bluuebunny/crossref_metadata_2025_split huggingface dataset:
Essential genes shape cancer genomes through linear limitation of homozygous deletions
Authors: Pertesi Maroulio , Ekdahl Ludvig , Palm Angelica , Johnsson Ellinor , Järvstråt Linnea , Wihlborg Anna-Karin , Nilsson Björn 
Published: July 2019

AbstractThe landscape of somatic acquired deletions in cancer cells is shaped by positive and negative selection. Recurrent deletions typically target tumor suppressor, leading to positive selection. Simultaneously, loss of a nearby essential gene can lead to negative selection, and introduce latent vulnerabilities specific to cancer cells. Here we show that, under basic assumptions on positive and negative selection, deletion limitation gives rise to a statistical pattern where the frequency of homozygous deletions decreases approximately linearly between the deletion target gene and the nearest essential genes. Using DNA copy number data from 9,744 human cancer specimens, we demonstrate that linear deletion limitation exists and exposes deletion-limiting genes for seven known deletion targets (CDKN2A, RB1, PTEN, MAP2K4, NF1, SMAD4, and LINC00290). Downstream analysis of pooled CRISPR/Cas9 data provide further evidence of essentiality. Our results provide further insight into how the deletion landscape is shaped and identify potentially targetable vulnerabilities.
Positive functional synergy of structurally integrated artificial protein dimers assembled by Click chemistry
Authors: Worthy Harley L. , Auhim Husam Sabah , Jamieson W. David , Pope Jacob R. , Wall Aaron , Batchelor Robert , Johnson Rachel L. , Watkins Daniel W. , Rizkallah Pierre , Castell Oliver K. , Jones D. Dafydd 
Published: July 2019

AbstractConstruction of artificial higher order protein complexes allows sampling of structural architectures and functional features not accessible by classical monomeric proteins. Here, we combine in silico modelling with expanded genetic code facilitated strain promoted azide-alkyne cycloaddition to construct artificial complexes that are structurally integrated protein dimers and demonstrate functional synergy. Using fluorescent proteins sfGFP and Venus as models, homodimers and heterodimers are constructed that switched ON once assembled and display enhanced spectral properties. Symmetrical crosslinks are found to be important for functional enhancement. The determined molecular structure of one artificial dimer shows that a new long-range polar network comprised mostly of organised water molecules links the two chromophores leading to activation and functional enhancement. Single molecule analysis reveals the dimer is more resistant to photobleaching spending longer times in the ON state. Thus, genetically encoded bioorthogonal chemistry can be used to generate truly integrated artificial protein complexes that enhance function.
A high-voltage concept with sodium-ion conducting β-alumina for magnesium-sodium dual-ion batteries
Authors: Kravchyk Kostiantyn V. , Walter Marc , Kovalenko Maksym V. 
Published: July 2019

AbstractRechargeable magnesium-sodium dual-ion batteries that use dendrite-free magnesium metal as an anode, magnesium-sodium dual-ion electrolyte and sodium-ion cathode are appealing as safe, low-cost systems for large-scale stationary electricity storage. Although substantial advances have been made on magnesium-sodium dual-ion batteries with various sodium-ion cathodes, further development of such batteries is inherently limited by the low electrochemical oxidative stability of known dual-ion electrolytes (2–2.6 V vs. Mg2+/Mg). Here, we examine a magnesium-sodium dual-ion concept, which allows for higher operating voltages of magnesium-sodium dual-ion batteries by using oxidatively stable sodium-ion electrolytes along with a sodium-ion conducting β-alumina membrane on the cathode side. The proposed concept is assessed using a high-voltage Na1.5VPO4.8F0.7 cathode demonstrating a high average discharge voltage of 3.0 V, a cathodic capacity of 110 mAh g−1 and an energy efficiency of 90%.
Optical analogue of the dynamical Casimir effect in a dispersion-oscillating fibre
Authors: Vezzoli Stefano , Mussot Arnaud , Westerberg Niclas , Kudlinski Alexandre , Dinparasti Saleh Hatef , Prain Angus , Biancalana Fabio , Lantz Eric , Faccio Daniele 
Published: July 2019

AbstractThe dynamical Casimir effect is the generation of pairs of real particles or photons from the vacuum as a result of a non-adiabatic change of a system parameter or boundary condition. As opposed to standard parametric amplification where the modulation occurs both in space and in time, this fundamental process requires a pure modulation in time, which makes its detection particularly challenging at optical frequencies. In this paper we experimentally demonstrate a realization of the analogue dynamical Casimir effect in the near-infrared optical regime in a dispersion-oscillating photonic crystal fibre. The experiments are based on the equivalence of the spatial modulation of the fibre core diameter to a pure temporal modulation when this is considered in the co-moving frame of the travelling pump pulse. We provide evidence of optical dynamical Casimir effect by measuring quantum correlations between the spectrally resolved photon pairs and prove their non-classical nature with photon anti-bunching.
Confinement and substrate topography control cell migration in a 3D computational model
Authors: Winkler Benjamin , Aranson Igor S. , Ziebert Falko 
Published: July 2019

AbstractCell movement in vivo is typically characterized by strong confinement and heterogeneous, three-dimensional environments. Such external constraints on cell motility are known to play important roles in many vital processes e.g. during development, differentiation, and the immune response, as well as in pathologies like cancer metastasis. Here we develop a physics-driven three-dimensional computational modeling framework that describes lamellipodium-based motion of cells in arbitrarily shaped and topographically structured surroundings. We use it to investigate the primary in vitro model scenarios currently studied experimentally: motion in vertical confinement, confinement in microchannels, as well as motion on fibers and on imposed modulations of surface topography. We find that confinement, substrate curvature and topography modulate the cell’s speed, shape and actin organization and can induce changes in the direction of motion along axes defined by the constraints. Our model serves as a benchmark to systematically explore lamellipodium-based motility and its interaction with the environment.
Influenza A matrix protein M1 induces lipid membrane deformation via protein multimerization
Authors: Dahmani Ismail , Ludwig Kai , Chiantia Salvatore 
Published: July 2019

Abstract
The matrix protein M1 of the Influenza A virus (IAV) is supposed to mediate viral assembly and budding at the plasma membrane (PM) of infected cells. In order for a new viral particle to form, the PM lipid bilayer has to bend into a vesicle toward the extracellular side. Studies in cellular models have proposed that different viral proteins might be responsible for inducing membrane curvature in this context (including M1), but a clear consensus has not been reached. In the present study, we use a combination of fluorescence microscopy, cryogenic transmission electron microscopy (cryo-TEM), cryo-electron tomography (cryo-ET) and scanning fluorescence correlation spectroscopy (sFCS) to investigate M1-induced membrane deformation in biophysical models of the PM. Our results indicate that M1 is indeed able to cause membrane curvature in lipid bilayers containing negatively charged lipids, in the absence of other viral components. Furthermore, we prove that protein binding is not sufficient to induce membrane restructuring. Rather, it appears that stable M1–M1 interactions and multimer formation are required in order to alter the bilayer three-dimensional structure, through the formation of a protein scaffold. Finally, our results suggest that, in a physiological context, M1-induced membrane deformation might be modulated by the initial bilayer curvature and the lateral organization of membrane components (i.e. the presence of lipid domains).
Venous Access for Cardiovascular Procedures
Authors: Nemani Lalita , Vikas Medep 
Published: July 2019

AbstractVenous access is an integral and essential part of cardiovascular interventions for both diagnostic and therapeutic procedures, and it can be lifesaving in cardiac emergencies. Peripheral venous access though simple can sometimes be not achieved for multitude of reasons; hence, knowledge of central venous access is important and is an integral part of cardiac interventional training.
TEFL tourism as a form of niche tourism.
Authors: Stainton H. 
Published: July 2019

Abstract

This chapter seeks to identify a number of similarities between TEFL tourism (i.e., tourism that involves teaching English as a foreign language) and various other forms of tourism, placing it firmly in the 'micro-niche' category. The work-leisure binary in TEFL tourism is discussed, as well as TEFL tourism's ties with volunteer tourism. A typology of TEFL tourism is then presented, which includes cultural TEFL tourism, philanthropic TEFL tourism, pro-poor TEFL tourism, educational TEFL tourism, adventure TEFL tourism, and gap-year TEFL tourism.
The education paradox.
Authors: Stainton H. 
Published: July 2019

Abstract

This chapter addresses the issues associated with the convergence of education and tourism in the context of TEFL tourism (i.e., tourism that involves teaching English as a foreign language). Differences in teaching practice between the developed and developing worlds, ethnocentric perceptions of educational provision, the definition of 'teacher', TEFL training and qualifications, and teacher skills and suitability are discussed.
The sustainability of TEFL tourism.
Authors: Stainton H. 
Published: July 2019

Abstract

This chapter provides an overview of sustainability considerations that should be taken into account by operators and academics in TEFL tourism (i.e., tourism that involves teaching English as a foreign language). The chapter discusses: TEFL as a tool for development; TEFL tourism as a tool for poverty reduction; the social, economic, and pedagogic impacts of TEFL tourism; and ethics within TEFL tourism.
The symbolism of sacred space.
Authors: Olsen D. H. 
Published: July 2019

Abstract

This chapter discusses the development and maintenance of sacred spaces and places as defined by institutionalized religion, and how these spaces and places are contested yet also a meeting ground for cross-cultural understanding. The chapter begins by briefly summarizing some of the academic shifts that have taken place over the past few decades regarding the study of sacred space. It then turns to discuss the production and contestation of sacred space with an emphasis on sacred spaces as 'places in motion', before examining how sacred spaces are being used by religious groups for outreach and to promote cross-cultural understanding.
Images as an embodiment of the sacred.
Authors: Ferrer Ventosa R. 
Published: July 2019

Abstract

This chapter focuses on images that allude one way or another to the sacred. Images can be used to express ultimate truths in a more effective way than texts or words, getting round the limitations of texts: illiteracy or the fragmentation in various languages. Through sacred visual art, many metaphysical ideas take shape and can be communicated through symbols and metaphors.
Does a religious tourist need a guide? Interpretation and storytelling in sacred places.
Authors: Duda T. 
Published: July 2019

Abstract

This chapter presents contemporary trends in religious tourism and the role that pilgrimage plays in shaping the knowledge and attitudes related to the religious and spiritual heritage of the region. Based on surveys and direct interviews in the Pomerania region (north-west Poland and north-east Germany), the role of a tourist guide was determined to be an 'interpreter of places and routes, responsible for the provision of an adequate storytelling process'. The chapter also attempts to answer some key questions that trouble contemporary researchers studying the problem of interpretation in tourism, associated with the phenomenon of pilgrimage and/or religious tourism.
Updating a romantic view? Ruskin's Mornings in Florence.
Authors: Crous-Costa N. 
Published: July 2019

Abstract

This chapter focuses on John Ruskin's guidebook Mornings in Florence (1877). The goal of the chapter is to discuss the feasibility of Ruskin's itinerary in this guidebook today. This exploration not only considers the existence of the sights referred to, most of which are still prominent tourist landmarks today, but additionally the chapter reflects on the interest of using this understanding of the city again from the perspective of different stakeholders.
Collagen-derived dipeptide prolyl hydroxyproline directly binds to Foxg1 to change its conformation and inhibit the interaction with Runx2
Authors: Nomura Kaho , Kimira Yoshifumi , Osawa Yoshihiro , Shimizu Jun , Kataoka-Matsushita Aya , Mano Hiroshi 
Published: July 2019

ABSTRACTCollagen-derived dipeptide prolyl hydroxyproline (Pro-Hyp) is involved in the proliferation and differentiation of various types of cultured cells. To elucidate the mechanism underlying Pro-Hyp actions during osteoblast differentiation, we hypothesized that proteins binding to Pro-Hyp serve to mediate cellular signaling, affecting Runx2 expression. Recently, we performed the characterization of Foxg1, that it enhances Runx2 expression in the presence of Pro-Hyp. Our findings indicate that Pro-Hyp directly binds to the Foxg1 recombinant protein, which leads to the structural alteration of the Foxg1 protein. In addition, Foxg1 appears to interact with Runx2 in the absence of Pro-Hyp, with Pro-Hyp disrupting the interaction between Foxg1 and Runx2. Collectively, our results indicate that the Pro-Hyp bound Foxg1 alters the structured conformation of Foxg1, resulting in conformational changes that lead to dissociation from Runx2. These novel findings suggest that during osteoblast differentiation, Pro-Hyp mediates Runx2 activity though directly binding to Foxg1 and increases Runx2 expression.Abbreviations: CPT: collagen peptide; GST: Glutathione S-transferase; PAGE: Polyacrylamide gel electrophoresis; PCR: Polymerase chain reaction; prolyl hydroxyproline: Pro-Hyp
Magnetocaloric Mn5Si3 and MnFe4Si3 at variable pressure and temperature
Authors: Eich Andreas , Grzechnik Andrzej , Caron Luana , Cheng Yao , Wilden Johanna , Deng Hao , Hutanu Vladimir , Meven Martin , Hanfland Michael , Glazyrin Konstantin , Hering Paul , Herrmann Markus Guido , Ait Haddouch Mohammed , Friese Karen 
Published: July 2019

Abstract
The influence of hydrostatic high pressure on the crystal structures and magnetic properties of magnetocaloric Mn5Si3 and MnFe4Si3 was studied with temperature dependent synchrotron powder diffraction, neutron single-crystal diffraction and magnetization measurements. Mn5Si3 shows no indication for any pressure-induced structural phase transition up to 24.2 GPa at room temperature. MnFe4Si3 exhibits no clear indication for any phase transition at high temperatures (296 K–373 K) and high pressures. Anomalies in the lattice parameter at low temperatures indicate a structural response to magnetic ordering. The gradient of decreasing magnetic transition temperature with increasing pressure is dT
C/dP ≈ −15 K GPa−1. The transition temperature in MnFe4Si3 can be tuned by pressure in the temperature range relevant for applications, while pressure has hardly any detrimental influence on other key features relevant to magnetocaloric applications (the width of hysteresis, saturation magnetization, magnetocrystalline anisotropy).
Analysis of magnetic flux in magneto-rheological damper
Authors: Purandare Snehal , Zambare Hrishikesh , Razban Ali 
Published: July 2019

Abstract
Magnetorheological materials are a class of smart substances whose rheological properties can rapidly be varied by application of a magnetic field. The proposed damper consists of an electromagnet and a piston immersed in MR fluid. When current is applied to the electromagnet, the MR fluid solidifies as its yield stress varies in response to the applied magnetic field. Hence, the generation of a magnetic field is an important phenomenon in MR damper. In this research, the magnetic field generated in the damper was analyzed by applying finite element method using COMSOL Multiphysics and was validated using magnetic circuit theory. A quasi-static, 2D—Axisymmetric model was developed using parametric study by varying current from 0–3 A and the magnetic flux density change generated in the fluid flow gap of MR fluid due to external applied current was evaluated. According to the analytical calculations magnetic flux density generated at MR fluid gap was 0.64 Tesla and when calculated using FEA magnetic flux density generated was 0.61 Tesla for 1A current. There is a difference of 4.8% in the simulated results and analytically calculated results of automotive MR damper due to non linear BH curve consideration in Finite element analysis over linear consideration of BH relation in magnetic circuit theory.
Case report of simultaneous transcatheter mitral valve-in-valve implantation and percutaneous closure of two paravalvular leaks
Authors: Asami Masahiko , Pilgrim Thomas , Windecker Stephan , Praz Fabien 
Published: July 2019

Abstract

Background
Concomitant structural degeneration of surgical mitral bioprostheses and paravalvular leak (PVL) is rare but potentially fatal. Data pertaining to simultaneous transcatheter mitral valve implantation (TMVI) and percutaneous PVL closure are limited, and the optimal treatment strategy remains undetermined. We report a case of simultaneous TMVI and double percutaneous PVL closure in a patient with a degenerated bioprosthetic mitral valve and associated medial and lateral PVLs.

Case summary
A 75-year-old woman who underwent combined aortic (Edwards Perimount Magna 19 mm) and mitral (Edwards Perimount Magna 25 mm) surgical valve replacement 6 years ago was referred for treatment of new-onset orthopnoea and severely reduced exercise capacity. Transoesophageal echocardiography revealed severe mitral stenosis and concomitant moderate to severe mitral regurgitation, originating from two PVLs located medial and lateral from the surgical bioprosthesis. Due to high surgical risk, we performed successful transseptal mitral valve-in-valve (ViV) implantation combined with the closure of two PVLs during the same procedure.

Discussion
Although surgery should be considered as a first-line treatment in this setting, most patients have extremely high or prohibitive surgical risk inherent to repeat open heart surgery. Mitral ViV implantation appears a reasonable treatment option for patients with failed mitral bioprostheses. Furthermore, a recent study of percutaneous PVL closure showed no significant difference in long-term all-cause mortality compared with redo open-heart surgery. Simultaneous TMVI and percutaneous PVL closure appears feasible in selected high-risk patients.
Genes, pathways and risk prediction in Alzheimer’s disease
Authors: Hardy John , Escott-Price Valentina 
Published: July 2019

Abstract
The failure of recent clinical trials in Alzheimer's disease has highlighted the need for the development of a more complete understanding of the pathogenesis of the disorder and also a belief that therapies may only work if given very early in the disease process before overt symptoms occur. The rare, early onset forms of the disease are all caused by mutations which make amyloid deposition a more likely event. Here we discuss the recent data showing that, in contrast, much of the risk of late onset disease is encoded by loci involved in lipid metabolism and/or encoded by microglia. We discuss these finding and suggest that amyloid induced membrane damage may be a key factor in disease and also review the evidence that genome wide genetic analysis can substantially help in the prediction of those individuals at high risk of disease in the general population.
A fresh look at the biodiversity lexicon for fiddler crabs (Decapoda: Brachyura: Ocypodidae). Part 1: Taxonomy
Authors: Rosenberg Michael S 
Published: July 2019

AbstractFiddler crabs (Ocypodidae) have gone through a gradual series of taxonomic revisions and refinements over the last 40 years, culminating most recently with an expansion from a single genus into eleven different genera. I examine the opportunities presented by these revisions with respect to establishing formal names for previously established clades at a variety of taxonomic levels that were otherwise previously impossible to name due to historical compression of these crabs into a single genus, including the establishment or reestablishment of three tribes (Ucini, Gelasimini, and Minucini) and ten subgenera: Uca (Uca), Uca (Acanthoplax), Gelasimus (Gelasimus), Gelasimus (Mesuca), Austruca (Austruca), Austruca (Cuneatuca), Austruca (Sinduca), Tubuca (Tubuca), Tubuca (Australuca), and Tubuca (Angustuca). A previously overlooked synonymy between Gelasimus excisa (Nobili, 1906) and G. neocultrimana (Bott, 1973) is discussed, and the former name is adopted as valid.
Microanatomy of the American Malaria Vector Anopheles aquasalis (Diptera: Culicidae: Anophelinae) Midgut: Ultrastructural and Histochemical Observations
Authors: Baia-da-Silva Djane C , Orfanó Alessandra S , Nacif-Pimenta Rafael , de Melo Fabricio F , Guerra Maria G V B , Lacerda Marcus V G , Monteiro Wuelton M , Pimenta Paulo F P 
Published: July 2019

AbstractThe mosquito gut is divided into foregut, midgut, and hindgut. The midgut functions in storage and digestion of the bloodmeal. This study used light, scanning (SEM), and transmission (TEM) electron microscopy to analyze in detail the microanatomy and morphology of the midgut of nonblood-fed Anopheles aquasalis females. The midgut epithelium is a monolayer of columnar epithelial cells that is composed of two populations: microvillar epithelial cells and basal cells. The microvillar epithelial cells can be further subdivided into light and dark cells, based on their affinities to toluidine blue and their electron density. FITC-labeling of the anterior midgut and posterior midgut with lectins resulted in different fluorescence intensities, indicating differences in carbohydrate residues. SEM revealed a complex muscle network composed of circular and longitudinal fibers that surround the entire midgut. In summary, the use of a diverse set of morphological methods revealed the general microanatomy of the midgut and associated tissues of An. aquasalis, which is a major vector of Plasmodium spp. (Haemosporida: Plasmodiidae) in America.