Microbial Colonization Drives Expansion of IL-1 Receptor 1-Expressing and IL-17-Producing γ/δ T Cells

SummaryIL-17 cytokine production by the Th17 T cell subset is regulated by intestinal commmensals. We show that microbial colonization also regulates innate IL-17 production. A population of CD62L− γ/δ T cells, in particular a lineage expressing the IL-1 receptor 1 (IL-1R1), can be quickly activated by microbes to produce IL-17. Antibiotic treatment and monocolonization of mice suggest that specific commensals—but not metronidazole-sensitive anaerobes like Bacteroides species—are required for maintaining IL-1R1+ γ/δ T cells. Signaling through the guanine nucleotide exchange factor VAV1, but not through Toll-like receptors or antigen presentation pathways, is essential for inducing IL-1R1+ γ/δ T cells. Furthermore, IL-1R1+ γ/δ T cells are a potential source of IL-17 that can be activated by IL-23 and IL-1 in both infectious and noninfectious settings in vitro and in vivo. Thus, commensals orchestrate the expansion of phenotypically distinct γδ T cells, and innate immunity is a three-way interaction between host, pathogens, and microbiota

The Combinatorics of Cache Misses during Matrix Multiplication

In this paper we construct an analytic model of cache misses during matrix multiplication. The analysis in this paper applies to square matrices of size 2m where the array layout function is given in terms of a function Θ that interleaves the bits in the binary expansions of the row and column indices. We first analyze the number of cache misses for direct-mapped caches and then indicate how to extend this analysis to -way associative caches. The work in this paper accomplishes two things. First, we construct fast algorithms to estimate the number of cache misses. Second, we develop a theoretical understanding of cache misses that will allow us, in subsequent work, to approach the problem of minimizing cache misses by appropriately choosing the bit interleaving function that goes into the array layout function

Role of visual analytics in supporting mental healthcare systems research and policy: A systematic scoping review

The availability of healthcare data has exponentially grown, both in quantity and complexity. The speed of this evolution has generated new challenges for translating complex data into effective evidence-informed policy. Visual analytics offers new capacity to analyze healthcare systems and support better decision-making. We conducted a systematic scoping review to look for evidence of visual analytics approaches being applied to mental healthcare systems and their use in driving policy. We found 79 relevant studies and categorized them in two ways: by study purpose and by type of visualization. The majority (67.1%) of the studies used geographical maps, and 11% conducted highly complex studies requiring novel visualizations. Significantly, only 15% of the studies provided information indicating high levels of usability for policy and planning. Our findings suggest that while visual analytics continues to evolve rapidly, there is a need to ensure this evolution reflects the practical needs of policy makers

Recycling of dissolved iron in the North Pacific Subtropical Gyre

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hawco, N. J., Yang, S.-C., Pinedo-Gonzalez, P., Black, E. E., Kenyon, J., Ferron, S., Bian, X., & John, S. G. Recycling of dissolved iron in the North Pacific Subtropical Gyre. Limnology and Oceanography, 67(11), (2022): 2448-2465, https://doi.org/10.1002/lno.12212.The importance of iron as a limiting nutrient in the open ocean is widely recognized, but there is substantial uncertainty about the rate that it cycles in the marine environment. Here, we combine measurements from the water column, sediment traps, and incubations to constrain Fe turnover during summer at Station ALOHA in the North Pacific Subtropical Gyre. Using low levels of 57Fe–58Fe double spike, measured with high precision by multi-collector inductively coupled plasma mass spectrometry, we find Fe uptake rates of 30–60 pM d−1 throughout the euphotic zone. Dissolved Fe turnover times are estimated at 10–15 d in the mixed layer and 1–3 d near the deep chlorophyll maximum. Aerosol Fe supply inferred from a thorium isotope mass balance indicates that the dissolved Fe residence time is approximately 6 months in the upper euphotic zone (0–75 m), relative to external sources, and 2 months in the lower euphotic zone (75–150 m). To reconcile these observations, the average Fe atom must be recycled over 25 times at Station ALOHA in both the upper and lower euphotic zones (an “Fe ratio” equal to 0.04 and 0.03, respectively), a level of conservation that has only been documented in Fe-limited regions thus far. At steady state, this scenario requires an aerosol Fe solubility of 4.5%, which is similar to dissolution experiments from Pacific Ocean aerosols. Our results suggest that the oligotrophic ocean is capable of recycling iron efficiently even when these ecosystems are not demonstrably iron-limited.This work was also supported by the Simons Foundation (602538 and 823167 to N.J.H., 329108 to S.G.J) and National Science Foundation grants 2022969 to N.J.H. and 1911990 to S.F

A Conversation on Automation and Agency

Industrial robotics and the hardware and software of automation have been at the center of the discourse on computational design and digital fabrication for more than a decade. Initially developed for the execution of repetitive tasks in the context of serialized production and manufacturing, robots and industrial machines have been repurposed, reprogrammed, and rethought for an array of new tasks, as well as new approaches to what they can do and what they can represent. However, the meaning, histories, and array of metaphors surrounding robots inform design and creative practice. This keynote conversation brought together five designers, scholars, artists, and practitioners whose work engages with robotics and automation, specifically focusing on their implications in design and creative practice, and their complex cultural and political histories

A Collaborative Clearinghouse for Data Management Training and Education Resources

Objective: The main objectives of this breakout session are for the Data Management Training (DMT) Clearinghouse team to: 1) introduce the Clearinghouse and its current design and implementation, 2) solicit submissions to its learning resource inventory, and 3) collect feedback upon its web interface and future development. Features of the Clearinghouse that will be demonstrated include how to search and browse its inventory as well as submit a learning resource to the Clearinghouse using the LRMI (Learning Resource Metadata Initiative) metadata format. The team will also share the roadmap for the Clearinghouse’s upcoming features. In order to provide feedback regarding the Clearinghouse’s usability, the team will invite the session attendees to test the Clearinghouse’s services and will encourage comments to guide its future development. Setting/Participants/Resources: Since the DMT Clearinghouse is entirely accessible via the web, in order to demonstrate the Clearinghouse successfully, a reliable (and preferably free of charge) internet connection, and an overhead projecting capability will need to be available to the presenter. It would also be very useful for the attendees of the session to have access to the same internet connection, so that if they desire, the attendees can follow along with the steps of the demonstration, and contribute to the Clearinghouse inventory. The main presenter will plan to bring her own laptop with built-in standard HDMI and USB ports. As a result, it will be helpful if a HDMI or USB cable could also be provided for the presenter to connect her laptop to the projecting equipment. Method: Many research organizations, government agencies, and academic institutions have been developing excellent learning resources in order to support and meet the needs for data management training. However, these learning resources are often hosted on various websites and spread across various scientific domains. Consequently, these resources can be difficult to locate, especially by those who are not already familiar with the creators/authors. This is a barrier to the use and reuse of these resources, and can have significant impact on the promotion and propagation of best practices for data management. To address this need within the Earth sciences, the U.S. Geological Survey’s (USGS) Community for Data Integration (CDI), the Federation of Earth Science Information Partners (ESIP), and the Data Observation Network for Earth (DataONE) have collaborated to create a web-based Clearinghouse1 for collecting data management learning resources that are focused on the Earth sciences. The initial seed funding for the effort was provided by a grant received from the USGS CDI earlier in 2016, and ESIP’s Drupal site provided the hosting infrastructure for the Clearinghouse. Members from the USGS, DataONE, ESIP’s Data Stewardship Committee and its Data Management Training Working Group, Knowledge Motifs LLC, as well as Blue Dot Lab met regularly between April and October, 2016 in order to discuss, create, and implement the content structure and infrastructure components necessary to build the current revision of the Clearinghouse. 1. http://dmtclearinghouse.esipfed.org Results: As a registry of information about the educational resources on topics related to research data management (initially focused on Earth sciences), the Clearinghouse serves as a centralized location for searching or browsing an inventory of these learning resources. Currently, the Clearinghouse offers search and browse functionality that is open to all, and submission of information about educational resources by login with a free ESIP account. To assist with discoverability, the learning resources are described using Learning Resource Metadata Initiative (LRMI) schema. Additionally, the resources may be associated with the steps of data and research life cycles, such as the USGS CDI’s Science Support Framework2 and DataONE’s Data Life Cycle3. Leveraging the team’s collective experience in creating, presenting and distributing data management learning resources, the Clearinghouse included the learning resources from USGS, ESIP, and DataONE as its initial inventory, but is expanding to resources from NASA and others. Crowdsourcing is currently the main mechanism for sustaining the Clearinghouse. Going forward, in addition to the built-in workflow to allow anyone from the public to submit descriptive information about the data management learning resources that s/he wishes to share, future capabilities will be added to enable contributions to review, edit, and rank the submissions, as desired. 2. https://my.usgs.gov/confluence/display/cdi/CDI+Science+Support+Framework3. https://www.dataone.org/data-life-cycle Discussion/Conclusion: The DMT Clearinghouse team was successful in completing the initial development phase as scheduled for the first six months of its funding, including some informal usability testing of the interface. The team aims to continue to develop and enhance the Clearinghouse’s capabilities, including the evaluation of its usability, through collaboration with additional communities, and if feasible, adding the capability for bulk-loading of learning resources. Being able to present the Clearinghouse at the eScience Symposium would not only allow those who are involved with or would like to learn about data management to leverage the Clearinghouse’s resources, but also connect those who would like to contribute to the project with the Clearinghouse team. Ultimately, the Clearinghouse is designed so that the resources from its inventory could be used in a variety of data management training and education environments. By exposing the Clearinghouse to diverse users and communities, the Clearinghouse team can better assess how the Clearinghouse can be updated and what technological enhancements to pursue in the future in order to improve our support of research data management training needs

Nod2 Suppresses Borrelia burgdorferi Mediated Murine Lyme Arthritis and Carditis through the Induction of Tolerance

The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM) resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP), resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance

High-Transmission-Efficiency and Side-Viewing Micro OIDRS Probe for Fast and Minimally Invasive Tumor Margin Detection

The determination of a cancer free margin I organ is a difficult and time consuming process, with an unmet need for rapid determination of tumor margin at surgery. In this paper, we report the design, fabrication, and testing of a novel miniaturized optical sensor probe with “side-viewing” capability. Its unprecedented small size, unique “side-viewing” capability, and high optical transmission efficiency enable the agile maneuvering and efficient data collection even in the narrow cavities inside the human body. The sensor probe consists of four micromachined substrates with optical fibers for oblique light incidence and collection of spatially resolved diffuse reflectance from the contacted tissues. The optical sensor probe has been used to conduct the oblique incidence diffuse reflectance spectroscopy (OIDRS) on a human pancreatic specimen. Based on the measurement results, the margin of the malignant tumor has been successfully determined optically, which matches well with the histological results

Survival of pancreatic cancer cells lacking KRAS function

Activating mutations in the proto-oncogene KRAS are a hallmark of pancreatic ductal adenocarcinoma (PDAC), an aggressive malignancy with few effective therapeutic options. Despite efforts to develop KRAS-targeted drugs, the absolute dependence of PDAC cells on KRAS remains incompletely understood. Here we model complete KRAS inhibition using CRISPR/Cas-mediated genome editing and demonstrate that KRAS is dispensable in a subset of human and mouse PDAC cells. Remarkably, nearly all KRAS deficient cells exhibit phosphoinositide 3-kinase (PI3K)-dependent mitogen-activated protein kinase (MAPK) signaling and induced sensitivity to PI3K inhibitors. Furthermore, comparison of gene expression profiles of PDAC cells retaining or lacking KRAS reveal a role of KRAS in the suppression of metastasis-related genes. Collectively, these data underscore the potential for PDAC resistance to even the very best KRAS inhibitors and provide insights into mechanisms of response and resistance to KRAS inhibition

Comparison of Magnetic Resonance Feature Tracking for Strain Calculation With Harmonic Phase Imaging Analysis

ObjectivesTo compare a steady-state free precession cine sequence–based technique (feature tracking [FT]) to tagged harmonic phase (HARP) analysis for peak average circumferential myocardial strain (εcc) analysis in a large and heterogeneous population of boys with Duchenne muscular dystrophy (DMD).BackgroundCurrent εcc assessment techniques require cardiac magnetic resonance–tagged imaging sequences, and their analysis is complex. The FT method can readily be performed on standard cine (steady-state free precession) sequences.MethodsWe compared mid-left ventricular whole-slice εcc by the 2 techniques in 191 DMD patients grouped according to age and severity of cardiac dysfunction: group B: DMD patients 10 years and younger with normal ejection fraction (EF); group C: DMD patients older than 10 years with normal EF; group D: DMD patients older than 10 years with reduced EF but negative myocardial delayed enhancement (MDE); group E: DMD patients older than 10 years with reduced EF and positive MDE; and group A: 42 control subjects. Retrospective, offline analysis was performed on matched tagged and steady-state free precession slices.ResultsFor the entire study population (N = 233), mean FT εcc values (−13.3 ± 3.8%) were highly correlated with HARP εcc values (−13.6 ± 3.4%), with a Pearson correlation coefficient of 0.899. The mean εcc of DMD patients determined by HARP (−12.52 ± 2.69%) and FT (−12.16 ± 3.12%) was not significantly different (p = NS). Similarly, the mean εcc of the control subjects by determined HARP (−18.85 ± 1.86) and FT (−18.81 ± 1.83) was not significantly different (p = NS). Excellent correlation between the 2 methods was found among subgroups A through E, except there was no significant difference in strain between groups B and C with FT analysis.ConclusionsFT-based assessment of εcc correlates highly with εcc derived from tagged images in a large DMD patient population with a wide range of cardiac dysfunction and can be performed without additional imaging