244 research outputs found
Where is the Wisdom We Have Lost in Technology?
Wisdom has been at the heart of practical, philosophical, and theological interest since antiquity but is now attracting interdisciplinary scientific interest from academic researchers in diverse disciplines. Practical wisdom is important from the IS perspective because we have built information tools and technologies that can harm or benefit us in various ways and it is important that we understand the implications of these technologies. The purpose of this panel is to start and stimulate conversations with the IS community on a broad array of individual, organizational and societal issues at the intersection of wisdom and technology. The hope is to take the first steps to bring together disparate notions on wisdom in an IS context and to explore new frameworks to advance research in this emerging area representing wisdom-based IS. Broadly, this panel will explore topics relating to extending knowledge management concepts for wisdom; making meaningful distinctions between knowledge, wisdom, ethics, and other related concepts in the context of information systems teaching, research, and practice; the design, management, use, and implications of technologies for consciously discovering, creating, sharing, and supporting wisdom in individuals, organizations, and societies; interdisciplinary or transdisciplinary understanding of the nature of wisdom in a technology-driven world; and mindful living with and connected by technologies for personal, professional, and societal well-being
Association of Cross-Reactive Antibodies Targeting Peptidyl-Arginine Deiminase 3 and 4 with Rheumatoid Arthritis-Associated Interstitial Lung Disease
Background:
A subset of rheumatoid arthritis (RA) patients have detectable antibodies directed against the peptidyl-arginine deiminase (PAD) enzyme isoforms 3 and 4. Anti-PAD3/4 cross-reactive antibodies (anti-PAD3/4XR) have been shown to lower the calcium threshold required for PAD4 activation, an effect potentially relevant to the pathogenesis of RA-associated interstitial lung disease (ILD).
Methods:
RA patients underwent multi-detector computed tomography (MDCT) of the chest with interpretation by a pulmonary radiologist for ILD features. A semi-quantitative ILD Score (range 0–32) was calculated. Concurrent serum samples were assessed for antibodies against PAD by immunoprecipitation with radiolabeled PAD3 and PAD4.
Results:
Among the 176 RA patients studied, any ILD was observed in 58 (33%) and anti-PAD3/4XR was detected in 19 (11%). The frequency of any ILD among those with anti-PAD3/4XR was 68% vs. 29% among those with no anti-PAD (crude OR = 5.39; p = 0.002) and vs. 27% among those with anti-PAD4 that was not cross-reactive with PAD3 (crude OR = 5.74; p = 0.001). Both associations were stronger after adjustment for relevant confounders (adjusted ORs = 7.22 and 6.61, respectively; both p-values<0.01). Among ever smokers with anti-PAD3/4XR, the adjusted frequency of any ILD was 93% vs. 17% for never smokers without the antibody (adjusted OR = 61.4; p = 0.001, p-value for the interaction of smoking with anti-PAD3/4XR<0.05).
Conclusions:
The prevalence and extent of ILD was markedly higher among RA patients with anti-PAD3/4 cross-reactive antibodies, even after accounting for relevant confounders, particularly among ever smokers. These findings may suggest etiopathologic mechanisms of RA-ILD, and their clinical utility for predicting ILD warrants additional study
Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis
A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls. Periodontitis was characterized by the presence of citrullinated autoantigens that are primary immune targets in RA. The citrullinome in periodontitis mirrored patterns of hypercitrullination observed in the rheumatoid joint, implicating this mucosal site in RA pathogenesis. Proteomic signatures of several microbial species were detected in hypercitrullinated periodontitis samples. Among these, Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils. We identified the pore-forming toxin leukotoxin-A (LtxA) as the molecular mechanism by which Aa triggers dysregulated activation of citrullinating enzymes in neutrophils, mimicking membranolytic pathways that sustain autoantigen citrullination in the RA joint. Moreover, LtxA induced changes in neutrophil morphology mimicking extracellular trap formation, thereby releasing the hypercitrullinated cargo. Exposure to leukotoxic Aa strains was confirmed in patients with RA and was associated with both anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). The effect of HLA-DRB1 shared epitope alleles on autoantibody positivity was limited to RA patients that were exposed to Aa. These studies identify the periodontal pathogen Aa as a candidate bacterial trigger of autoimmunity in RA
A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions
Eosinophilic esophagitis (EoE), a Th2-type allergic immune disorder characterized by an eosinophil-rich esophageal immune infiltrate, is often associated with food impaction (FI) in pediatric patients but the molecular mechanisms underlying the development of this complication are not well understood. We aim to identify molecular pathways involved in the development of FI. Due to large variations in disease presentation, our analysis was further geared to find markers capable of distinguishing EoE patients that are prone to develop food impactions and thus expand an established medical algorithm for EoE by developing a secondary analysis that allows for the identification of patients with food impactions as a distinct patient population. To this end, mRNA patterns from esophageal biopsies of pediatric EoE patients presenting with and without food impactions were compared and machine learning techniques were employed to establish a diagnostic probability score to identify patients with food impactions (EoE+FI). Our analysis showed that EoE patients with food impaction were indistinguishable from other EoE patients based on their tissue eosinophil count, serum IgE levels, or the mRNA transcriptome-based p(EoE). Irrespectively, an additional analysis loop of the medical algorithm was able to separate EoE+FI patients and a composite FI-score was established that identified such patients with a sensitivity of 93% and a specificity of 100%. The esophageal mRNA pattern of EoE+FI patients was typified by lower expression levels of mast cell markers and Th2 associated transcripts, such as FCERIB, CPA3, CCL2, IL4, and IL5. Furthermore, lower expression levels of regulators of esophageal motility (NOS2 and HIF1A) were detected in EoE+FI. The EoE+FI -specific mRNA pattern indicates that impaired motility may be one underlying factor for the development of food impactions in pediatric patients. The availability of improved diagnostic tools such as a medical algorithm for EoE subpopulations will have a direct impact on clinical practice because such strategies can identify molecular inflammatory characteristics of individual EoE patients, which, in turn, will facilitate the development of individualized therapeutic approaches that target the relevant pathways affected in each patient
The On-Site Analysis of the Cherenkov Telescope Array
The Cherenkov Telescope Array (CTA) observatory will be one of the largest
ground-based very high-energy gamma-ray observatories. The On-Site Analysis
will be the first CTA scientific analysis of data acquired from the array of
telescopes, in both northern and southern sites. The On-Site Analysis will have
two pipelines: the Level-A pipeline (also known as Real-Time Analysis, RTA) and
the level-B one. The RTA performs data quality monitoring and must be able to
issue automated alerts on variable and transient astrophysical sources within
30 seconds from the last acquired Cherenkov event that contributes to the
alert, with a sensitivity not worse than the one achieved by the final pipeline
by more than a factor of 3. The Level-B Analysis has a better sensitivity (not
be worse than the final one by a factor of 2) and the results should be
available within 10 hours from the acquisition of the data: for this reason
this analysis could be performed at the end of an observation or next morning.
The latency (in particular for the RTA) and the sensitivity requirements are
challenging because of the large data rate, a few GByte/s. The remote
connection to the CTA candidate site with a rather limited network bandwidth
makes the issue of the exported data size extremely critical and prevents any
kind of processing in real-time of the data outside the site of the telescopes.
For these reasons the analysis will be performed on-site with infrastructures
co-located with the telescopes, with limited electrical power availability and
with a reduced possibility of human intervention. This means, for example, that
the on-site hardware infrastructure should have low-power consumption. A
substantial effort towards the optimization of high-throughput computing
service is envisioned to provide hardware and software solutions with
high-throughput, low-power consumption at a low-cost.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
CRIMAC cruise report: Development of acoustic and optic methods for underwater target calssification - G.O. Sars 22.11 - 03.12 2022
The overarching objective of the survey is to collect data to support the CRIMAC activities and to collect data for the LoVe observatory. CRIMAC is a center of research-based innovation funded by the research council of Norway through their center for research-based innovation program (SFI). Sustainable, healthy food production and clean energy production for a growing population are important global goals, and CRIMAC will contribute to these by obtaining accurate underwater observations of gas, fish, nekton and other targets. The data will be used in conjunction with CRIMAC data from other surveys to build a reference data set for optical and acoustic target classification. The classification libraries will be used for developing methods and products toward the fishing industry and marine science. The survey was divided into two legs where leg one mainly focused on trawl instrumentation and data collection for behavioural studies on fish-trawl interactions. The main objectives of this part were to test in-trawl camera systems and data processing from such systems, test and develop trawl instrumentation and acoustic and optic monitoring of herring behaviour in relation to the trawl. The second leg of the survey focused mainly on broad band acoustic data, including sizing of fish using broad banded acoustics, noise estimation, calibration, time series consistency when changing to broad band acoustics, gas seep detection as well as performing the standard IMR LoVe transect.CRIMAC cruise report: Development of acoustic and optic methods for underwater target calssification - G.O. Sars 22.11 - 03.12 2022publishedVersio
Teaching Access, or Freedom of Information Law
Based on the author\u27s experience developing and administering the course and materials, this article provides an introduction and resources to teach a graduate journalism or professional law school course on access to government, commonly called freedom of information law , which may be constructed as a capstone course in law school. The appendices provide supporting material and references
Bacterial resistance to arsenic protects against protist killing
Protists kill their bacterial prey using toxic metals such as copper. Here we hypothesize that the metalloid arsenic has a similar role. To test this hypothesis, we examined intracellular survival of Escherichia coli (E. coli) in the amoeba Dictyostelium discoideum (D. discoideum). Deletion of the E. coli ars operon led to significantly lower intracellular survival compared to wild type E. coli. This suggests that protists use arsenic to poison bacterial cells in the phagosome, similar to their use of copper. In response to copper and arsenic poisoning by protists, there is selection for acquisition of arsenic and copper resistance genes in the bacterial prey to avoid killing. In agreement with this hypothesis, both copper and arsenic resistance determinants are widespread in many bacterial taxa and environments, and they are often found together on plasmids. A role for heavy metals and arsenic in the ancient predator–prey relationship between protists and bacteria could explain the widespread presence of metal resistance determinants in pristine environments
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