Molecular dynamics simulations of the growth of poly(chloro-para-xylylene) films

Parylene C, poly(chloro-para-xylylene) is the most widely used member of the parylene family due to its excellent chemical and physical properties. In this work we analyzed the formation of the parylene C film using molecular mechanics and molecular dynamics methods. A five unit chain is necessary to create a stable hydrophobic cluster and to adhere to a covered surface. Two scenarios were deemed to take place. The obtained results are consistent with a polymer film scaling growth mechanism and contribute to the description of the dynamic growth of the parylene C polymer

On the origin of the Boson peak in globular proteins

We study the Boson Peak phenomenology experimentally observed in globular proteins by means of elastic network models. These models are suitable for an analytic treatment in the framework of Euclidean Random Matrix theory, whose predictions can be numerically tested on real proteins structures. We find that the emergence of the Boson Peak is strictly related to an intrinsic mechanical instability of the protein, in close similarity to what is thought to happen in glasses. The biological implications of this conclusion are also discussed by focusing on a representative case study.Comment: Proceedings of the X International Workshop on Disordered Systems, Molveno (2006

How to create an operational multi-model of seasonal forecasts?

Seasonal forecasts of variables like near-surface temperature or precipitation are becoming increasingly important for a wide range of stakeholders. Due to the many possibilities of recalibrating, combining, and verifying ensemble forecasts, there are ambiguities of which methods are most suitable. To address this we compare approaches how to process and verify multi-model seasonal forecasts based on a scientific assessment performed within the framework of the EU Copernicus Climate Change Service (C3S) Quality Assurance for Multi-model Seasonal Forecast Products (QA4Seas) contract C3S 51 lot 3. Our results underpin the importance of processing raw ensemble forecasts differently depending on the final forecast product needed. While ensemble forecasts benefit a lot from bias correction using climate conserving recalibration, this is not the case for the intrinsically bias adjusted multi-category probability forecasts. The same applies for multi-model combination. In this paper, we apply simple, but effective, approaches for multi-model combination of both forecast formats. Further, based on existing literature we recommend to use proper scoring rules like a sample version of the continuous ranked probability score and the ranked probability score for the verification of ensemble forecasts and multi-category probability forecasts, respectively. For a detailed global visualization of calibration as well as bias and dispersion errors, using the Chi-square decomposition of rank histograms proved to be appropriate for the analysis performed within QA4Seas.The research leading to these results is part of the Copernicus Climate Change Service (C3S) (Framework Agreement number C3S_51_Lot3_BSC), a program being implemented by the European Centre for Medium-Range Weather Forecasts (ECMWF) on behalf of the European Commission. Francisco Doblas-Reyes acknowledges the support by the H2020 EUCP project (GA 776613) and the MINECO-funded CLINSA project (CGL2017-85791-R)

ParaVR: A Virtual Reality Training Simulator for Paramedic Skills maintenance

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Paramedic Practice, copyright © MA Healthcare, after peer review and technical editing by the publisher. To access the final edited and published work see https://www.paramedicpractice.com/features/article/paravr-a-virtual-reality-training-simulator-for-paramedic-skills-maintenance.Background, Virtual Reality (VR) technology is emerging as a powerful educational tool which is used in medical training and has potential benefits for paramedic practice education. Aim The aim of this paper is to report development of ParaVR, which utilises VR to address skills maintenance for paramedics. Methods Computer scientists at the University of Chester and the Welsh Ambulance Services NHS Trust (WAST) developed ParaVR in four stages: 1. Identifying requirements and specifications 2. Alpha version development, 3. Beta version development 4. Management: Development of software, further funding and commercialisation. Results Needle Cricothyrotomy and Needle Thoracostomy emerged as candidates for the prototype ParaVR. The Oculus Rift head mounted display (HMD) combined with Novint Falcon haptic device was used, and a virtual environment crafted using 3D modelling software, ported (a computing term meaning transfer (software) from one system or machine to another) onto Oculus Go and Google cardboard VR platform. Conclusion VR is an emerging educational tool with the potential to enhance paramedic skills development and maintenance. The ParaVR program is the first step in our development, testing, and scaling up of this technology

Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins

A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed

Using Entropy Maximization to Understand the Determinants of Structural Dynamics beyond Native Contact Topology

Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria

Reconciling the stratigraphy and depositional history of the Lycian orogen-top basins, SW Anatolia

Terrestrial fossil records from the SWAnatolian basins are crucial both for regional correlations and palaeoenvironmental reconstructions. By reassessing biostratigraphic constraints and incorporating new fossil data, we calibrated and reconstructed the late Neogene andQuaternary palaeoenvironments within a regional palaeogeographical framework. The culmination of the Taurides inSWAnatolia was followed by a regional crustal extension from the late Tortonian onwards that created a broad array of NE-trending orogen-top basins with synchronic associations of alluvial fan, fluvial and lacustrine deposits. The terrestrial basins are superimposed on the upper Burdigalian marine units with a c. 7 myr of hiatus that corresponds to a shift from regional shortening to extension. The initial infill of these basins is documented by a transition from marginal alluvial fans and axial fluvial systems into central shallow-perennial lakes coinciding with a climatic shift from warm/humid to arid conditions. The basal alluvial fan deposits abound in fossil macro-mammals of an early Turolian (MN11–12; late Tortonian) age. The Pliocene epoch in the region was punctuated by subhumid/humid conditions resulting in a rise of local base levels and expansion of lakes as evidenced by marsh-swamp deposits containing diverse fossilmammal assemblages indicating late Ruscinian (lateMN15; late Zanclean) ageWe are grateful for the support of the international bilateral project between The Scientific and Technological Research Council of Turkey (TUBITAK) and The Russian Scientific Foundation (RFBR) with grant a number of 111Y192. M.C.A. is grateful to the Turkish Academy of Sciences (TUBA) for a GEBIP (Young Scientist Award) grant. T.K. and S.M. are grateful to the Ege University Scientific Research Center for the TTM/002/2016 and TTM/001/2016 projects. M.C.A., H.A., S.M. and M.B. have obtained Martin and Temmick Fellowships at Naturalis Biodiversity Center (Leiden). F.A.D. is supported by a Mehmet Akif Ersoy University Scientific Research Grant. T.A.N. is supported by an Alexander-von-Humboldt Scholarship. L.H.O. received support from TUBITAK under the 2221 program for visiting scientists

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention