Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays

In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent, and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings

Energy Loss versus Shadowing in the Drell-Yan Reaction on Nuclei

We present a new analysis of the E772 and E866 experiments on the nuclear dependence of Drell-Yan (DY) lepton pair production resulting from the bombardment of $^2H$, Be, C, Ca, Fe, and W targets by 800 GeV/c protons at Fermilab. We employ a light-cone formulation of the DY reaction in the rest frame of the nucleus, where the dimuons detected at small values of Bjorken x_2 << 1 may be considered to originate from the decay of a heavy photon radiated from an incident quark in a bremsstrahlung process. We infer the energy loss of the quark by examining the suppression of the nuclear-dependent DY ratios seen as a function of projectile momentum fraction x_1 and dimuon mass M. Shadowing, which also leads to nuclear suppression of dimuons, is calculated within the same approach employing the results of phenomenological fits to deep inelastic scattering data from HERA. The analysis yields -dE/dz =2.73 +/- 0.37 +/- 0.5 GeV/fm for the rate of quark energy loss per unit path length, a value consistent with theoretical expectations including the effects of the inelastic interaction of the incident proton at the surface of the nucleus. This is the first observation of a nonzero energy loss effect in such experiments.Comment: 43 pages including 17 figure

Energy loss of fast quarks in nuclei

We report an analysis of the nuclear dependence of the yield of Drell-Yan dimuons from the 800 GeV/c proton bombardment of $^2H$, C, Ca, Fe, and W targets. Employing a new formulation of the Drell-Yan process in the rest frame of the nucleus, this analysis examines the effect of initial-state energy loss and shadowing on the nuclear-dependence ratios versus the incident proton's momentum fraction and dimuon effective mass. The resulting energy loss per unit path length is $-dE/dz = 2.32 \pm 0.52\pm 0.5$ GeV/fm. This is the first observation of a nonzero energy loss of partons traveling in nuclear environment.Comment: 5 pages, including 4 figure

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Lithographically Fabricated Micro-Reflectors for Sensitive Point of Care Diagnostics

Timely diagnosis and treatment of infectious diseases calls for highly sensitive diagnostic assays. Traditional diagnostic methods include microscopy, polymerase chain reaction (PCR), immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA). Many of these diagnostic methods, however, require complex sample processing steps or labels (typically a dye, enzyme or fluor) which can suffer from low signal strength or photo-bleaching (of fluors), and can require elaborate instrumentation for their detection. Here, we propose several diagnostic platforms utilizing lithographically-fabricated, micron-scale, reflective particles as novel, optical labels conjugated to antibodies. The particles, in the shape of cubes, serve as ultra-bright labels which are easily detectable using inexpensive, low-numerical aperture optics. The cubes, unlike traditional labels, are not susceptible to photo-bleaching and do not require any signal amplification. In this research work, we investigate the use of these novel particulate labels for the development of new immunoassay formats which are simple-to-use, cheap and possess sensitivities comparable to or better than well-established clinical diagnostic methods. First, the fabrication and use of suspended, micro-fabricated retroreflector cubes as optical labels will be demonstrated. The cubes will be used in a novel flotation format in which a low density polymer module acts as a capture surface. Antibody-functionalized cubes, bridged to the capture surface by the target present in the sample, are floated to the top of the sample where they can be observed and counted. In a second assay format the cubes, which are engineered to be denser than the sample matrix, are allowed to mix with the sample and fall to a detection surface within a reaction vessel. Simply inverting the vessel allows non-specifically bound cubes to fall away leaving behind specifically bound particles. Lastly, the use of these reflective particles in a centrifugal diagnostics format will be presented. Centrifugal forces are tailored to improve signal to background ratios by removing non-specifically bound particles in a highly controllable way.Chemical and Biomolecular Engineering, Department o

Pain assessment of the adult sedated and ventilated patients in the intensive care setting : a scoping review

Background: Pain is frequently encountered in the intensive care setting. Given the impact of pain assessment on patient outcomes and length of hospital stay, studies have been conducted to validate tools, establish guidelines and cast light on practices relating to pain assessment. Objective: To examine the extent, range and nature of the evidence around pain assessment practices in adult patients who cannot self-report pain in the intensive care setting and summarise the findings from a heterogenous body of evidence to aid in the planning and the conduct of future research and management of patient care. The specific patient cohort studied was the sedated/ ventilated patient within the intensive care setting. Design: A scoping review protocol utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping review checklist (PRISMA-ScR). Methods: The review comprised of five phases: identifying the research question, identifying relevant studies, study selection, charting the data and collating, summarizing, and reporting the results. Databases were systematically searched from January to April 2020. Databases included were Scopus, Web of Science, Medline via Ovid, CINAHL COMPLETE via EBSCO host, Health Source and PUBMED. Limits were applied on dates (2000 to current), language (English), subject (human) and age (adult). Key words used were “pain”, “assessment”, “measurement”, “tools”, “instruments”, “practices”, “sedated”, “ventilated”, “adult”. A hand search technique was used to search citations within articles. Database alerts were set to apprise the availability of research articles pertaining to pain assessment practices in the intensive care setting. Results: The review uncovered literature categorised under five general themes: behaviour pain assessment tools, pain assessment guidelines, position statements and quality improvement projects, enablers and barriers to pain assessment, and evidence appertaining to actual practices. Behaviour pain assessment tools are the benchmark for pain assessment of sedated and ventilated patients. The reliability and validity of physiologic parameters to assess pain is yet to be determined. Issues of compliance with pain assessment guidelines and tools exist and impact on practices. In some countries like Australia, there is a dearth of information regarding the prevalence and characteristics of patients receiving analgesia, type of analgesia used, pain assessment practices and the process of recording pain management. In general, pain assessment varies across different intensive care settings and lacks consistency. Conclusion: Research on pain assessment practices requires further investigation to explore the causative mechanisms that contribute to poor compliance with established pain management guidelines. The protocol of this review was registered with Open Science Framework (https://osf.io/25a6) Tweetable abstract: Pain assessment in intensive care settings lacks consistency. New information is needed to understand the causative mechanisms underpinning poor compliance with guidelines. © 202