Network theory approach for data evaluation in the dynamic force spectroscopy of biomolecular interactions

Investigations of molecular bonds between single molecules and molecular complexes by the dynamic force spectroscopy are subject to large fluctuations at nanoscale and possible other aspecific binding, which mask the experimental output. Big efforts are devoted to develop methods for effective selection of the relevant experimental data, before taking the quantitative analysis of bond parameters. Here we present a methodology which is based on the application of graph theory. The force-distance curves corresponding to repeated pulling events are mapped onto their correlation network (mathematical graph). On these graphs the groups of similar curves appear as topological modules, which are identified using the spectral analysis of graphs. We demonstrate the approach by analyzing a large ensemble of the force-distance curves measured on: ssDNA-ssDNA, peptide-RNA (system from HIV1), and peptide-Au surface. Within our data sets the methodology systematically separates subgroups of curves which are related to different intermolecular interactions and to spatial arrangements in which the molecules are brought together and/or pulling speeds. This demonstrates the sensitivity of the method to the spatial degrees of freedom, suggesting potential applications in the case of large molecular complexes and situations with multiple binding sites

Monitoring core temperature of firefighters to validate a wearable non-invasive core thermometer in different types of protective clothing:Concurrent in-vivo validation

This study aims (1) to test the validity of a new non-invasive core thermometer, Cosinuss°, in rest and (2) during firefighting simulation tasks, against invasive temperature pill and inner-ear temperature and (3) to compare the change in core temperature of firefighters when working in two types of protective clothing (traditional turnout gear versus new concept). 11 active firefighters performed twice a selection of tasks during their periodic preventive medical examination and a fire-extinguishing task. Without correction no correlation between the Cosinuss° and thermometer pill (ICC≤0.09, p ≥ 0.154, LoA≥1.37) and a moderate correlation between Cosinuss° and inner-ear infrared (ICC = 0.40, p = 0.044, LoA±1.20) was observed. With individual correction both correlations were excellent (ICC≥0.84, p = 0.000, LoA≤0.30). However, during and after working all correlations were poor and non-significant (ICC≤0.38, p ≥ 0.091, LoA≥1.71). During firefighting tasks, the Cosinuss° is invalid for measuring the core temperature. No differences in heat development in the two types of protective clothing was proven

Reducing Inappropriate Proton Pump Inhibitors Use for Stress Ulcer Prophylaxis in Hospitalized Patients:Systematic Review of De-Implementation Studies

Background: A large proportion of proton pump inhibitor (PPI) prescriptions, including those for stress ulcer prophylaxis (SUP), are inappropriate. Our study purpose was to systematically review the effectiveness of de-implementation strategies aimed at reducing inappropriate PPI use for SUP in hospitalized, non-intensive care unit (non-ICU) patients. Methods: We searched MEDLINE and Embase databases (from inception to January 2020). Two authors independently screened references, performed data extraction, and critical appraisal. Randomized trials and comparative observational studies were eligible for inclusion. Criteria developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group were used for critical appraisal. Besides the primary outcome (inappropriate PPI prescription or use), secondary outcomes included (adverse) pharmaceutical effects and healthcare use. Results: We included ten studies in this review. Most de-implementation strategies contained an educational component (meetings and/or materials), combined with either clinical guideline implementation (n = 5), audit feedback (n = 3), organizational culture (n = 4), or reminders (n = 1). One study evaluating the de-implementation strategy effectiveness showed a significant reduction (RR 0.14; 95% CI 0.03–0.55) of new inappropriate PPI prescriptions. Out of five studies evaluating the effectiveness of de-implementing inappropriate PPI use, four found a significant reduction (RR 0.21; 95% CI 0.18–0.26 to RR 0.76; 95% CI 0.68–0.86). No significant differences in the occurrence of pharmaceutical effects (n = 1) and in length of stay (n = 3) were observed. Adverse pharmaceutical effects were reported in two studies and five studies reported on PPI or total drug costs. No pooled effect estimates were calculated because of large statistical heterogeneity between studies. Discussion: All identified studies reported mainly educational interventions in combination with one or multiple other intervention strategies and all interventions were targeted at providers. Most studies found a small to moderate reduction of (inappropriate) PPI prescriptions or use

Observational Validation of The Compensating Mass Flux Through The Shell Around Cumulus Clouds

The existence of a subsiding shell around cumulus clouds has been observed before in several aircraft measurement campaigns. Recent results from large-eddy simulations (LES) showed that the downward mass flux through the shell compensates for a significant fraction of the upward mass flux through the cloud. In this study, aeroplane measurements from the Rain In Cumulus over the Ocean (RICO) field campaign are used to verify the existence of this compensating mass flux. Just as in the LES results, the in-shell downward mass flux is found to be significant. However, a few differences were found in comparison with the LES results; most of them were explained by taking into account the difference between the two-dimensional slabs in LES and the one-dimensional lines from aeroplane observations

Formulation of the Dutch Atmospheric Large-Eddy Simulation (DALES) and Overview of Its Applications

The current version of the Dutch Atmospheric Large-Eddy Simulation (DALES) is presented. DALES is a large-eddy simulation code designed for studies of the physics of the atmospheric boundary layer, including convective and stable boundary layers as well as cloudy boundary layers. In addition, DALES can be used for studies of more specific cases, such as flow over sloping or heterogeneous terrain, and dispersion of inert and chemically active species. This paper contains an extensive description of the physical and numerical formulation of the code, and gives an overview of its applications and accomplishments in recent years

Functional analysis of the SRV-1 RNA frameshifting pseudoknot

Simian retrovirus type-1 uses programmed ribosomal frameshifting to control expression of the Gag-Pol polyprotein from overlapping gag and pol open-reading frames. The frameshifting signal consists of a heptanucleotide slippery sequence and a downstream-located 12-base pair pseudoknot. The solution structure of this pseudoknot, previously solved by NMR [Michiels,P.J., Versleijen,A.A., Verlaan,P.W., Pleij,C.W., Hilbers,C.W. and Heus,H.A. (2001) Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting. J. Mol. Biol., 310, 1109–1123] has a classical H-type fold and forms an extended triple helix by interactions between loop 2 and the minor groove of stem 1 involving base–base and base–sugar contacts. A mutational analysis was performed to test the functional importance of the triple helix for −1 frameshifting in vitro. Changing bases in L2 or base pairs in S1 involved in a base triple resulted in a 2- to 5-fold decrease in frameshifting efficiency. Alterations in the length of L2 had adverse effects on frameshifting. The in vitro effects were well reproduced in vivo, although the effect of enlarging L2 was more dramatic in vivo. The putative role of refolding kinetics of frameshifter pseudoknots is discussed. Overall, the data emphasize the role of the triple helix in −1 frameshifting

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients

Background &amp; aims: Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Methods: Using the experiences of seven cohort studies, which included healthy children and patients aged 2–22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. Results: From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated ‘user-friendly’, with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the ‘pediatric option’ for children aged &lt;6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. Conclusion: We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.</p