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"Miller, Benjamin"
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Foundations of agnostic statistics
\"The last three decades have seen a marked change in the manner in which quantitative empirical inquiry in the social and health sciences is conducted. Sometimes dubbed the \"credibility revolution,\" this change has been characterized by a growing acknowledgment that the evidence that researchers adduce for their claims is often predicated on unsustainable assumptions. Our understanding of statistical and econometric tools has needed to change accordingly. We have found that conventional textbooks, which often begin with incredible modeling assumptions, are not well suited as a starting point for credible research\"-- Provided by publisher.
Book
COVID-19 Exposes the Cracks in Our Already Fragile Mental Health System
The coronavirus pandemic has caused enormous concern among many people. Every morning, we are met with an increasing deluge of dire news about the most recent number of people to contract COVID-19 and to die from it, decreases in the stock market, and countries implementing broad travel restrictions and stay-at-home orders.
The current state of affairs is having a negative effect on the mental well-being of our country's residents. It also highlights the policy gaps in our current system that inhibit the vital conditions for well-being and resiliency.
Although the primary focus has rightfully been on stopping the spread of COVID-19, we should also quickly prepare to address the mental toll the pandemic is taking on individuals and communities across the country. (
. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305699).
Journal Article
The foragers of Point Hope : the biology and archaeology of humans on the edge of the Alaskan arctic
\"On the edge of the Arctic Ocean, above the Arctic Circle, the prehistoric settlements at Point Hope, Alaska, represent a truly remarkable accomplishment in human biological and cultural adaptations. Presenting a set of anthropological analyses on the human skeletal remains and cultural material from the Ipiutak and Tigara archaeological sites, The Foragers of Point Hope sheds new light on the excavations from 1939-41, which provided one of the largest sets of combined biological and cultural materials of northern latitude peoples in the world. A range of material items indicated successful human foraging strategies in this harsh Arctic environment. They also yielded enigmatic artifacts indicative of complex human cultural life filled with dense ritual and artistic expression. These remnants of past human activity contribute to a crucial understanding of past foraging lifeways and offer important insights into the human condition at the extreme edges of the globe\"-- Provided by publisher.
Book
RNA G-quadruplex structure contributes to cold adaptation in plants
Nucleotide composition is suggested to infer gene functionality and ecological adaptation of species to distinct environments. However, the underlying biological function of nucleotide composition dictating environmental adaptations is largely unknown. Here, we systematically analyze the nucleotide composition of transcriptomes across 1000 plants (1KP) and their corresponding habitats. Intriguingly, we find that plants growing in cold climates have guanine (G)-enriched transcriptomes, which are prone to forming RNA G-quadruplex structures. Both immunofluorescence detection and in vivo structure profiling reveal that RNA G-quadruplex formation in plants is globally enhanced in response to cold. Cold-responsive RNA G-quadruplexes strongly enhanced mRNA stability, rather than affecting translation. Disruption of individual RNA G-quadruplex promotes mRNA decay in the cold, leading to impaired plant cold response. Therefore, we propose that plants adopted RNA G-quadruplex structure as a molecular signature to facilitate their adaptation to the cold during evolution.
During evolution, plants have adapted to habitats with distinct temperature ranges. In this study, scientists report that a specific RNA structure motif, RNA G-quadruplex (RG4) is enriched across genomes of plant species growing in colder climates.
Journal Article
Digital technologies in the public-health response to COVID-19
Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases.
The COVID-19 pandemic has resulted in an accelerated development of applications for digital health, including symptom monitoring and contact tracing. Their potential is wide ranging and must be integrated into conventional approaches to public health for best effect.
Journal Article
Optogenetic control of gene expression in plants in the presence of ambient white light
Optogenetics is the genetic approach for controlling cellular processes with light. It provides spatiotemporal, quantitative and reversible control over biological signaling and metabolic processes, overcoming limitations of chemically inducible systems. However, optogenetics lags in plant research because ambient light required for growth leads to undesired system activation. We solved this issue by developing plant usable light-switch elements (PULSE), an optogenetic tool for reversibly controlling gene expression in plants under ambient light. PULSE combines a blue-light-regulated repressor with a red-light-inducible switch. Gene expression is only activated under red light and remains inactive under white light or in darkness. Supported by a quantitative mathematical model, we characterized PULSE in protoplasts and achieved high induction rates, and we combined it with CRISPR–Cas9-based technologies to target synthetic signaling and developmental pathways. We applied PULSE to control immune responses in plant leaves and generated
Arabidopsis
transgenic plants. PULSE opens broad experimental avenues in plant research and biotechnology.
PULSE is an optogenetic tool that consists of two modules with different wavelength sensitivities. Their interplay enables optogenetic access to gene expression in plants independently of ambient light.
Journal Article
Arrayed Imaging Reflectometry monitoring of anti-viral antibody production throughout vaccination and breakthrough Covid-19
Immune responses to COVID-19 infection and vaccination are individual and varied. There is a need to understand the timeline of vaccination efficacy against current and yet to be discovered viral mutations. Assessing immunity to SARS-CoV-2 in the context of immunity to other respiratory viruses is also valuable. Here we demonstrate the capability of a fully automated prototype Arrayed Imaging Reflectometry system to perform reliable longitudinal serology against a 34-plex respiratory array. The array contains antigens for respiratory syncytial virus, seasonal influenza, common human coronaviruses, MERS, SARS-CoV-1, and SARS-CoV-2. AIR measures a change in reflectivity due to the binding of serum antibodies to the antigens on the array. Samples were collected from convalescent COVID-19 donors and individuals vaccinated with a two-dose mRNA vaccine regimen. Vaccinated samples were collected prior to the first dose, one week after the first dose, one week after the second dose, and monthly thereafter. Information following booster dose and/or breakthrough infection is included for a subset of subjects. Longitudinal samples of vaccinated individuals demonstrate a rise and fall of SARS-CoV-2 spike antibodies in agreement with general knowledge of the adaptive immune response and other studies. Linear Regression analysis was performed to understand the relationship between antibodies binding to different antigens on the array. Our analysis identified strong correlations between closely related influenza virus strains as well as correlations between SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. A small test of using diluted whole blood from a fingerstick provided clean arrays with antibody binding comparable to serum. Potential applications include assessing immunity in the context of exposure to multiple respiratory viruses, clinical serology, population monitoring to facilitate public health recommendations, and vaccine development against new viruses and virus mutations.
Journal Article
Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination
While mRNA vaccines have been well-studied in vitro and in animals prior to their use in the human population during the Covid-19 pandemic, their exact mechanisms of inducing immunity are still being elucidated. The large-scale collection of data necessary to fully understand these mechanisms, and their variability across heterogeneous populations, requires rapid diagnostic tests that accurately measure the various biomarkers involved in the immune response following vaccination. Recently, our lab developed a novel “Disposable Photonics” platform for rapid, label-free, scalable diagnostics that utilizes photonic ring resonator sensor chips combined with plastic micropillar cards able to provide passive microfluidic flow. Here, we demonstrate the utility of this system in confirming the presence of SARS-CoV-2 spike protein in the serum of recently vaccinated subjects, as well as tracking a post-vaccination rise in anti-SARS-CoV-2 antibodies. A maximum concentration in SARS-CoV-2 spike protein was detected one day after vaccination and was reduced below detectable levels within 10 days. This highlights the applicability of our rapid photonic sensor platform for acquiring the data necessary to understand vaccine mechanisms on a large scale, as well as individual patient responses to SARS-CoV-2 mRNA vaccines.
Journal Article
Waveguide-Enhanced Raman Spectroscopy (WERS): An Emerging Chip-Based Tool for Chemical and Biological Sensing
Photonic chip-based methods for spectroscopy are of considerable interest due to their applicability to compact, low-power devices for the detection of small molecules. Waveguide-enhanced Raman spectroscopy (WERS) has emerged over the past decade as a particularly interesting approach. WERS utilizes the evanescent field of a waveguide to generate Raman scattering from nearby analyte molecules, and then collects the scattered photons back into the waveguide. The large interacting area and strong electromagnetic field provided by the waveguide allow for significant enhancements in Raman signal over conventional approaches. The waveguide can also be coated with a molecular class-selective sorbent material to concentrate the analyte, thus further increasing the Raman signal. This review provides an overview of the historical development of WERS and highlights recent theoretical and experimental achievements with the technique.
Journal Article
Real-Time, Continuous Monitoring of Tissue Chips as an Emerging Opportunity for Biosensing
Tissue chips (TCs), otherwise known as organs-on-a-chip (OoC), organ chips (OCs), or microphysiological systems (MPS), are rapidly gaining prominence as an extension of or even replacement for traditional animal models of disease physiology. They also have recognized utility in the context of drug development: for example, data from TCs can now be submitted in place of some animal testing to the FDA. In principle, TCs are structured to allow measurement of any number of outputs that yield information about the tissue. However, to date, measurements made during experiments with TCs have been largely restricted to immunofluorescence microscopy and benchtop assays performed on media extracted from the cell culture within the device. With the development of biosensors that are sensitive and have an ever-shrinking footprint, on-board biosensing is now in the early stages of exploration. This review discusses the importance of tissue chips and the advances in sensing that will aid the complexity and utility of tissue chip research moving forward. We cover several sensing modalities, including electrical and optical sensing modes. Finally, challenges and opportunities for the future are discussed.
Journal Article