Thromboinflammatory changes in plasma proteome of pregnant women with PCOS detected by quantitative label-free proteomics

Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. Several adverse pregnancy outcomes and abnormalities of the placenta have been associated with PCOS. By using quantitative label-free proteomics we investigated whether changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. A total of 169 proteins with >= 2 unique peptides were detected to be differentially expressed between women with PCOS (n = 7) and matched controls (n = 20) at term of pregnancy, out of which 35 were significant (p-value <0.05). A pathway analysis revealed that networks related to humoral immune responses, inflammatory responses, cardiovascular disease and cellular growth and proliferation were affected by PCOS. Classification of cases and controls was carried out using principal component analysis, orthogonal projections on latent structure-discriminant analysis (OPLS-DA), hierarchical clustering, self-organising maps and ROC-curve analysis. The most significantly enriched proteins in PCOS were properdin and insulin-like growth factor II. In the dataset, properdin had the best predictive accuracy for PCOS (AUC=1). Additionally, properdin abundances correlated with AMH levels in pregnant women.Peer reviewe

On the minimum transport required to passively suppress runaway electrons in SPARC disruptions

In [V.A. Izzo et al 2022 Nucl. Fusion 62 096029], state-of-the-art modeling of thermal and current quench (CQ) MHD coupled with a self-consistent evolution of runaway electron (RE) generation and transport showed that a non-axisymmetric (n = 1) in-vessel coil could passively prevent RE beam formation during disruptions in SPARC, a compact high-field tokamak projected to achieve a fusion gain Q > 2 in DT plasmas. However, such suppression requires finite transport of REs within magnetic islands and re-healed flux surfaces; conservatively assuming zero transport in these regions leads to an upper bound of RE current ~1 MA compared to ~8.7 MA of pre-disruption plasma current. Further investigation finds that core-localized electrons, within r/a < 0.3 and with kinetic energies 0.2-15 MeV, contribute most to the RE plateau formation. Yet only a relatively small amount of transport, i.e. a diffusion coefficient ~18 $\mathrm{m^2/s}$, is needed in the core to fully mitigate these REs. Properly accounting for (i) the CQ electric field's effect on RE transport in islands and (ii) the contribution of significant RE currents to disruption MHD may help achieve this

What do European women know about their female cancer risks and cancer screening? A cross-sectional online intervention survey in five European countries

OBJECTIVES: Informed decisions about cancer screening require accurate knowledge regarding cancer risks and screening. This study investigates: (1) European women's knowledge of their risk of developing breast, ovarian, cervical or endometrial cancer, (2) their knowledge about mammography screening and (3) whether an evidence-based leaflet improves their knowledge. DESIGN: Cross-sectional online intervention survey. SETTING: National samples from five European countries (Czech Republic, Germany, UK, Italy and Sweden)-drawn from the Harris Interactive and the Toluna panel, respectively, in January 2017-were queried on their knowledge of age-specific risks of developing breast, cervical, ovarian or endometrial cancer within the next 10 years and of mammography screening before and after intervention. PARTICIPANTS: Of 3629 women (inclusion criteria: age 40-75 years) invited, 2092 responded and 1675 completed the survey (response rate: 61.4%). INTERVENTION: Evidence-based leaflet summarising information on age-adjusted female cancer risks, mammography and aspects of cancer prevention. PRIMARY OUTCOME MEASURES: Proportion of women (1) accurately estimating their risk of four female cancers, (2) holding correct assumptions of mammography screening and (3) changing their estimations and assumptions after exposure to leaflet. FINDINGS: Across countries, 59.2% (95% CI 56.8% to 61.6%) to 91.8% (95% CI 90.3% to 93.0%) overestimated their female cancer risks 7-33 fold (mediansacross tumours: 50.0 to 200.0). 26.5% (95% CI 24.4% to 28.7%) were aware that mammography screening has both benefits and harms. Women who accurately estimated their breast cancer risk were less likely to believe that mammography prevents cancer (p<0.001). After leaflet intervention, knowledge of cancer risks improved by 27.0 (95% CI 24.9 to 29.2) to 37.1 (95% CI 34.8 to 39.4) percentage points and of mammography by 23.0 (95% CI 21.0 to 25.1) percentage points. CONCLUSION: A considerable number of women in five European countries may not possess the prerequisites for an informed choice on cancer screening. Evidence-based information in patient leaflets can improve this situation

Acoustic characteristics of a ported shroud turbocompressor operating at design conditions

[EN] In this article, the acoustic characterisation of a turbocharger compressor with ported shroud design is carried out through the numerical simulation of the system operating under design conditions of maximum isentropic efficiency. While ported shroud compressors have been proposed as a way to control the flow near unstable conditions in order to obtain a more stable operation and enhance deep surge margin, it is often assumed that the behaviour under stable design conditions is characterised by a smooth, non-detached flow that matches an equivalent standard compressor. Furthermore, research is scarce regarding the acoustic effects of the ported shroud addition, especially under the design conditions. To analyse the flow field evolution and its relation with the noise generation, spectral signatures using statistical and scale-resolving turbulence modelling methods are obtained after successfully validating the performance and acoustic predictions of the numerical model with experimental measurements. Propagation of the frequency content through the ducts has been estimated with the aid of pressure decomposition methods to enhance the content coming from the compressor. Expected acoustic phenomena such as `buzz-saw¿ tones, blade passing peaks and broadband noise are correctly identified in the modelled spectrum. Analysis of the flow behaviour in the ported shroud shows rotating structures through the slot that may impact the acoustic and vibration response. Further inspection of the pressure field through modal decomposition confirms the influence of the ported shroud cavity in noise generation and propagation, especially at lower frequencies, suggesting that further research should be carried out on the impact these flow enhancement solutions have on the noise emission of the turbocharger.The project was sponsored and supported by BorgWarner Turbo Systems and the Regional Growth Fund (RGF Grant Award 01.09.07.01/1789C). The authors would like to thank BorgWarner Turbo Systems for permission to publish the results presented in this article. The support of the HPC group at the University of Huddersfield is gratefully acknowledged.Sharma, S.; Broatch, A.; Garcia Tiscar, J.; Allport, JM.; Nickson, AK. (2020). Acoustic characteristics of a ported shroud turbocompressor operating at design conditions. International Journal of Engine Research. 21(8):1454-1468. https://doi.org/10.1177/1468087418814635S14541468218Sundström, E., Semlitsch, B., & Mihăescu, M. (2017). Generation Mechanisms of Rotating Stall and Surge in Centrifugal Compressors. Flow, Turbulence and Combustion, 100(3), 705-719. doi:10.1007/s10494-017-9877-zGonzalez, A., Ferrer, M., de Diego, M., Piñero, G., & Garcia-Bonito, J. . (2003). Sound quality of low-frequency and car engine noises after active noise control. Journal of Sound and Vibration, 265(3), 663-679. doi:10.1016/s0022-460x(02)01462-1Brizon, C. J. da S., & Bauzer Medeiros, E. (2012). Combining subjective and objective assessments to improve acoustic comfort evaluation of motor cars. Applied Acoustics, 73(9), 913-920. doi:10.1016/j.apacoust.2012.03.013Teng, C., & Homco, S. (2009). Investigation of Compressor Whoosh Noise in Automotive Turbochargers. SAE International Journal of Passenger Cars - Mechanical Systems, 2(1), 1345-1351. doi:10.4271/2009-01-2053Figurella, N., Dehner, R., Selamet, A., Tallio, K., Miazgowicz, K., & Wade, R. (2014). Noise at the mid to high flow range of a turbocharger compressor. Noise Control Engineering Journal, 62(5), 306-312. doi:10.3397/1/376229Torregrosa, A. J., Broatch, A., Margot, X., García-Tíscar, J., Narvekar, Y., & Cheung, R. (2017). Local flow measurements in a turbocharger compressor inlet. Experimental Thermal and Fluid Science, 88, 542-553. doi:10.1016/j.expthermflusci.2017.07.007Broatch, A., Galindo, J., Navarro, R., García-Tíscar, J., Daglish, A., & Sharma, R. K. (2015). Simulations and measurements of automotive turbocharger compressor whoosh noise. Engineering Applications of Computational Fluid Mechanics, 9(1), 12-20. doi:10.1080/19942060.2015.1004788Raitor, T., & Neise, W. (2008). Sound generation in centrifugal compressors. Journal of Sound and Vibration, 314(3-5), 738-756. doi:10.1016/j.jsv.2008.01.034Galindo, J., Tiseira, A., Navarro, R., & López, M. A. (2015). Influence of tip clearance on flow behavior and noise generation of centrifugal compressors in near-surge conditions. International Journal of Heat and Fluid Flow, 52, 129-139. doi:10.1016/j.ijheatfluidflow.2014.12.004Broatch, A., Galindo, J., Navarro, R., & García-Tíscar, J. (2014). Methodology for experimental validation of a CFD model for predicting noise generation in centrifugal compressors. International Journal of Heat and Fluid Flow, 50, 134-144. doi:10.1016/j.ijheatfluidflow.2014.06.006Semlitsch, B., & Mihăescu, M. (2016). Flow phenomena leading to surge in a centrifugal compressor. Energy, 103, 572-587. doi:10.1016/j.energy.2016.03.032Sundström, E., Semlitsch, B., & Mihăescu, M. (2018). Acoustic signature of flow instabilities in radial compressors. Journal of Sound and Vibration, 434, 221-236. doi:10.1016/j.jsv.2018.07.040Torregrosa, A. J., Broatch, A., Margot, X., & García-Tíscar, J. (2016). Experimental methodology for turbocompressor in-duct noise evaluation based on beamforming wave decomposition. Journal of Sound and Vibration, 376, 60-71. doi:10.1016/j.jsv.2016.04.035Nicoud, F., & Ducros, F. (1999). Flow, Turbulence and Combustion, 62(3), 183-200. doi:10.1023/a:1009995426001Chow, P., Cross, M., & Pericleous, K. (1996). A natural extension of the conventional finite volume method into polygonal unstructured meshes for CFD application. Applied Mathematical Modelling, 20(2), 170-183. doi:10.1016/0307-904x(95)00156-eKaji, S., & Okazaki, T. (1970). Generation of sound by rotor-stator interaction. Journal of Sound and Vibration, 13(3), 281-307. doi:10.1016/s0022-460x(70)80020-7Sivagnanasundaram, S., Spence, S., & Early, J. (2013). Map Width Enhancement Technique for a Turbocharger Compressor. Journal of Turbomachinery, 136(6). doi:10.1115/1.4007895Aubry, N. (1991). On the hidden beauty of the proper orthogonal decomposition. Theoretical and Computational Fluid Dynamics, 2(5-6), 339-352. doi:10.1007/bf00271473Wold, S., Esbensen, K., & Geladi, P. (1987). Principal component analysis. Chemometrics and Intelligent Laboratory Systems, 2(1-3), 37-52. doi:10.1016/0169-7439(87)80084-9LIANG, Y. C., LEE, H. P., LIM, S. P., LIN, W. Z., LEE, K. H., & WU, C. G. (2002). PROPER ORTHOGONAL DECOMPOSITION AND ITS APPLICATIONS—PART I: THEORY. Journal of Sound and Vibration, 252(3), 527-544. doi:10.1006/jsvi.2001.4041Abdi, H., & Williams, L. J. (2010). Principal component analysis. Wiley Interdisciplinary Reviews: Computational Statistics, 2(4), 433-459. doi:10.1002/wics.101Nikiforov, V. (2007). The energy of graphs and matrices. Journal of Mathematical Analysis and Applications, 326(2), 1472-1475. doi:10.1016/j.jmaa.2006.03.07

Excitons in a Photosynthetic Light-Harvesting System: A Combined Molecular Dynamics/Quantum Chemistry and Polaron Model Study

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with a novel approach which combines molecular dynamics (MD) simulations with quantum chemistry (QC) calculations. The MD simulations of an LH-II complex, solvated and embedded in a lipid bilayer at physiological conditions (with total system size of 87,055 atoms) revealed a pathway of a water molecule into the B800 binding site, as well as increased dimerization within the B850 BChl ring, as compared to the dimerization found for the crystal structure. The fluctuations of pigment (B850 BChl) excitation energies, as a function of time, were determined via ab initio QC calculations based on the geometries that emerged from the MD simulations. From the results of these calculations we constructed a time-dependent Hamiltonian of the B850 exciton system from which we determined the linear absorption spectrum. Finally, a polaron model is introduced to describe quantum mechanically both the excitonic and vibrational (phonon) degrees of freedom. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function are derived from the MD/QC simulations. It is demonstrated that, in the framework of the polaron model, the absorption spectrum of the B850 excitons can be calculated from the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined MD/QC simulations. The obtained result is in good agreement with the experimentally measured absorption spectrum.Comment: REVTeX3.1, 23 pages, 13 (EPS) figures included. A high quality PDF file of the paper is available at http://www.ks.uiuc.edu/Publications/Papers/PDF/DAMJ2001/DAMJ2001.pd

Plasma Dynamics

Contains reports on three research projects.National Science Foundation under Grant G-9330Air Force Cambridge Research Center under Contract AF-19(604)-5992United States Air Force (WADD Contract AF33(616)-3984)Contract AF19(604)-4551 with Air Force Cambridge Research CenterAeronautical Accessories Laboratory, Wright Air Development Division, Wright-Patterson Air Force Base, Ohio (Air Force Contract AF33(616)-3984, Project 8149, Task No. 61098)Atomic Energy Commission under Contract AT(30-1)-184

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Manipulating charge transfer excited state relaxation and spin crossover in iron coordination complexes with ligand substitution

Developing light-harvesting and photocatalytic molecules made with iron could provide a cost effective, scalable, and environmentally benign path for solar energy conversion. To date these developments have been limited by the sub-picosecond metal-to-ligand charge transfer (MLCT) electronic excited state lifetime of iron based complexes due to spin crossover-the extremely fast intersystem crossing and internal conversion to high spin metal-centered excited states. We revitalize a 30 year old synthetic strategy for extending the MLCT excited state lifetimes of iron complexes by making mixed ligand iron complexes with four cyanide (CN-;) ligands and one 2,2′-bipyridine (bpy) ligand. This enables MLCT excited state and metal-centered excited state energies to be manipulated with partial independence and provides a path to suppressing spin crossover. We have combined X-ray Free-Electron Laser (XFEL) Kβ hard X-ray fluorescence spectroscopy with femtosecond time-resolved UV-visible absorption spectroscopy to characterize the electronic excited state dynamics initiated by MLCT excitation of [Fe(CN)4(bpy)]2-. The two experimental techniques are highly complementary; the time-resolved UV-visible measurement probes allowed electronic transitions between valence states making it sensitive to ligand-centered electronic states such as MLCT states, whereas the Kβ fluorescence spectroscopy provides a sensitive measure of changes in the Fe spin state characteristic of metal-centered excited states. We conclude that the MLCT excited state of [Fe(CN)4(bpy)]2- decays with roughly a 20 ps lifetime without undergoing spin crossover, exceeding the MLCT excited state lifetime of [Fe(2,2′-bipyridine)3]2+ by more than two orders of magnitude

Standing genetic variation and compensatory evolution in transgenic organisms: a growth-enhanced salmon simulation

Genetically modified strains usually are generated within defined genetic backgrounds to minimize variation for the engineered characteristic in order to facilitate basic research investigations or for commercial application. However, interactions between transgenes and genetic background have been documented in both model and commercial agricultural species, indicating that allelic variation at transgene-modifying loci are not uncommon in genomes. Engineered organisms that have the potential to allow entry of transgenes into natural populations may cause changes to ecosystems via the interaction of their specific phenotypes with ecosystem components and services. A transgene introgressing through natural populations is likely to encounter a range of natural genetic variation (among individuals or sub-populations) that could result in changes in phenotype, concomitant with effects on fitness and ecosystem consequences that differ from that seen in the progenitor transgenic strain. In the present study, using a growth hormone transgenic salmon example, we have modeled selection of modifier loci (single and multiple) in the presence of a transgene and have found that accounting for genetic background can significantly affect the persistence of transgenes in populations, potentially reducing or reversing a “Trojan gene” effect. Influences from altered life history characteristics (e.g., developmental timing, age of maturation) and compensatory demographic/ecosystem controls (e.g., density dependence) also were found to have a strong influence on transgene effects. Further, with the presence of a transgene in a population, genetic backgrounds were found to shift in non-transgenic individuals as well, an effect expected to direct phenotypes away from naturally selected optima. The present model has revealed the importance of understanding effects of selection for background genetics on the evolution of phenotypes in populations harbouring transgenes

Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV

Aim: This thesis aims to provide a multidimensional assessment of infection risks and to evaluate strategies for HPV prevention including vaccination with quadrivalent HPVvaccines, dose-level vaccine effectiveness and condom use in high STI risk situations. Methods: Multiple population-based registers and questionnaire responses provided data for this thesis. Various multivariable and univariate regression models were fit. Findings: Overall, quadrivalent HPV-vaccination was highly effective against genital warts (GW) also referred to as condyloma, which is the first HPV disease endpoint possible to measure. However, effectiveness was contingent upon young age-at-first vaccination, with effectiveness declining steadily the older the age-at-first vaccination. Among women above 20 years of age there was low to immeasurable effectiveness and suggestive evidence vaccinations in this age group tended to reach women at high GW risk. There were marked socioeconomic disparities in the opportunistic (on-demand with co-pay) vaccination strategy evaluated, with women and girls who have parents with the highest education level compared to the lowest having a 15 times greater likelihood to be vaccinated (Study III). Once vaccination was initiated, however, high parental education level was unrelated to vaccination completion. Maximum protection against GW was found among girls vaccinated under the age of 17 who had received three doses of the vaccine. No differences in effectiveness were found for girls who received twodoses between ages 10-16 with that of those who received three-doses between ages 17- 19 (Study IV). GW affects more men than women in Sweden as of 2010 with 453 per 100 000 men and 365 per 100 000 women treated. A decline between 25-30% was seen between 2006 and 2010 among women in the age groups with the highest vaccination coverage. No decline was found amongst men and their GW incidence has steadily increased between 2006 and 2010 (Study II). Reported condom use in high risk situations was low among both men and women, with 41% of men and 34% of women reporting always/almost always condom use with temporary partners. STI risk perception was also low, with approximately 10% of sexually active respondents considering themselves at large risk of contracting an STI. There was no association between men’s condom use and their STI risk perception but there was an association for women (Study I). Conclusions: Results suggest that males bear a substantial burden of HPV-related condyloma where incidence has dropped among women. When planning HPVvaccination among females, efforts should target girls under age 14 for maximum effectiveness. Quadrivalent HPV-vaccination offers most protection against condyloma at three doses. Gross social inequity was found with opportunistic HPV-vaccination. There were large gender differences in factors associated with condom use in high risk situations and STI risk perceptions