moving us away from "problem" plots and unresolved themes, towards larger structures of perception. These writers, I argue, do not seek to inform us about another person's experience; rather they provide us with a grammar of experience -- a technique for living intended to last well beyond the moment when the book is set aside

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD