Expressions 1986

https://openspace.dmacc.edu/expressions/1007/thumbnail.jp

ResBoost: characterizing and predicting catalytic residues in enzymes

Abstract Background Identifying the catalytic residues in enzymes can aid in understanding the molecular basis of an enzyme's function and has significant implications for designing new drugs, identifying genetic disorders, and engineering proteins with novel functions. Since experimentally determining catalytic sites is expensive, better computational methods for identifying catalytic residues are needed. Results We propose ResBoost, a new computational method to learn characteristics of catalytic residues. The method effectively selects and combines rules of thumb into a simple, easily interpretable logical expression that can be used for prediction. We formally define the rules of thumb that are often used to narrow the list of candidate residues, including residue evolutionary conservation, 3D clustering, solvent accessibility, and hydrophilicity. ResBoost builds on two methods from machine learning, the AdaBoost algorithm and Alternating Decision Trees, and provides precise control over the inherent trade-off between sensitivity and specificity. We evaluated ResBoost using cross-validation on a dataset of 100 enzymes from the hand-curated Catalytic Site Atlas (CSA). Conclusion ResBoost achieved 85% sensitivity for a 9.8% false positive rate and 73% sensitivity for a 5.7% false positive rate. ResBoost reduces the number of false positives by up to 56% compared to the use of evolutionary conservation scoring alone. We also illustrate the ability of ResBoost to identify recently validated catalytic residues not listed in the CSA

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/μL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count \u3c250 \u3e× 103/μL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/μL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring

Organizing risk: organization and management theory for the risk society

Risk has become a crucial part of organizing, affecting a wide range of organizations in all sectors. We identify, review and integrate diverse literatures relevant to organizing risk, building on an existing framework that describes how risk is organized in three ‘modes’ – prospectively, in real-time, and retrospectively. We then identify three critical issues in the existing literature: its fragmented nature; its neglect of the tensions associated with each of the modes; and its tendency to assume that the meaning of an object in relation to risk is singular and stable. We provide a series of new insights with regard to each of these issues. First, we develop the concept of a risk cycle that shows how organizations engage with all three modes and transition between them over time. Second, we explain why the tensions have been largely ignored and show how studies using a risk work perspective can provide further insights into them. Third, we develop the concept of risk translation to highlight the ways in the meanings of risks can be transformed and to identify the political consequences of such translations. We conclude the paper with a research agenda to elaborate these insights and ideas further

Unexpected diversity in socially synchronized rhythms of shorebirds

The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators. Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring). The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood. Here we investigate these rhythms in the context of biparental care, a particularly sensitive phase of social synchronization where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within-and between-species diversity in incubation rhythms. Between species, the median length of one parent's incubation bout varied from 1-19 h, whereas period length-the time in which a parent's probability to incubate cycles once between its highest and lowest value-varied from 6-43 h. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or who actively protect their nest against predators. Rhythms entrainable to the 24-h light-dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity. The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.</p

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg 2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF’s public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope

The Zwicky Transient Facility: Science Objectives

The Zwicky Transient Facility (ZTF), a public–private enterprise, is a new time-domain survey employing a dedicated camera on the Palomar 48-inch Schmidt telescope with a 47 deg2 field of view and an 8 second readout time. It is well positioned in the development of time-domain astronomy, offering operations at 10% of the scale and style of the Large Synoptic Survey Telescope (LSST) with a single 1-m class survey telescope. The public surveys will cover the observable northern sky every three nights in g and r filters and the visible Galactic plane every night in g and r. Alerts generated by these surveys are sent in real time to brokers. A consortium of universities that provided funding (“partnership”) are undertaking several boutique surveys. The combination of these surveys producing one million alerts per night allows for exploration of transient and variable astrophysical phenomena brighter than r∼20.5 on timescales of minutes to years. We describe the primary science objectives driving ZTF, including the physics of supernovae and relativistic explosions, multi-messenger astrophysics, supernova cosmology, active galactic nuclei, and tidal disruption events, stellar variability, and solar system objects. © 2019. The Astronomical Society of the Pacific

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection