Application of the Optimized Baxter Model to the hard-core attractive Yukawa system

We perform Monte Carlo simulations on the hard-core attractive Yukawa system to test the Optimized Baxter Model that was introduced in [P.Prinsen and T. Odijk, J. Chem. Phys. 121, p.6525 (2004)] to study a fluid phase of spherical particles interacting through a short-range pair potential. We compare the chemical potentials and pressures from the simulations with analytical predictions from the Optimized Baxter Model. We show that the model is accurate to within 10 percent over a range of volume fractions from 0.1 to 0.4, interaction strengths up to three times the thermal energy and interaction ranges from 6 to 20 % of the particle diameter, and performs even better in most cases. We furthermore establish the consistency of the model by showing that the thermodynamic properties of the Yukawa fluid computed via simulations may be understood on the basis of one similarity variable, the stickiness parameter defined within the Optimized Baxter Model. Finally we show that the Optimized Baxter Model works significantly better than an often used, naive method determining the stickiness parameter by equating the respective second virial coefficients based on the attractive Yukawa and Baxter potentials.Comment: 11 pages, 8 figure

An experimental investigation and evaluation of a Doppler radar technique for the measurement of the flow generated by wing tip vortices Final summary report

Doppler radar measurements of flow generated by wing tip vortices using reflective chaff dispensed into vortice

Systematic review and meta-analysis of measurement properties of the Hip disability and Osteoarthritis Outcome Score - Physical Function Shortform (HOOS-PS) and the Knee Injury and Osteoarthritis Outcome Score - Physical Function Shortform (KOOS-PS)

Objective: The aim of this systematic review and meta-analysis was to evaluate all evidence on measurement properties of the Hip disability and Osteoarthritis Outcome Score - Physical function Shortform (HOOS-PS) and the Knee Injury and Osteoarthritis Outcome Score - Physical function Shortform (KOOS-PS). Design: This study was conducted according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews of PROMs. MEDLINE, EMBASE, The Cochrane Library, CINAHL and PsychINFO through February 2019 were searched. Eligible studies evaluated patients with hip or knee complaints and described a measurement property, interpretability, feasibility, or the development of either the HOOS-PS or KOOS-PS. Results: Twenty-three studies were included. For both questionnaires, the content validity was found inconsistent and the quality evidence was moderate for a sufficient reliability and high for an insufficient construct validity. The HOOS-PS had a high quality evidence of sufficient structural validity and internal consistency (pooled Cronbach's alpha 0.80; n = 3761) and low quality evidence of sufficient measurement error and indeterminate responsiveness. Concerning the KOOS-PS, the quality evidence was high for an insufficient responsiveness, moderate for an inconsistent structural validity and internal consistency and low for an inconsistent measurement error. Conclusions: The inconsistent evidence for content validity implies that scores on the HOOS-PS and KOOS-PS may inadequately reflect physical functioning. Furthermore, there is evidence for insufficient construct validity and responsiveness in patients with knee osteoarthritis receiving conservative treatment. Using the HOOS-PS or KOOS-PS as outcome measurement instruments for comparing outcomes, measuring improvements or benchmarking in patients with hip or knee complaints or undergoing arthroplasty should only be done with great caution. Review registration: PROSPERO number CRD4201706953

Fluid-crystal coexistence for proteins and inorganic nanocolloids: dependence on ionic strength

We investigate theoretically the fluid-crystal coexistence of solutions of globular charged nanoparticles like proteins and inorganic colloids. The thermodynamic properties of the fluid phase are computed via the optimized Baxter model. This is done specifically for lysozyme and silicotungstates for which the bare adhesion parameters are evaluated via the experimental second virial coefficients. The electrostatic free energy of the crystal is approximated by supposing the cavities in the interstitial phase between the particles are spherical in form. In the salt-free case a Poisson-Boltzmann equation is solved to calculate the effective charge on a particle and a Donnan approximation is used to derive the chemical potential and osmotic pressure in the presence of salt. The coexistence data of lysozyme and silicotungstates are analyzed within this scheme, especially with regard to the ionic-strength dependence of the chemical potentials. The latter agree within the two phases provided some upward adjustment of the effective charge is allowed for.Comment: 15 pages, 9 figure

Measurement properties of patient-reported outcome measures (PROMs) for women with Genitourinary Syndrome of Menopause: a systematic review

Background: Genitourinary Syndrome of Menopause (GSM) is a chronic and usually progressive skin disease which affects up to 50% of postmenopausal women. Symptoms, such as vaginal dryness, itching and burning have negative impacts on the women's sexual activity and often come along with urinary problems. Furthermore, these consequences influence the women's quality of life (QoL). Patient‐reported outcome measures can be used to measure the impact of GSM. Objectives: We aimed to identify all existing PROMs that were developed and/or validated for measuring patient‐reported outcomes in women with GSM or vulvovaginal symptoms during menopause and assess the quality of these PROMs in a transparent and structured way. Methods: We performed a systematic literature search in MEDLINE, EMBASE, Web of Science and smaller data bases, and hand‐searched reference lists of included studies. Only studies in English, German, French or Italian aiming at the evaluation of measurement properties, the development of a PROM, or the evaluation of the interpretability of the PROMs of interest were eligible. The methodological quality of eligible studies was evaluated with the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Quality criteria for good measurement properties were applied and the quality of evidence was graded using a GRADE approach. Information on interpretability and feasibility was extracted as well. PROMs were then categorized into three categories. PROMs of category A had evidence for sufficient content validity and at least low quality evidence for sufficient internal consistency, PROMs of category C had high‐quality evidence for an insufficient measurement property, and PROMs of category B could not be categorized in A or C. Results: Eight studies, two of which were found by reference list screening, were included. These studies reported on four PROMs. All of the included PROMs showed sufficient content validity. Two of the PROMs, the Vaginal Symptoms Questionnaire (VSQ) and the Day‐to‐Day Impact of Vaginal Aging (DIVA) showed moderate‐to‐high quality of evidence for sufficient structural validity and internal consistency, and were categorized as A. They can be therefore recommended for future use. The UGAQoL still has the opportunity to be recommended for use, but further validation is needed. The overall rating was often indeterminate since structural validity or important reliability parameters were not reported. The Urogenital symptom scale cannot be recommended for use since there was high quality of evidence for insufficient structural validity and internal consistency. Conclusion: Currently, two PROMs for women with GSM or vulvovaginal symptoms can be recommended. Nevertheless, those PROMs do not cover the urinary component of GSM. Future validation research should try to confirm and extend the measurement properties of those PROMs to strengthen this recommendation. PROSPERO registration CRD42018092384

Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein engineering

Although the Plasmodium falciparum hexose transporter PfHT has emerged as a promising target for anti-malarial therapy, previously identified small-molecule inhibitors have lacked promising drug-like structural features necessary for development as clinical therapeutics. Taking advantage of emerging insight into structure/function relationships in homologous facilitative hexose transporters and our novel high throughput screening platform, we investigated the ability of compounds satisfying Lipinksi rules for drug likeness to directly interact and inhibit PfHT. The Maybridge HitFinder chemical library was interrogated by searching for compounds that reduce intracellular glucose by >40% at 10 μM. Testing of initial hits via measurement of 2-deoxyglucose (2-DG) uptake in PfHT over-expressing cell lines identified 6 structurally unique glucose transport inhibitors. WU-1 (3-(2,6-dichlorophenyl)-5-methyl-N-[2-(4-methylbenzenesulfonyl)ethyl]-1,2-oxazole-4-carboxamide) blocked 2-DG uptake (IC50 = 5.8 ± 0.6 μM) with minimal effect on the human orthologue class I (GLUTs 1–4), class II (GLUT8) and class III (GLUT5) facilitative glucose transporters. WU-1 showed comparable potency in blocking 2-DG uptake in freed parasites and inhibiting parasite growth, with an IC50 of 6.1 ± 0.8 μM and EC50 of 5.5 ± 0.6 μM, respectively. WU-1 also directly competed for N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) binding and inhibited the transport of D-glucose with an IC50 of 5.9 ± 0.8 μM in liposomes containing purified PfHT. Kinetic analysis revealed that WU-1 acts as a non-competitive inhibitor of zero-trans D-fructose uptake. Decreased potency for WU-1 and the known endofacial ligand cytochalasin B was observed when PfHT was engineered to contain an N-terminal FLAG tag. This modification resulted in a concomitant increase in affinity for 4,6-O-ethylidene-α-D-glucose, an exofacially directed transport antagonist, but did not alter the Km for 2-DG. Taken together, these data are consistent with a model in which WU-1 binds preferentially to the transporter in an inward open conformation and support the feasibility of developing potent and selective PfHT antagonists as a novel class of anti-malarial drugs.</div