Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials

The increasing use of multi-walled carbon nanotubes (MWCNTs) in consumer products and their potential to induce adverse lung effects following inhalation has lead to much interest in better understanding the hazard associated with these nanomaterials (NMs). While the current regulatory requirement for substances of concern, such as MWCNTs, in many jurisdictions is a 90-day rodent inhalation test, the monetary, ethical, and scientific concerns associated with this test led an international expert group to convene in Washington, DC, USA, to discuss alternative approaches to evaluate the inhalation toxicity of MWCNTs. Pulmonary fibrosis was identified as a key adverse outcome linked to MWCNT exposure, and recommendations were made on the design of an in vitro assay that is predictive of the fibrotic potential of MWCNTs. While fibrosis takes weeks or months to develop in vivo, an in vitro test system may more rapidly predict fibrogenic potential by monitoring pro-fibrotic mediators (e.g., cytokines and growth factors). Therefore, the workshop discussions focused on the necessary specifications related to the development and evaluation of such an in vitro system. Recommendations were made for designing a system using lung-relevant cells co-cultured at the air–liquid interface to assess the pro-fibrogenic potential of aerosolized MWCNTs, while considering human-relevant dosimetry and NM life cycle transformations. The workshop discussions provided the fundamental design components of an air–liquid interface in vitro test system that will be subsequently expanded to the development of an alternative testing strategy to predict pulmonary toxicity and to generate data that will enable effective risk assessment of NMs

Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis

Structural characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from B. bovis in the apo state and complexed with antifolate inhibitors in both enzymatic active sites is reported

The Semantic Reader Project: Augmenting Scholarly Documents through AI-Powered Interactive Reading Interfaces

Scholarly publications are key to the transfer of knowledge from scholars to others. However, research papers are information-dense, and as the volume of the scientific literature grows, the need for new technology to support the reading process grows. In contrast to the process of finding papers, which has been transformed by Internet technology, the experience of reading research papers has changed little in decades. The PDF format for sharing research papers is widely used due to its portability, but it has significant downsides including: static content, poor accessibility for low-vision readers, and difficulty reading on mobile devices. This paper explores the question "Can recent advances in AI and HCI power intelligent, interactive, and accessible reading interfaces -- even for legacy PDFs?" We describe the Semantic Reader Project, a collaborative effort across multiple institutions to explore automatic creation of dynamic reading interfaces for research papers. Through this project, we've developed ten research prototype interfaces and conducted usability studies with more than 300 participants and real-world users showing improved reading experiences for scholars. We've also released a production reading interface for research papers that will incorporate the best features as they mature. We structure this paper around challenges scholars and the public face when reading research papers -- Discovery, Efficiency, Comprehension, Synthesis, and Accessibility -- and present an overview of our progress and remaining open challenges

The human sodium iodide symporter as a reporter gene for studying Middle East respiratory syndrome coronavirus pathogenesis

Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six in vitro passages, and were functional. Further in vivo evaluation indicated variable stability, but resolution limits hampered in vivo functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease.IMPORTANCE Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus

Design and characterization of the SPT-3G receiver

The SPT-3G receiver was commissioned in early 2017 on the 10-meter South Pole Telescope (SPT) to map anisotropies in the cosmic microwave background (CMB). New optics, detector, and readout technologies have yielded a multichroic, high-resolution, low-noise camera with impressive throughput and sensitivity, offering the potential to improve our understanding of inflationary physics, astroparticle physics, and growth of structure. We highlight several key features and design principles of the new receiver, and summarize its performance to date

Impact of electrical contacts design and materials on the stability of Ti superconducting transition shape

The South Pole Telescope SPT-3G camera utilizes Ti/Au transition edge sensors (TESs). A key requirement for these sensors is reproducibility and long-term stability of the superconducting (SC) transitions. Here, we discuss the impact of electrical contacts design and materials on the shape of the SC transitions. Using scanning electron microscope, atomic force microscope, and optical differential interference contrast microscopy, we observed the presence of unexpected defects of morphological nature on the titanium surface and their evolution in time in proximity to Nb contacts. We found direct correlation between the variations of the morphology and the SC transition shape. Experiments with different diffusion barriers between TES and Nb leads were performed to clarify the origin of this problem. We have demonstrated that the reproducibility of superconducting transitions can be significantly improved by preventing diffusion processes in the TES–leads contact areas

Performance and characterization of the SPT-3G digital frequency-domain multiplexed readout system using an improved noise and crosstalk model

The third-generation South Pole Telescope camera (SPT-3G) improves upon its predecessor (SPTpol) by an order of magnitude increase in detectors on the focal plane. The technology used to read out and control these detectors, digital frequency-domain multiplexing (DfMUX), is conceptually the same as used for SPTpol, but extended to accommodate more detectors. A nearly 5× expansion in the readout operating bandwidth has enabled the use of this large focal plane, and SPT-3G performance meets the forecasting targets relevant to its science objectives. However, the electrical dynamics of the higher-bandwidth readout differ from predictions based on models of the SPTpol system due to the higher frequencies used and parasitic impedances associated with new cryogenic electronic architecture. To address this, we present an updated derivation for electrical crosstalk in higher-bandwidth DfMUX systems and identify two previously uncharacterized contributions to readout noise, which become dominant at high bias frequency. The updated crosstalk and noise models successfully describe the measured crosstalk and readout noise performance of SPT-3G. These results also suggest specific changes to warm electronics component values, wire-harness properties, and SQUID parameters, to improve the readout system for future experiments using DfMUX, such as the LiteBIRD space telescope

Using Alternative Strategies and Approaches to Improve Hospital Throughput

Purpose: This quality improvement project aimed to create a standardized process to improve hospital throughput and decrease the length of stay through the support of multidisciplinary teams at Banner University Medical Center Tucson. Background: Hospitals across the country have experienced crowding and high patient volumes. This problem has existed in hospitals over the last 30 years but continues to worsen. The global pandemic of COVID-19 has put an additional unforeseen strain on top of a preexisting issue, exacerbating crowding, patient wait times, and increased hospital length of stay. Hospitals are strained to provide care to meet their patient demands and require alternate strategies to provide process improvement to meet these needs. Methods: Building upon ongoing improvement projects already in place at Banner University Medical Center Tucson, a multidisciplinary team was formed, aided by a tool to guide hospital throughput. This team collaborated through daily meetings using this tool to demonstrate demand and capacity within the hospital to focus efforts, ask pointed questions and decrease the length of stay. Results: This project was implemented over the course of one week and length of stay data was then gathered after completion. The length of stay results from the project implementation dates was 4.93, which is a 20% reduction from the highest length of stay seen in 2021, 5.22