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10.1177/1465116516680763 | How Changing Conditions Make Us Reconsider The Relationship Between Immigration Attitudes Religion And Eu Attitudes | In a world where attitudes towards immigration and the European Union are at the forefront of political and economic agendas across the continent, this Special Issue is highly relevant and well timed. This Forum article reviews the Special Issue and summarizes lessons learned and identifies open, remaining and new, questions. As a future research agenda, it is advised to pay attention to (a) differentiation in EU attitudes, (b) the role of national political elites, (c) the changing communications environment, and (d) the role of religion and religious attitudes. | [
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems"
]
|
10.1145/2185520.2185540 | How Do Humans Sketch Objects | Humans have used sketching to depict our visual world since prehistoric times. Even today, sketching is possibly the only rendering technique readily available to all humans. This paper is the first large scale exploration of human sketches. We analyze the distribution of non-expert sketches of everyday objects such as 'teapot' or 'car'. We ask humans to sketch objects of a given category and gather 20,000 unique sketches evenly distributed over 250 object categories. With this dataset we perform a perceptual study and find that humans can correctly identify the object category of a sketch 73% of the time. We compare human performance against computational recognition methods. We develop a bag-of-features sketch representation and use multi-class support vector machines, trained on our sketch dataset, to classify sketches. The resulting recognition method is able to identify unknown sketches with 56% accuracy (chance is 0. 4%). Based on the computational model, we demonstrate an interactive sketch recognition system. We release the complete crowd-sourced dataset of sketches to the community. | [
"Computer Science and Informatics",
"The Human Mind and Its Complexity"
]
|
10.1038/s41467-018-04787-4 | Gene flow contributes to diversification of the major fungal pathogen Candida albicans | Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Immunity, Infection and Immunotherapy"
]
|
215808 | Enlarge – energies for local administrations: renovate governance in europe | Co-design and co-production processes are promising horizontal governance tools to innovate public administrations and the public sector in general. In particular, co-design processes aim at improving policy effectiveness by including a wide range of viewpoints in the formulation of public policies and in the design of public services, while co-production processes are designed and managed to involve ‘responsible citizens-users’ in the implementation of the policies and in public service delivery, and aim not only at improving policy effectiveness, but also at sustaining public sector intervention in the recent austerity era, during which governments (especially local governments) must face new social needs and complex problems with decreasing public resources.
Notwithstanding the high potential of these processes as innovative and effective governance tools, practical evidence about their usefulness and sustainability for local administrators is still lacking, and local governments proceed mostly incrementally and unaware of potentials and pitfalls.
ENLARGE project aims to shed some light on the ‘how and why’ issues of co-design and co-production processes through an intense policy dialogue between policy makers, experts in participatory governance and civil society actors. The specific focus is on sustainable energy and more in general all the solutions aiming at generating more efficiency and effectiveness in public services and public endowments.
In detail, the project intends to: EXPLORE the existing models of co-design and co-production of public policies and services; EVALUATE – measures for the assessment of the outcomes; mechanisms and intervening factors favouring the effectiveness of participatory processes; PRODUCE - Raising awareness among public administrators about the options at their disposal and the potential consequences of these choices; COMMUNICATE and DISSEMINATE the project results. | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.15252/msb.20156458 | Frequency modulation of ERK activation dynamics rewires cell fate | Transient versus sustained ERK MAP kinase (MAPK) activation dynamics induce proliferation versus differentiation in response to epidermal (EGF) or nerve (NGF) growth factors in PC-12 cells. Duration of ERK activation has therefore been proposed to specify cell fate decisions. Using a biosensor to measure ERK activation dynamics in single living cells reveals that sustained EGF/NGF application leads to a heterogeneous mix of transient and sustained ERK activation dynamics in distinct cells of the population, different than the population average. EGF biases toward transient, while NGF biases toward sustained ERK activation responses. In contrast, pulsed growth factor application can repeatedly and homogeneously trigger ERK activity transients across the cell population. These datasets enable mathematical modeling to reveal salient features inherent to the MAPK network. Ultimately, this predicts pulsed growth factor stimulation regimes that can bypass the typical feedback activation to rewire the system toward cell differentiation irrespective of growth factor identity. Synopsis Dynamic manipulation of ERK signaling at the single cell level reveals new features of the MAPK network topology and induces robust signaling responses that rewire cell fate decision independently of growth factor identity. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1109/TSP.2015.2488598 | Binary Sparse Coding Of Convolutive Mixtures For Sound Localization And Separation Via Spatialization | We propose a sparse coding approach to address the problem of source-sensor localization and speech reconstruction. This approach relies on designing a dictionary of spatialized signals by projecting the microphone array recordings into the array manifolds characterized for different locations in a reverberant enclosure using the image model. Sparse representation over this dictionary enables identifying the subspace of the actual recordings and its correspondence to the source and sensor locations. The speech signal is reconstructed by inverse filtering the acoustic channels associated to the array manifolds. We provide rigorous analysis on the optimality of speech reconstruction by elucidating the links between inverse filtering and source separation followed by deconvolution. This procedure is evaluated for localization, reconstruction and recognition of simultaneous speech sources using real data recordings. The results demonstrate the effectiveness of the proposed approach and compare favorably against beamforming and independent component analysis techniques. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
W2288875092 | Solid acid catalyzed synthesis of furans from carbohydrates | The alternative feedstock, biomass (particularly lignocelluloses), having the profuse availability, is promising for the synthesis of several value-added chemicals which are currently obtained from fossil feedstock. In this article, the synthesis of two extremely significant furan chemicals viz. furfural and 5-hydroxymethylfurfural (HMF) are discussed. In the synthesis of furans from biomass, numerous challenges, i.e., use of edible sugars as substrates, selectivity to furans, their isolation in pure form, reuse of catalyst, environmental issues, etc., are perceived and in the recent past researchers tried to resolve those by developing advance methodologies. This article comprehensively summarizes the latest progress made in the above-mentioned areas and also provides commentary on the analyses of results, rationale for observed activity and mechanisms, etc. It also discusses future aspects of this work. | [
"Synthetic Chemistry and Materials",
"Products and Processes Engineering"
]
|
996778 | A novel approach to non-invasive and personalized skin cancer diagnosis | French SME-company DAMAE Medical is facing skin cancer worldwide issue by developing the OCTAV Project, a new approach to
dermatological diagnostic based on a disruptive Line-field Confocal Optical Coherence Tomography (LC-OCT) technology, in a novel
hand-held imaging device.
OCTAV is designed to capture in situ images of the skin layers with a cellular resolution. It is used in conjunction with dermoscopy to
provide more accurate diagnosis, leading to fewer biopsies of benign lesions and earlier detection of melanoma (clinical use 1) and
non-melanoma skin cancers (clinical use 2). It may also guide the surgery to provide more accurate presurgical margins (clinical use
3), preventing unnecessarily large scars and reducing the risk of recurrence.
Correlatively, DAMAE is developing a full software solution, based on a data storage cloud-platform, a computer-aided software
designed to assist dermatologists with OCTAV image interpretation, as well as telepathology and patient services.
OCTAV device will initially be used by clinicians as a routine easy-handling diagnostic device in public practices (market segment 1).
Implementation of OCTAV software will enable its adoption by a much larger market, consisting of private practices dermatologists
(market segment 2). The approach will contribute to the development of skin cancer risk patient awareness, while changing the
current paradigm through a timely, performant, and non-invasive approach, and releasing the financial burden on the healthcare
system.
Project OCTAV has successfully completed in 2017 a feasibility phase covered by the SME Instrument Phase 1, resulting in a TRL6
prototype of the technology and a first consolidated atlas of skin cancer clinical images. The main objective of this Phase2 is to
scaleup
the OCTAV solution to TRL9 through industrialization activities and by achieving a definitive market assessment, the clinical
validation and the regulatory approval, before deploying the approach worldwide. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Products and Processes Engineering",
"Computer Science and Informatics"
]
|
279697 | Three-Component Fermi Gas Lattice Experiment | Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics. | [
"Condensed Matter Physics",
"Fundamental Constituents of Matter"
]
|
interreg_3612 | Creation of telecenters to support learning, entrepreneurship and access to IS, in isolated areas | More than 14 million households in remote areas of Europe have difficulties in accessing information and communication technologies (ICTs). Particularly in rural regions tele-density is low compared to urban centres. Despite many programmes focusing on this issue, the so-called digital divide is ever increasing. Until now transfer rates tend to be lower in rural areas which limits the introduction of advanced services, like e-Health and e-Learning, as well as organisational development. The provision of broadband connections through telecentres in remote areas can help to solve this problem. Project partners of TELEACCESS come from regions with shared past experiences concerning ICT and spatial development issues. Aim of the project is to foster the digital culture among rural citizens to enable remote areas the access to the information society. For this, existing local establishments are converted into pilot telecentres. These should function as a hub to provide the local labour force and citizens of all ages with faster access to the Internet. Target groups and beneficiaries of the project are all citizens of the participating regions as well as regional and local authorities, including municipalities, prefectures and other local institutions, such as schools and libraries. | [
"Systems and Communication Engineering",
"Human Mobility, Environment, and Space",
"Computer Science and Informatics"
]
|
10.1016/j.crvi.2013.12.003 | Complement factor H and related proteins in age-related macular degeneration | Age-related macular degeneration (AMD) is the major cause of legal blindness in the industrialized world. Polymorphisms and recently discovered rare mutations of the Complement Factor H gene have been shown to be strongly associated with AMD. The deletion of CFH-related proteins 1 and 3, proteins that share homologous regions with CFH, is found in protective haplotypes. The following is a critical review of the current state of knowledge of the implication of CFH and CFH-related proteins 1 and 3 in AMD. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing",
"Immunity, Infection and Immunotherapy"
]
|
10.1038/s41378-019-0099-5 | Single-cell protein profiling in microchambers with barcoded beads | Abstract
Single-cell profiling provides insights into cellular behaviour that macroscale cell cultures and bulk measurements cannot reveal. In the context of personalized cancer treatment, the profiling of individual tumour cells may lead to higher success rates for therapies by rapidly selecting the most efficacious drugs. Currently, genomic analysis at the single-cell level is available through highly sensitive sequencing approaches. However, the identification and quantification of intracellular or secreted proteins or metabolites remains challenging. Here, we introduce a microfluidic method that facilitates capture, automated data acquisition and the multiplexed quantification of proteins from individual cells. The microfluidic platform comprises 1026 chambers with a volume of 152 pL each, in which single cells and barcoded beads are co-immobilized. We demonstrated multiplexed single-cell protein quantification with three different mammalian cell lines, including two model breast cancer cell lines. We established on-chip immunoassays for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), galectin-3 (Gal-3) and galectin-3 binding protein (Gal-3bp) with detection limits as low as 7. 0 × 104, 2. 3 × 105 and 1. 8 × 103 molecules per cell, respectively. The three investigated cell types had high cytosolic levels of GAPDH and could be clearly differentiated by their expression levels of Gal-3 and Gal-3bp, which are important factors that contribute to cancer metastasis. Because it employed commercially available barcoded beads for this study, our platform could be easily used for the single-cell protein profiling of several hundred different targets. Moreover, this versatile method is applicable to the analysis of bacteria, yeast and mammalian cells and nanometre-sized lipid vesicles. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
SE 9702205 W | BUCKET | Bucket (1) intended to be carried by means of an arm or the like for manoeuvring and comprising a bottom and back part and opposing side parts (4), which parts together from a load space (5) with an opening (6) having an edge part (8) connected to the bottom and edge part and running sideways in the bucket. The bucket is especially characterized in, that said bottom and back part (3) comprises an internal sorting part (9) through, which among other things liquid and comparatively finely dispersed goods, e.g. sand and earth, may pass, as well as an external sealing part (10), which is swingable towards and from the sorting part between a first position, in which the sorting part is substantially exposed, and a second position, in which the sealing part substantially connects to the sorting part. | [
"Products and Processes Engineering"
]
|
10.1007/s11040-014-9164-3 | Phase Transition in the Density of States of Quantum Spin Glasses | We prove that the empirical density of states of quantum spin glasses on arbitrary graphs converges to a normal distribution as long as the maximal degree is negligible compared with the total number of edges. This extends the recent results of Keating et al. (2014) that were proved for graphs with bounded chromatic number and with symmetric coupling distribution. Furthermore, we generalise the result to arbitrary hypergraphs. We test the optimality of our condition on the maximal degree for p-uniform hypergraphs that correspond to p-spin glass Hamiltonians acting on n distinguishable spin- 1/2 particles. At the critical threshold p = n1/2 we find a sharp classical-quantum phase transition between the normal distribution and the Wigner semicircle law. The former is characteristic to classical systems with commuting variables, while the latter is a signature of noncommutative random matrix theory. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
10.1039/c5cc07681a | A metal-mediated boron-centred isomerisation reaction via C–H activation | The terminal borylene ligand is activated by Lewis bases to couple with terminal carbonyl ligands reversibly, initially forming a kinetic coupling product, which isomerises via a borylene migratory insertion to a cyclopentadienyl ligand C–H bond. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1109/JPHOTOV.2018.2846674 | Insulator Materials For Interface Passivation Of Cu In Ga Se 2 Thin Films | In this work, metal–insulator–semiconductor structures were fabricated in order to study different types of insulators, namely, aluminum oxide (Al2O3), silicon nitride, and silicon oxide (SiO x ) to be used as passivation layers in Cu(In,Ga)Se2 (CIGS) thin-film solar cells. The investigated stacks consisted of SLG/Mo/CIGS/insulator/Al. Raman scattering and photoluminescence measurements were done to verify the insulator deposition influence on the CIGS surface. In order to study the electrical properties of the CIGS–insulator interface, capacitance versus conductance and voltage ( C–G–V ) measurements were done to estimate the number and polarity of fixed insulator charges ( Qf ). The density of interface defects ( D it) was estimated from capacitance versus conductance and frequency ( C–G–f ) measurements. This study evidences that the deposition of the insulators at high temperatures (300 °C) and the use of a sputtering technique cause surface modification on the CIGS surface. We found that, by varying the SiO x deposition parameters, it is possible to have opposite charges inside the insulator, which would allow its use in different device architectures. The material with lower D it values was Al2O3 when deposited by sputtering. | [
"Condensed Matter Physics",
"Materials Engineering",
"Synthetic Chemistry and Materials"
]
|
10.1103/PhysRevE.92.032128 | Scaling forms of particle densities for Lévy walks and strong anomalous diffusion | We study the scaling behavior of particle densities for Lévy walks whose transition length r is coupled with the transition time t as |r|∞tα with an exponent α>0. The transition-time distribution behaves as ψ(t)∞t-1-β with β>0. For 1<β<2α and α≥1, particle displacements are characterized by a finite transition time and confinement to |r|<tα while the marginal distribution of transition lengths is heavy tailed. These characteristics give rise to the existence of two scaling forms for the particle density, one that is valid at particle displacements |r|蠐tα and one at |r|≲tα. As a consequence, the Lévy walk displays strong anomalous diffusion in the sense that the average absolute moments (|r|q) scale as tqν(q) with ν(q) piecewise linear above and below a critical value qc. We derive explicit expressions for the scaling forms of the particle densities and determine the scaling of the average absolute moments. We find that (|r|q)∞tqα/β for q<qc=β/α and (|r|q)∞t1+αq-β for q>qc. These results give insight into the possible origins of strong anomalous diffusion and anomalous behaviors in disordered systems in general. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
10.1017/jfm.2018.490 | Suspensions of finite-size neutrally buoyant spheres in turbulent duct flow | We study the turbulent square duct flow of dense suspensions of neutrally buoyant spherical particles. Direct numerical simulations (DNS) are performed in the range of volume fractions $\unicode[STIX]{x1D719}=0{-}0. 2$, using the immersed boundary method (IBM) to account for the dispersed phase. Based on the hydraulic diameter a Reynolds number of 5600 is considered. We observe that for $\unicode[STIX]{x1D719}=0. 05$ and 0. 1, particles preferentially accumulate on the corner bisectors, close to the corners, as also observed for laminar square duct flows of the same duct-to-particle size ratio. At the highest volume fraction, particles preferentially accumulate in the core region. For plane channel flows, in the absence of lateral confinement, particles are found instead to be uniformly distributed across the channel. The intensity of the cross-stream secondary flows increases (with respect to the unladen case) with the volume fraction up to $\unicode[STIX]{x1D719}=0. 1$, as a consequence of the high concentration of particles along the corner bisector. For $\unicode[STIX]{x1D719}=0. 2$ the turbulence activity is reduced and the intensity of the secondary flows reduces to below that of the unladen case. The friction Reynolds number increases with $\unicode[STIX]{x1D719}$ in dilute conditions, as observed for channel flows. However, for $\unicode[STIX]{x1D719}=0. 2$ the mean friction Reynolds number is similar to that for $\unicode[STIX]{x1D719}=0. 1$. By performing the turbulent kinetic energy budget, we see that the turbulence production is enhanced up to $\unicode[STIX]{x1D719}=0. 1$, while for $\unicode[STIX]{x1D719}=0. 2$ the production decreases below the values for $\unicode[STIX]{x1D719}=0. 05$. On the other hand, the dissipation and the transport monotonically increase with $\unicode[STIX]{x1D719}$. The interphase interaction term also contributes positively to the turbulent kinetic energy budget and increases monotonically with $\unicode[STIX]{x1D719}$, in a similar way as the mean transport. Finally, we show that particles move on average faster than the fluid. However, there are regions close to the walls and at the corners where they lag behind it. In particular, for $\unicode[STIX]{x1D719}=0. 05,0. 1$, the slip velocity distribution at the corner bisectors seems correlated to the locations of maximum concentration: the concentration is higher where the slip velocity vanishes. The wall-normal hydrodynamic and collision forces acting on the particles push them away from the corners. The combination of these forces vanishes around the locations of maximum concentration. The total mean forces are generally low along the corner bisectors and at the core, also explaining the concentration distribution for $\unicode[STIX]{x1D719}=0. 2$. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
10.1103/PhysRevD.97.088501 | Comment on Measurements without probabilities in the final state proposal | The final state proposal [G. T. Horowitz and J. M. Maldacena, J. High Energy Phys. 04 (2004) 008JHEPFG1029-847910. 1088/1126-6708/2004/04/008] is an attempt to relax the apparent tension between string theory and semiclassical arguments regarding the unitarity of black hole evaporation. Authors Bousso and Stanford [Phys. Rev. D 89, 044038 (2014)PRVDAQ1550-799810. 1103/PhysRevD. 89. 044038] analyze thought experiments where an infalling observer first verifies the entanglement between early and late Hawking modes and then verifies the interior purification of the same Hawking particle. They claim that "probabilities for outcomes of these measurements are not defined" and therefore suggest that "the final state proposal does not offer a consistent alternative to the firewall hypothesis. " We show, in contrast, that one may define all the relevant probabilities based on the so-called ABL rule [Y. Aharonov, P. G. Bergmann, and J. L. Lebowitz, Phys. Rev. 134, B1410 (1964)PHRVAO0031-899X10. 1103/PhysRev. 134. B1410], which is better suited for this task than the decoherence functional. We thus assert that the analysis of Bousso and Stanford cannot yet rule out the final state proposal. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
10.1007/978-3-319-18320-6_1 | Motorway Traffic Flow Optimisation In Presence Of Vehicle Automation And Communication Systems | This paper describes a novel approach for defining optimal strategies in motorway traffic flow control, considering that a portion of vehicles are equipped with Vehicle Automation and Communication Systems (VACS). An optimisation problem, formulated as a convex Quadratic Programming (QP) problem, is developed with the purpose of minimising traffic congestion. The proposed problem is based on a first-order macroscopic traffic flow model able to capture the lane changing and the capacity drop phenomena. An application example demonstrates the achievable improvements if the vehicles travelling on the motorway are influenced by the control actions computed as a solution of the optimisation problem. | [
"Systems and Communication Engineering",
"Products and Processes Engineering",
"Mathematics"
]
|
2715462 | Texad – tailoring exosomes for autoimmune diseases | Exogenus Therapeutics is a drug development company using an exosome-based platform technology to develop an innovative pipeline of therapeutic products. Exogenus’ scientific team has pioneer research work in the area of Umbilical Cord Blood (UCB)-derived Extracellular Vesicles (EVs) clinical application. Among EVs, exosomes are nanosized vesicles (30-150nm) released from all types of cells responsible for cell-to-cell communication. Exogenus’ technology makes use of UCB cells preconditioned in ischemia, which secrete EVs enriched in pro-regenerative, anti-inflammatory and immunomodulatory biomolecules. Based on immunomodulatory properties of the lead biological active agent under development (Exo-101), and its capacity to increase immunotolerance, the company is investigating the potential of these vesicles for the treatment of autoimmune diseases. There are more than 80 different autoimmune diseases (AD) and a prevalence of more than 50 million people in the US alone. There is a high unmet need for most of these diseases, especially regarding safer treatments with less secondary effects. Based on their proprietary vesicles derived from UCB, Exogenus aims to develop a new generation of biologics for AD, with high efficacy and less secondary effects. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W2557603595 | Stochastic Impacts of Metaheuristics from the Toaster to the Turbine [Technology Leaders] | Okay, let's be honest-there's pretty much nothing on metaheuristics in this article other than one short section, so don't let the title distract you. The focus of this issue of IEEE Electrification Magazine and of this article is on understanding and demonstrating how transactive energy systems can have an impact on nonbulk power applications. So what does that include? Well, as it turns out, a lot. The bulk power system with its larger generators and high-voltage transmission lines requires lots of planning, investment, and maintenance. These are assets that have lives measured in decades, and much of their topology is relatively fixed. The bulk system is also well monitored and heavily networked, i.e., there are multiple paths for the electricity to flow, and therefore alternative paths for power flow in the event of a disturbance. | [
"Systems and Communication Engineering",
"Products and Processes Engineering"
]
|
10.1090/conm/658/13132 | Multi-frequency acousto-electromagnetic tomography | This paper focuses on the acousto-electromagnetic tomography, a recently introduced hybrid imaging technique. In a previous work, the reconstruction of the electric permittivity of the medium from internal data was achieved under the Born approximation assumption. In this work, we tackle the general problem by a Landweber iteration algorithm. The convergence of such scheme is guaranteed with the use of a multiple frequency approach, that ensures uniqueness and stability for the corresponding linearized inverse problem. Numerical simulations are presented. | [
"Systems and Communication Engineering",
"Condensed Matter Physics",
"Mathematics"
]
|
884566 | Pure spin currents generated by surface acoustic waves | The ability of spin-polarized currents to interact with magnetic states has strongly impacted computation technologies, being exploited by read-heads and by writing–heads on spin-transfer-torque MRAM memories. Today, the most active field in spintronics aims at the generation of pure spin currents, which differ from spin-polarized currents in that they do not involve net flow of charge. Thus, Joule heat losses and Oersted fields are drastically cut down increasing the stability and reducing the energy consumption of electronic nano-devices. The two main strategies to generate spin currents are focused on (i) the spin-pumping effect arising from magnetization excitations in a ferromagnet, and (ii) the spin Seebeck effect. The latter is particularly interesting, since it involves temperature gradients to create the spin currents. Thus, any generation of heat dissipation –usually unwelcome in electronic devices– would be harnessed to produce useful spin currents by creating temperature gradients. The downside is that heat dissipation is a non-directional phenomenon, spreading slowly in all directions, which makes it unattractive for applications. Interestingly, surface acoustic waves (SAW) are fast and strongly directional strain waves that produce local and directional heat, which could eventually be used to generate spin currents through spin Seebeck effect. Moreover, SAWs can dynamically couple by strain to nano-magnets leading to spin excitations that could also be exploited to generate spin currents through spin pumping. Finally, SAWs constitutes an energy efficient technology well established in commercial applications. Therefore, by using SAWs the two strategies to generate spin currents can be contrived to cooperate in an energy-efficient way extremely appealing for the implementation of pure spin currents in commercial devices. In this project we propose to develop the proof of concept of a spintronic nano-device based on pure spin currents created by SAWs. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Materials Engineering"
]
|
835312 | Plasticity of the Pluripotency Network | A few days after fertilisation mammalian embryos form a blastocyst comprised of three tissues; trophoblast and hypoblast are the forebears of extraembryonic structures, while naive epiblast cell are the pluripotent source of the embryo proper. Classical mouse embryological studies indicate that lineage potencies are determined concomitant with segregation of the three founder tissues. Textbook definitions of pluripotency thus exclude extraembryonic potential. Consistent with this paradigm, mouse embryonic stem cells are generally ineffective in producing trophoblast or hypoblast derivatives. However, we have discovered that human naïve pluripotent cells have high intrinsic competence for trophoblast formation. Furthermore, unlike in mouse, extraembryonic transcription factors are present in human epiblast in vivo. These findings challenge the dogma of early lineage restriction but may be compatible with the ancestral origin of pluripotency. We hypothesise that extraembryonic plasticity underlaid by entwined regulatory networks is the evolutionary template of pluripotency. Consequently, signal modulation to suppress extraembryonic specification may be crucial for capture of stem cells representative of naïve epiblast in most mammals. We will examine human and non-human primates, farm animals in which embryos undergo extended development before implantation, and a marsupial in which pluripotent cells are generated from the trophoblast. In a cross-disciplinary approach we will employ transcriptomics, embryo and stem cell experimentation, and formal computational modelling to uncover the core biological program moulded by evolution into different forms. We aim to establish hitherto elusive chimaera-competent embryonic stem cells from species of importance for research, biomedical applications and livestock improvement. We will obtain fresh insight into the molecular logic governing early development, lineage plasticity, pluripotent identity, and stem cell self-renewal. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1007/JHEP06(2013)113 | Naturalness Of Light Neutralino Dark Matter In Pmssm After Lhc Xenon100 And Planck Data | We examine the possibility of a light (below 46 GeV) neutralino dark matter (DM) candidate within the 19-parameter phenomenological Minimal Supersymmetric Standard Model (pMSSM) in the light of various recent experimental results, especially from the LHC, XENON100, and Planck. We also study the extent of electroweak fine-tuning for such a light neutralino scenario in view of the null results from the searches for supersymmetry so far. Using a Markov Chain Monte Carlo likelihood analysis of the full pMSSM parameter space, we find that a neutralino DM with mass ≳ 10 GeV can in principle still satisfy all the existing constraints. Our light neutralino solutions can be broadly divided into two regions: (i) The solutions in the 10–30 GeV neutralino mass range are highly fine-tuned and require the existence of light selectrons (below 100 GeV) in order to satisfy the observed DM relic density. We note that these are not yet conclusively ruled out by the existing LEP/LHC results, and a dedicated analysis valid for a non-unified gaugino mass spectrum is required to exclude this possibility. (ii) The solutions with low fine-tuning are mainly in the 30–46 GeV neutralino mass range. However, a major portion of it is already ruled out by the latest XENON100 upper limits on its spin-independent direct detection cross section, and the rest of the allowed points are within the XENON1T projected limit. Thus, we show that the allowed MSSM parameter space for a light neutralino DM below the LEP limit of 46 GeV, possible in supersymmetric models without gaugino mass unification, could be completely accessible in near future. This might be useful in view of the recent claims for positive hints of a DM signal in some direct detection experiments. | [
"Fundamental Constituents of Matter"
]
|
10.1039/c7ta09973h | Towards centimeter thick transparent wood through interface manipulation | A centimeter-thick transparent wood structure was realized through interface manipulation. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
W1992213766 | Happiness is Not Fun: Godard, the 20th Century, and Badiou | "Godard is the most contemporary of directors, one who has never set a film in the past. Yet since the 1990s he has produced a whole cycle of works whose tones are retrospective, memorial, elegaic. These include JLG/JLG:Auto-portrait du Décembre (1995), the much-discussed Histoire(s) du Cinèma (begun in 1988, completed in 1998) 2 x 50 Years of French Cinema (commissioned by the BFI for the centennial of cinema in 1995), The Old Place (commissioned by the Museum of Modern Art in 1999), On the Origin of the Twenty-First Century (commissioned by the Cannes Film Festival for the year 2000), Dans Le Noir du Temps (a contribution to the 2002 compilation film Ten Minutes Older), and the 2006 Centre Pompidou exhibition “Travels in Utopia.” This last was a retrospective in the conventional sense (screenings of four decades worth of film and video by Godard, Godard/Gorin, Godard/Mièville, etc), but was also retrospective as an installation, divided into three spaces identified as hier, l’avant-hier, and aujourd’hui (yesterday, the day before yesterday, and today), with tomorrow notable for its absence..." | [
"Texts and Concepts",
"Studies of Cultures and Arts"
]
|
10.1364/OE.20.025077 | Tm Doped Fiber Laser Mode Locked By Graphene Polymer Composite | We demonstrate mode-locking of a thulium-doped fiber laser operating at 1. 94 μm, using a graphene-polymer based saturable absorber. The laser outputs 3. 6 ps pulses, with ~0. 4 nJ energy and an amplitude fluctuation ~0. 5%, at 6. 46 MHz. This is a simple, low-cost, stable and convenient laser oscillator for applications where eye-safe and low-photon-energy light sources are required, such as sensing and biomedical diagnostics. | [
"Condensed Matter Physics",
"Systems and Communication Engineering",
"Materials Engineering"
]
|
10.1371/journal.pone.0117442 | The effect of life history on retroviral genome invasions | Endogenous retroviruses (ERV), or the remnants of past retroviral infections that are no longer active, are found in the genomes of most vertebrates, typically constituting approximately 10% of the genome. In some vertebrates, particularly in shorter-lived species like rodents, it is not unusual to find active endogenous retroviruses. In longer-lived species, including humans where substantial effort has been invested in searching for active ERVs, it is unusual to find them; to date none have been found in humans. Presumably the chance of detecting an active ERV infection is a function of the length of an ERV epidemic. Intuitively, given that ERVs or signatures of past ERV infections are passed from parents to offspring, we might expect to detect more active ERVs in species with longer generation times, as it should take more years for an infection to run its course in longer than in shorter lived species. This means the observation of more active ERV infections in shorter compared to longerlived species is paradoxical. We explore this paradox using a modeling approach to investigate factors that influence ERV epidemic length. Our simple epidemiological model may explain why we find evidence of active ERV infections in shorter rather than longerlived species. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution"
]
|
10.1007/s00334-019-00726-5 | Compositional turnover and variation in Eemian pollen sequences in Europe | The Eemian interglacial represents a natural experiment on how past vegetation with negligible human impact responded to amplified temperature changes compared to the Holocene. Here, we assemble 47 carefully selected Eemian pollen sequences from Europe to explore geographical patterns of (1) total compositional turnover and total variation for each sequence and (2) stratigraphical turnover between samples within each sequence using detrended canonical correspondence analysis, multivariate regression trees, and principal curves. Our synthesis shows that turnover and variation are highest in central Europe (47–55°N), low in southern Europe (south of 45°N), and lowest in the north (above 60°N). These results provide a basis for developing hypotheses about causes of vegetation change during the Eemian and their possible drivers. | [
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
]
|
232640 | Imaging regulatory pathways of angiogenesis | Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
10.1038/s41467-018-05315-0 | Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens | Immunotherapy is emerging as a new pillar of cancer treatment with potential to cure. However, many patients still fail to respond to these therapies. Among the underlying factors, an immunosuppressive tumor microenvironment (TME) plays a major role. Here we show that monocyte-mediated gene delivery of IFNα inhibits leukemia in a mouse model. IFN gene therapy counteracts leukemia-induced expansion of immunosuppressive myeloid cells and imposes an immunostimulatory program to the TME, as shown by bulk and single-cell transcriptome analyses. This reprogramming promotes T-cell priming and effector function against multiple surrogate tumor-specific antigens, inhibiting leukemia growth in our experimental model. Durable responses are observed in a fraction of mice and are further increased combining gene therapy with checkpoint blockers. Furthermore, IFN gene therapy strongly enhances anti-tumor activity of adoptively transferred T cells engineered with tumor-specific TCR or CAR, overcoming suppressive signals in the leukemia TME. These findings warrant further investigations on the potential development of our gene therapy strategy towards clinical testing. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W1976605195 | High Temperature and Salinity Enhance Soil Nitrogen Mineralization in a Tidal Freshwater Marsh | Soil nitrogen (N) mineralization in wetlands is sensitive to various environmental factors. To compare the effects of salinity and temperature on N mineralization, wetland soils from a tidal freshwater marsh locating in the Yellow River Delta was incubated over a 48-d anaerobic incubation period under four salinity concentrations (0, 10, 20 and 35‰) and four temperature levels (10, 20, 30 and 40°C). The results suggested that accumulated ammonium nitrogen (NH4+-N) increased with increasing incubation time under all salinity concentrations. Higher temperatures and salinities significantly enhanced soil N mineralization except for a short-term (≈10 days) inhibiting effect found under 35‰ salinity. The incubation time, temperature, salinity and their interactions exhibited significant effects on N mineralization (P<0.001) except the interactive effect of salinity and temperature (P>0.05), while temperature exhibited the greatest effect (P<0.001). Meanwhile, N mineralization processes were simulated using both an effective accumulated temperature model and a one-pool model. Both models fit well with the simulation of soil N mineralization process in the coastal freshwater wetlands under a range of 30 to 40°C (R2 = 0.88-0.99, P<0.01). Our results indicated that an enhanced NH4+-N release with increasing temperature and salinity deriving from the projected global warming could have profound effects on nutrient cycling in coastal wetland ecosystems. | [
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
]
|
W2326102742 | Integrating Ethico-Cultural Derivatives for Sustainable Global SMES : A Case Study of Africa and Asia | One of the key variables in the analysis of small and medium enterprises (SME’s) is the influence of ethico-cultural derivatives and its impacts on overall global business growth and development. The paper highlights some essential ethico-cultural derivatives that have influenced small and medium enterprise (SME) operations both in Africa and Asia. The paper posits that despite the uniqueness and the importance of these ethico-cultural derivatives in SMEs activities across the two regions, the exigencies of global SMEs development has make it imperative to have an SME ethico-cultural meeting points for sustainable global SMEs. The paper identifies how ethico-cultural variances in Africa and Asia SME operations can be integrated and harnessed for effective inter-regional growth as prelude to globally sustainable SMEs. | [
"The Social World and Its Interactions",
"Individuals, Markets and Organisations"
]
|
10.1364/OE.23.015278 | Cep Stable Tunable Thz Emission Originating From Laser Waveform Controlled Sub Cycle Plasma Electron Bursts | We study THz-emission from a plasma driven by an incommensurate-frequency two-colour laser field. A semi-classical transient electron current model is derived from a fully quantum-mechanical description of the emission process in terms of sub-cycle field-ionization followed by continuum-continuum electron transitions. For the experiment, a CEP-locked laser and a near-degenerate optical parametric amplifier are used to produce two-colour pulses that consist of the fundamental and its near-half frequency. By choosing two incommensurate frequencies, the frequency of the CEP-stable THz-emission can be continuously tuned into the mid-IR range. This measured frequency dependence of the THz-emission is found to be consistent with the semi-classical transient electron current model, similar to the Brunel mechanism of harmonic generation. | [
"Physical and Analytical Chemical Sciences",
"Fundamental Constituents of Matter"
]
|
10.1007/978-94-017-8978-3_13 | Impact Of Dust Radiative Forcing Upon Climate | Dust aerosols perturb the atmospheric radiative flux at both solar and thermal wavelengths, altering the energy and water cycles. The climate adjusts by redistributing energy and moisture, so that local temperature perturbations, for example, depend upon the forcing over the entire extent of the perturbed circulation. Within regions frequently mixed by deep convection, including the deep tropics, dust particles perturb the surface air temperature primarily through radiative forcing at the top of the atmosphere (TOA). Many models predict that dust reduces global precipitation. This reduction is typically attributed to the decrease of surface evaporation in response to dimming of the surface. A counterexample is presented, where greater shortwave absorption by dust increases evaporation and precipitation despite greater dimming of the surface. This is attributed to the dependence of surface evaporation upon TOA forcing through its influence upon surface temperature and humidity. Perturbations by dust to the surface wind speed and vegetation (through precipitation anomalies) feed back upon the dust aerosol concentration. The current uncertainty of radiative forcing attributed to dust and the resulting range of climate perturbations calculated by models remain a useful test of our understanding of the mechanisms relating dust radiative forcing to the climate response. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
10.1088/1742-5468/2011/03/P03002 | On The Solution Of A Solvable Model Of An Ideal Glass Of Hard Spheres Displaying A Jamming Transition | We discuss the analytical solution through the cavity method of a mean field model that displays at the same time an ideal glass transition and a set of jamming points. We establish the equations describing this system, and we discuss some approximate analytical solutions and a numerical strategy to solve them exactly. We compare these methods and we get insight into the reliability of the theory for the description of finite dimensional hard spheres. | [
"Condensed Matter Physics",
"Mathematics"
]
|
10.1111/j.1755-0998.2011.03026.x | Analysing recombination in nucleotide sequences | Throughout the living world, genetic recombination and nucleotide substitution are the primary processes that create the genetic variation upon which natural selection acts. Just as analyses of substitution patterns can reveal a great deal about evolution, so too can analyses of recombination. Evidence of genetic recombination within the genomes of apparently asexual species can equate with evidence of cryptic sexuality. In sexually reproducing species, nonrandom patterns of sequence exchange can provide direct evidence of population subdivisions that prevent certain individuals from mating. Although an interesting topic in its own right, an important reason for analysing recombination is to account for its potentially disruptive influences on various phylogenetic-based molecular evolution analyses. Specifically, the evolutionary histories of recombinant sequences cannot be accurately described by standard bifurcating phylogenetic trees. Taking recombination into account can therefore be pivotal to the success of selection, molecular clock and various other analyses that require adequate modelling of shared ancestry and draw increased power from accurately inferred phylogenetic trees. Here, we review various computational approaches to studying recombination and provide guidelines both on how to gain insights into this important evolutionary process and on how it can be properly accounted for during molecular evolution studies. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
]
|
10.1007/s00170-015-7748-0 | Experimental validation of appropriate axial immersions for helical mills | The forced periodic vibrations of milling processes with helical tools are modelled and analysed. By means of analytical and numerical techniques, the so-called superchart of milling is constructed that includes the conventional stability chart with the stability lobes and also the amplitudes of the stable forced vibrations, which is correlated to many surface quality numbers like surface location error, surface waviness and surface roughness. The existences of trivial and non-trivial appropriate axial immersions are presented for a single degree of freedom mechanical model of the machine tool structure. At these appropriate axial immersion parameters, if the cutting is stable, the surface quality parameters will be also optimal even in those spindle speed domains where the system is near to resonance and the cutting efficiency is high. Experiments are performed with a large industrial milling machine using a flexible test rig with an essential flexibility in one direction. The calculated and the measured forced vibration signals in the stable domains of the stability chart are in good correlation, which validates the simple analytical predictions for the non-trivial appropriate axial immersion parameters. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
W4280551403 | Crimean-Congo hemorrhagic fever: a growing threat to Europe | Tick-borne infectious diseases are increasing, driven by geographic expansion of ticks. Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the family Nairoviridae that poses serious threat to public health. CCHFV can cause severe forms of hemorrhagic fever with high case fatality rates (CFR) (10-40%) and can be transmitted from human to human. Until a few years ago, no cases of CCHF had been reported in western Europe. However, high seropositivity rates in wildlife and detection of multiple strains of CCHFV in ticks in Spain suggest that CCHFV enzootic cycle has been established in some areas of southwestern Europe. As far as CCHFV-associated morbidity and mortality are concerned, there are no approved therapeutic options or US/EU licensed vaccines for treatment. Here we discuss some eco-epidemiological aspects as well as public health and socio-economic impacts associated with CCHFV circulation and outbreaks. We also emphasize that it has become essential to identify key inter-species transmission processes of this group of pathogens, to understand basic molecular mechanisms of their replication, and to define their pathogenic potentials.Partout dans le monde, les maladies infectieuses transmises par les tiques sont en augmentation, en raison de l’expansion géographique de ces dernières. Le virus de la fièvre hémorragique de Crimée-Congo (CCHFV) est un virus de la famille des Nairoviridae transmis par les tiques et constitue une menace importante pour la santé publique. Il est responsable de graves fièvres hémorragiques associées à des taux de létalité élevés (10–40%), une transmission d’homme à homme possible et une absence d’options thérapeutiques approuvées ou de vaccins homologués en Espagne et dans l’Union européenne. Jusqu’à il y a quelques années, aucun cas de CCHFV n’avait été signalé en Europe occidentale. Cependant, les taux élevés de séroprévalence chez les animaux sauvages et la détection de multiples souches du CCHFV chez des tiques en Espagne suggèrent que le cycle enzootique du CCHFV s’est déjà établi dans certaines régions du sud-ouest de l’Europe. Outre la morbidité et la mortalité associées à la FHCC, il n’existe pas d’options thérapeutiques approuvées ni de vaccins homologués aux États-Unis et dans l’UE pour son traitement. Nous discutons ici des aspects éco-épidémiologiques ainsi que des impacts socio-économiques et de santé publique associés à la circulation et aux foyers du FHCC. Nous soulignons également qu’il est maintenant devenu essentiel d’identifier les principaux processus de transmission inter-espèces de ce groupe d’agents pathogènes, de comprendre les mécanismes moléculaires de leur réplication et de définir leur potentiel pathogène. | [
"Immunity, Infection and Immunotherapy",
"Environmental Biology, Ecology and Evolution"
]
|
10.1016/j.healthpol.2019.03.012 | A review of attitudes towards the reuse of health data among people in the European Union: The primacy of purpose and the common good | Health data are used for still more purposes, and policies are enacted to facilitate data reuse within the European Union. This literature synthesis explores attitudes among people living in the European Union towards the use of health data for purposes other than treatment. Our findings indicate that while a majority hold positive attitudes towards the use of health data for multiple purposes, the positive attitudes are typically conditional on the expectation that data will be used to further the common good. Concerns evolve around the commercialisation of data, data security and the use of data against the interests of the people providing the data. Studies of these issues are limited geographically as well as in scope. We therefore identify a need for cross-national exploration of attitudes among people living in the European Union to inform future policies in health data governance. | [
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems"
]
|
10.15252/embj.201899697 | Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice | Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin-associated muscle-specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo. In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein. Notably, several Charme-sensitive genes are associated with human cardiomyopathies and Charme depletion in mice results in a peculiar cardiac remodeling phenotype with changes in size, structure, and shape of the heart. Moreover, the existence of an orthologous transcript in human, regulating the same subset of target genes, suggests an important and evolutionarily conserved function for Charme. Altogether, these data describe a new example of a chromatin-associated lncRNA regulating the robustness of skeletal and cardiac myogenesis. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W1777628566 | Exploiting Feature and Class Relationships in Video Categorization with Regularized Deep Neural Networks | In this paper, we study the challenging problem of categorizing videos according to high-level semantics such as the existence of a particular human action or a complex event. Although extensive efforts have been devoted in recent years, most existing works combined multiple video features using simple fusion strategies and neglected the utilization of inter-class semantic relationships. This paper proposes a novel unified framework that jointly exploits the feature relationships and the class relationships for improved categorization performance. Specifically, these two types of relationships are estimated and utilized by rigorously imposing regularizations in the learning process of a deep neural network (DNN). Such a regularized DNN (rDNN) can be efficiently realized using a GPU-based implementation with an affordable training cost. Through arming the DNN with better capability of harnessing both the feature and the class relationships, the proposed rDNN is more suitable for modeling video semantics. With extensive experimental evaluations, we show that rDNN produces superior performance over several state-of-the-art approaches. On the well-known Hollywood2 and Columbia Consumer Video benchmarks, we obtain very competitive results: 66.9\% and 73.5\% respectively in terms of mean average precision. In addition, to substantially evaluate our rDNN and stimulate future research on large scale video categorization, we collect and release a new benchmark dataset, called FCVID, which contains 91,223 Internet videos and 239 manually annotated categories. | [
"Computer Science and Informatics"
]
|
10.1038/ncomms9942 | Carbon-depleted outer core revealed by sound velocity measurements of liquid iron-carbon alloy | The relative abundance of light elements in the Earth's core has long been controversial. Recently, the presence of carbon in the core has been emphasized, because the density and sound velocities of the inner core may be consistent with solid Fe7C3. Here we report the longitudinal wave velocity of liquid Fe84C16 up to 70GPa based on inelastic X-ray scattering measurements. We find the velocity to be substantially slower than that of solid iron and Fe3C and to be faster than that of liquid iron. The thermodynamic equation of state for liquid Fe84C16 is also obtained from the velocity data combined with previous density measurements at 1 bar. The longitudinal velocity of the outer core, about 4% faster than that of liquid iron, is consistent with the presence of 4-5 at. % carbon. However, that amount of carbon is too small to account for the outer core density deficit, suggesting that carbon cannot be a predominant light element in the core. | [
"Condensed Matter Physics",
"Earth System Science"
]
|
10.1021/acssynbio.0c00111 | Inducible Expression Systems Based on Xenogeneic Silencing and Counter-Silencing and Design of a Metabolic Toggle Switch | Inducible expression systems represent key modules in regulatory circuit design and metabolic engineering approaches. However, established systems are often limited in terms of applications due to high background expression levels and inducer toxicity. In bacteria, xenogeneic silencing (XS) proteins are involved in the tight control of horizontally acquired, AT-rich DNA. The action of XS proteins may be opposed by interference with a specific transcription factor, resulting in the phenomenon of counter-silencing, thereby activating gene expression. In this study, we harnessed this principle for the construction of a synthetic promoter library consisting of phage promoters targeted by the Lsr2-like XS protein CgpS of Corynebacterium glutamicum. Counter-silencing was achieved by inserting the operator sequence of the gluconate-responsive transcription factor GntR. The GntR-dependent promoter library is comprised of 28 activated and 16 repressed regulatory elements featuring effector-dependent tunability. For selected candidates, background expression levels were confirmed to be significantly reduced in comparison to established heterologous expression systems. Finally, a GntR-dependent metabolic toggle switch was implemented in a C. glutamicum l-valine production strain allowing the dynamic redirection of carbon flux between biomass and product formation. | [
"Biotechnology and Biosystems Engineering",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.3390/vetsci7030127 | Longitudinal Volumetric Assessment of Ventricular Enlargement in Pet Dogs Trained for Functional Magnetic Resonance Imaging (fMRI) Studies | Background: Recent studies suggest that clinically sound ventriculomegaly in dogs could be a preliminary form of the clinically significant hydrocephalus. We evaluated changes of ventricular volumes in awake functional magnetic resonance imaging (fMRI) trained dogs with indirectly assessed cognitive abilities over time (thus avoiding the use of anaesthetics, which can alter the pressure). Our research question was whether ventricular enlargement developing over time would have any detrimental effect on staying still while being scanned; which can be extrapolated to the ability to pay attention and to exert inhibition. Methods: Seven healthy dogs, 2–8 years old at the baseline scan and 4 years older at rescan, participated in a rigorous and gradual training for staying motionless (<2 mm) in the magnetic resonance (MR) scanner without any sedation during 6 minute-long structural MR sequences. On T1 structural images, volumetric analyses of the lateral ventricles were completed by software guided semi-automated tissue-type segmentations performed with FMRIB Software Library (FSL, Analysis Group, Oxford, UK). Results and conclusion: We report significant enlargement for both ventricles (left: 47. 46 %, right: 46. 07 %) over time while dogs retained high levels of attention and inhibition. The results suggest that even considerable ventricular enlargement arising during normal aging does not necessarily reflect observable pathological changes in behavior. | [
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing"
]
|
10.3390/ijgi8080347 | Incorporating Topological Representation in 3D City Models | 3D city models are being extensively used in applications such as evacuation scenarios and energy consumption estimation. The main standard for 3D city models is the CityGML data model which can be encoded through the CityJSON data format. CityGML and CityJSON use polygonal modelling in order to represent geometries. True topological data structures have proven to be more computationally efficient for geometric analysis compared to polygonal modelling. In a previous study, we have introduced a method to topologically reconstruct CityGML models while maintaining the semantic information of the dataset, based solely on the combinatorial map (C-Map) data structure. As a result of the limitations of C-Map’s semantic representation mechanism, the resulting datasets could suffer either from semantic information loss or the redundant repetition of them. In this article, we propose a solution for a more efficient representation of geometry, topology and semantics by incorporating the C-Map data structure into the CityGML data model and implementing a CityJSON extension to encode the C-Map data. In addition, we provide an algorithm for the topological reconstruction of CityJSON datasets to append them according to this extension. Finally, we apply our methodology to three open datasets in order to validate our approach when applied to real-world data. Our results show that the proposed CityJSON extension can represent all geometric information of a city model in a lossless way, providing additional topological information for the objects of the model. | [
"Computer Science and Informatics",
"Products and Processes Engineering"
]
|
10.1002/nme.5987 | One machine, one minute, three billion tetrahedra | This paper presents a new scalable parallelization scheme to generate the 3D Delaunay triangulation of a given set of points. Our first contribution is an efficient serial implementation of the incremental Delaunay insertion algorithm. A simple dedicated data structure, an efficient sorting of the points, and the optimization of the insertion algorithm have permitted to accelerate reference implementations by a factor three. Our second contribution is a multithreaded version of the Delaunay kernel that is able to concurrently insert vertices. Moore curve coordinates are used to partition the point set, avoiding heavy synchronization overheads. Conflicts are managed by modifying the partitions with a simple rescaling of the space-filling curve. The performances of our implementation have been measured on three different processors: an Intel core-i7, an Intel Xeon Phi, and an AMD EPYC, on which we have been able to compute three billion tetrahedra in 53 seconds. This corresponds to a generation rate of over 55 million tetrahedra per second. We finally show how this very efficient parallel Delaunay triangulation can be integrated in a Delaunay refinement mesh generator, which takes as input the triangulated surface boundary of the volume to mesh. | [
"Computer Science and Informatics",
"Mathematics"
]
|
US 2015/0049782 W | DYNAMIC RISER MECHANICAL CONNECTOR | High-strength, fatigue-resistant pipe connectors suitable for use in offshore risers, tendons and pipelines, such as may be connected to floating production systems (FPSs) principally used in the production of oil and gas. The present connectors include tubular pin and box components with mating frusto-conical, concentrically-grooved mating surfaces which threadingly interlock, and non-threaded (e.g., flat) mating surfaces that seal and preload (e.g., preload at least a portion of each component in compression), via axial advancement of the pin component into the box component. In such connectors, axial movement of the pin into the mating box results the in radial expansion of the box and radial contraction of the pin until the concentric thread patterns match and interlockingly snap into the connected position. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
W1486037667 | “My World Has Expanded Even Though I'm Stuck at Home”: Experiences of Individuals With Amyotrophic Lateral Sclerosis Who Use Augmentative and Alternative Communication and Social Media | Purpose This study aimed to expand the current understanding of how persons with amyotrophic lateral sclerosis (pALS) use augmentative and alternative communication and social media to address their communication needs. Method An online focus group was used to investigate the experiences of 9 pALS who use augmentative and alternative communication and social media. Questions posed to the group related to (a) current use of social media, (b) advantages of social media, (c) barriers to independent use, (d) supports to independent use, and (e) recommendations for developers, policy makers, and other pALS. Results Participants primarily reported that use of social media was a beneficial tool that provided increased communication opportunities, connections to communication partners, and networks of support. Specific results are discussed with reference to the research as well as implications for practice and recommendations for future research. Conclusions As individuals with ALS experience loss of function, some communication modes may no longer be viable. Providing access to different modes of communication, including social media, can allow independence, participation and better quality of life. | [
"Neuroscience and Disorders of the Nervous System",
"The Social World and Its Interactions"
]
|
Q6725596 | Custos – a system of environmental awareness for the blind and visually impaired. | Custos’s design consists of constructing a wearable device designed for blind and visually impaired people to replace the sense of vision. The device is designed to analyse the image from cameras placed in specially created glasses, and the result of the analysis is to provide the user with information about their presence. Information about the surroundings will be transmitted through a specially designed haptic vest. In addition, the system aims to improve the quality of life of blind and visually impaired people and increase their independence by replacing vision in everyday activities such as: moving, choosing outfits, pointing and searching for objects. | [
"Computer Science and Informatics",
"Systems and Communication Engineering",
"Products and Processes Engineering"
]
|
222299 | Botsandus - first assistant robot for retail and hospitality | The retail and hospitality sectors have been facing an international increase both in terms of demand and sophistication. However, they are facing a series of issues. For instance, online is threatening retailers, traditional hotels and event attendance, which offer the advantage of convenience, advocacy and smart, real time insights/data. Also, customers have become immune to marketing across all channels. In this context, it is crucial for the companies from these sectors to offer memorable, fund and useful experiences, which is the key to encourage and multiply visits and sales. BotsAndUS intend to take advantage of this context by offering companies that rely on face to face customer interaction a state-of-the-art robot. It is capable to interact with people of various genders and ages, to autonomously approach and engage in conversation, as well as react to emotions, all to offer outstanding customer service. The market size for retail robots will reach 10 billion euros in 2025, the annual reduction in the cost of manufacturing robots able to interact with humans will drop by 26%, whereas there will be 3o times more interactions per day between humans and robots. BotsAndUs aim is to develop a consumer robot, able to autonomously approach and engage in conversation, react to emotions. Our company puts the user at the centre of Human-Robot-Interaction and develops an innovative technology by combining social sciences, human-centred design and cutting-edge engineering. Bo is the first robot that combines various technologies from the ICT sector to obtain a “social robot”, which will be able to optimally interact with customers by engaging in conversations and adapt to various working environments and feedback from people. To ensure successful commercialization, in Phase 1 of SME Instrument, BotsAndUSintends to develop an elaborate feasibility study for Bo robot commercialisation. | [
"Products and Processes Engineering",
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
724356 | Oligopoly Markets and Networks | Via our connections we learn about new ideas, quality of products, new investment opportunities and job opportunities. We influence and are influenced by our circle of friends. Firms are interconnected in complex processes of production and distribution. A firm’s decisions in a supply chain depends on other firms’ choices in the same supply chain, as well as on firms' behaviour in competing chains. Research on networks in the last 20 years has provided a series of tolls to study a system of interconnected economic agents. This project will advance the state of the art by further developing new applications of networks to better understand modern oligopoly markets.
The project is organised into two sub-projects. In sub-project 1 networks will be used to model diffusion and adoption of network goods. Different consumers' network locations will summarise different consumers' level of influence. The objectives are to understand how firms incorporate information about consumers' influence in their marketing strategies—pricing strategy and product design. It will provide a rigorous framework to evaluate how the increasing ability of firms to gather information on consumers’ influence affects outcomes of markets with network effects. In sub-project 2 networks will be used to model how inputs—e.g., intermediary goods and patents—are combined to deliver final goods. Possible applications are supply chains, communication networks and networks of patents. The objectives are to study firms' strategic behaviour, like pricing and R&D investments, in a complex process of production and distribution, and to understand the basic network metrics that are useful to describe market power. This is particularly important to provide a guide to competition authorities and alike when they evaluate mergers in complex interconnected markets. | [
"Individuals, Markets and Organisations",
"Computer Science and Informatics"
]
|
interreg_2600 | Sustainable development of alpine open spaces by enhancing spatial planning governance | Near-natural open spaces are the basis of human well-being, biodiversity and the livelihood of future generations (i.e. all spaces outside of settlements free from modern technical development, extensive traffic, noise). These essential spaces are decreasing in the Alps due to raising human impact and landscape fragmentation. To maintain these open spaces, coherent transnational cooperation of spatial planning in the Alpine Space (AS) is highly necessary to avoid a race to the bottom regarding minimum standards. This fits the EU-goal of an alpswide network of near-natural areas as part of the EUStrategy on Green Infrastructure (GI) and the EU Urban Agenda. OpenSpaceAlps fosters sustainable development in the core AS and the EUSALP area by maintaining open spaces as part of the alpine GI. We strengthen the transnational multi-level spatial governance by improving the capacities of spatial planners e.g. integrating sectoral planning (e.g.nature conservation) and other stakeholders, through the exchange on approaches for open space maintenance. We interlink spatial planning strategies in local and 2 transnational pilot areas and draw conclusions for improving spatial governance at regional, national and transnational levels. Main outputs:
- Alpine Open Spaces Planning Handbook as a tool for spatial planners on how to better incorporate open spaces in land use decision making.
- Basic visualization (i.e. map) for alpswide spatial planning provides a first tool going beyond the regional and national planning tools for better multi-level transnational spatial governance.
- Strategic recommendations for more efficient coordination of maintaining open spaces at all levels.
- Establishing and institutionalizing a transnational cooperation structure for spatial planning experts, the "Alpplan Network".
Beneficiaries: public administrations in charge of spatial and sectoral planning, non-state actors, associations and policy makers. | [
"Human Mobility, Environment, and Space",
"Environmental Biology, Ecology and Evolution",
"Institutions, Governance and Legal Systems"
]
|
W1972605924 | Substitution of tenofovir/emtricitabine for Hepatitis B immune globulin prevents recurrence of Hepatitis B after liver transplantation | Hepatitis B immune globulin (HBIg) with or without nucleos(t)ide analogue (NA) inhibitors has been shown to prevent recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT). However, the use of HBIg has many disadvantages.The present study was performed to determine if converting patients from HBIg ± NA to combination NA therapy could prevent recurrence of HBV.Twenty-one recipients without evidence of HBV recurrence on HBIg ± NA for ≥ 6 months were enrolled. Patients received their last injection of HBIg at the time they initiated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada(®) ) and were followed up for 31.1 ± 9.0 [range 15-47] months.After 1 year, 3 patients (14%) had detectable HBsAg, one of whom was non-compliant. Two of 3 with recurrence cleared HBsAg by last follow-up on TDF/FTC; the non-compliant patient became HBV DNA-undetectable with re-institution of TDF/FTC. TDF/FTC saved $12,469/year over our standard-of-care, monthly intramuscular HBIg/lamivudine. There was no evidence of a general adverse effect of TDF/FTC on renal function. However, 3 patients developed reversible acute renal failure; on renal biopsy, 1 had possible TDF/FTC-induced acute tubular necrosis.Substitution of TDF/FTC for HBIg prevented recurrence of HBV DNA in 100% (20/20) of patients who were compliant with the medication and led to substantial cost savings over HBIg-containing regimens. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
216314 | Reliable capacity provisioning and enhanced remediation for distributed cloud applications | Large-scale computing systems are today built as distributed systems (for reasons of scale, heterogeneity, cost and energy efficiency) where components and services are distributed and accessed remotely through clients and devices. In some systems, in particular latency-sensitive or high availability systems, components are also placed closer to end-users (in, e.g., radio base stations and other systems on the edge of access networks) in order to increase reliability and reduce latency - a style of computing often referred to as edge or fog computing.
However, while recent years have seen significant advances in system instrumentation as well as data centre energy efficiency and automation, computational resources and network capacity are often provisioned using best effort provisioning models and coarse-grained quality of service (QoS) mechanisms, even in state-of-the-art data centres. These limitations are seen as a major hindrance in the face of the coming evolution of(IoT and the networked society, and have even today manifested in, e.g., a limited cloud adoption of systems with high reliability requirements such as telecommunications infrastructure and emergency services systems.
RECAP goes beyond the current state of the art and develop the next generation of cloud/edge/fog computing capacity provisioning via targeted research advances in cloud infrastructure optimization, simulation and automation. Building on advanced machine learning, optimization and simulation techniques. The overarching result of RECAP is the next generation of agile and optimized cloud computing systems. The outcomes of the project will pave the way for a radically novel concept in the provision of cloud services, where services are instantiated and provisioned close to the users that actually need them by self-configurable cloud computing systems. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
10.1073/pnas.1718707115 | Farming the mitochondrial ancestor as a model of endosymbiotic establishment by natural selection | The origin of mitochondria was a major evolutionary transition leading to eukaryotes, and is a hotly debated issue. It is unknown whether mitochondria were acquired early or late, and whether it was captured via phagocytosis or syntrophic integration. We present dynamical models to directly simulate the emergence of mitochondria in an ecoevolutionary context. Our results show that regulated farming of prey bacteria and delayed digestion can facilitate the establishment of stable endosymbiosis if prey-rich and prey-poor periods alternate. Stable endosymbiosis emerges without assuming any initial metabolic benefit provided by the engulfed partner, in a wide range of parameters, despite that during good periods farming is costly. Our approach lends support to the appearance of mitochondria before any metabolic coupling has emerged, but after the evolution of primitive phagocytosis by the urkaryote. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
W2366956286 | Research on Citizen's Satisfaction of Body-building Environment in Greenway——Taking Central Area in Guangzhou as an Example | It is the first time to investigate citizen's satisfaction of body-building environment in Greenway since Greenway of Guangdong has been built in 2010.Methods: document,investigation and mathematical statistics.Result: Two main administrative divisions of Guangzhou about citizen's degree of satisfaction for the body-buil-ding environment in Greenway are low.Regression shows that the degree of satisfaction about the body-building environment is relevant to the improvement of the maintenance of body-building apparatus(estimate=1.21,P=0.0030.05).Conclusion: The degree of citizen's satisfaction about riding environment and body-building hardware facilities was low.The degree of satisfaction about the body-building environment in Greenway can be increased by improving the maintenance of body-building apparatus. | [
"Human Mobility, Environment, and Space",
"The Social World and Its Interactions"
]
|
10.15252/embj.201693889 | FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma | SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCFFBW7α. Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. FBW7 is either mutated or downregulated in medulloblastoma, and in cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Transcriptional profiling of medulloblastoma cells expressing a degradation-resistant SOX9 mutant reveals activation of pro-metastatic genes and genes linked to cisplatin resistance. Finally, we show that pharmacological inhibition of PI3K/AKT/mTOR pathway activity destabilizes SOX9 in a GSK3/FBW7-dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Neuroscience and Disorders of the Nervous System"
]
|
185804 | E-Solar performance analysis and data collection for energy monitoring: an innovative solution based on measures correlation between an autonomous ground-based solar sensor and earth observation data | Is a solar installation working at its full potential or not? This question is more frequently asked these days either by solar farms operators, venture capitalists willing to invest in renewable energy or companies specialized in operations and maintenance. Comparing irradiance data observed from the ground with data coming from relevant geostationary satellite should provide the answer.
e-SPACE Monitoring aims at delivering PV operators with a permanent PV performance assessment on line service. Through a SAAS platform, operators will access data based on measures correlation between a stand-alone ground-based solar irradiance measurement sensor and satellite data coming from geostationary meteorological satellites completed by Sentinel 4 & 5 satellites and Copernicus services.
By using data analysis algorithms, e-SPACE Monitoring’s personalized service will be able to point out discrepancies between the solar data measured on site and the plant’s actual solar production. This information will be used by plant operators to set up personalized Key Performance Indicators showing whether a solar installation is working at its full potential or not and improve the Operations & Maintenance of their PV installations.
In the coming years, e-SPACE Monitoring will enable REUNIWATT to take advantage of the tremendous growth of the installed solar base worldwide and resulting PV monitoring market. REUNIWATT has a huge opportunity to market a service that will benefit thousands of solar operators globally and contribute to the development of solar power efficiency.
The commercialization of the e-SPACE Monitoring will make REUNIWATT the first European company and a worldwide leader in this field with an estimated turnover of about 20 million euros and the creation of 35 new high-level jobs in Europe by 2023. | [
"Products and Processes Engineering",
"Earth System Science",
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1371/journal.pone.0071207 | Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental Malignant Pleural Effusion | Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2) promotes malignant pleural effusion (MPE) formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung adenocarcinoma cells (A549) were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg) were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE. | [
"Immunity, Infection and Immunotherapy",
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W45286323 | High levels of uric acid correlate with decline of glomerular filtration rate in chronic kidney disease. | Clinical studies have suggested that high levels of uric acid may contribute to the development of hypertension and kidney disease. However the relation between uric acid and chronic kidney disease (CKD) has been inconsistent.To examine the association between plasma concentration of uric acid, and estimated glomerular filtration rate (GFR) in CKD subjects.In a cross-sectional study, authors surveyed 5,558 subjects, but only 750 CKD subjects in whom GFR was between 15 and 60 ml/min/1.73 m2 were included in the study. The GFR values were calculated by Cockcroft-Gault formula.There were 65.5% males, mean age of 50.29 +/- 6.39 years and body mass index (BMI) of 21.68 +/- 2.64 kg/m2. The mean value of estimated GFR was 53.86 +/- 6.29 ml/min/1.73 m2. In subjects with serum uric acid fourth quartile displayed significantly higher BMI, higher systolic blood pressure (BP), higher diastolic BP, higher BUN, and higher serum creatinine, and lower estimated GFR as compared with the three lower quartiles. The correlation analysis showed that estimated GFR was negatively correlated with serum uric acid (r = -0.208, p < 0.01), age (r = -0.171, p < 0.01), systolic BP (r = -0.148, p < 0.01) and BMI (r = -0.147, p < 0.01). Multiple regression analysis, the presence of high serum uric acid levels were independently associated with a decline of GFR.In CKD subjects, high levels of uric acid were independent associated with GFR decline. Our finding suggests that early detection and prevention on hyperuricemia in CKD subjects are critical. | [
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
263890 | Between Direct and Indirect Discourse: Shifting Perspective in Blended Discourse | A fundamental feature of language is that it allows us to reproduce what others have said. It is traditionally assumed that there
are two ways of doing this: direct discourse, where you preserve the original speech act verbatim, and indirect discourse,
where you paraphrase it in your own words. In accordance with this dichotomy, linguists have posited a number of universal
characteristics to distinguish the two modes. At the same time, we are seeing more and more examples that seem to fall
somewhere in between. I reject the direct indirect distinction and replace it with a new paradigm of blended discourse.
Combining insights from philosophy and linguistics, my framework has only one kind of speech reporting, in which a speaker
always attempts to convey the content of the reported words from her own perspective, but can quote certain parts verbatim,
thereby effectively switching to the reported perspective.
To explain why some languages are shiftier than others, I hypothesize that a greater distance from face-to-face
communication, with the possibility of extra- and paralinguistic perspective marking, necessitated the introduction of
an artificial direct indirect separation. I test this hypothesis by investigating languages that are closely tied to direct
communication: Dutch child language, as recent studies hint at a very late acquisition of the direct indirect distinction; Dutch
Sign Language, which has a special role shift marker that bears a striking resemblance to the quotational shift of blended
discourse; and Ancient Greek, where philologists have long been observing perspective shifts.
In sum, my research combines a new philosophical insight on the nature of reported speech with formal semantic rigor and
linguistic data from child language experiments, native signers, and Greek philology. | [
"Texts and Concepts",
"The Human Mind and Its Complexity"
]
|
10.1145/3197517.3201376 | Computational Design Of Nanostructural Color For Additive Manufacturing | Additive manufacturing has recently seen drastic improvements in resolution, making it now possible to fabricate features at scales of hundreds or even dozens of nanometers, which previously required very expensive lithographic methods. As a result, additive manufacturing now seems poised for optical applications, including those relevant to computer graphics, such as material design, as well as display and imaging applications. In this work, we explore the use of additive manufacturing for generating structural colors, where the structures are designed using a fabrication-aware optimization process. This requires a combination of full-wave simulation, a feasible parameterization of the design space, and a tailored optimization procedure. Many of these components should be re-usable for the design of other optical structures at this scale. We show initial results of material samples fabricated based on our designs. While these suffer from the prototype character of state-of-the-art fabrication hardware, we believe they clearly demonstrate the potential of additive nanofabrication for structural colors and other graphics applications. | [
"Condensed Matter Physics",
"Computer Science and Informatics",
"Materials Engineering"
]
|
10.1016/j.chemgeo.2018.03.030 | The stable strontium isotopic composition of ocean island basalts, mid-ocean ridge basalts, and komatiites | The radiogenic 87Rb-87Sr system has been widely applied to the study of geological and planetary processes. In contrast, the stable Sr isotopic composition of the bulk silicate Earth (BSE) and the effects of igneous differentiation on stable Sr isotopes are not well-established. Here we report the stable Sr isotope (88Sr/86Sr, reported as δ88/86Sr, in parts per mil relative to NIST SRM 987) compositions for ocean islands basalts (OIB), mid-ocean ridge basalts (MORB) and komatiites from a variety of locations. Stable Sr isotopes display limited fractionation in a OIB sample suite from the Kilauea Iki lava lake suggesting that igneous processes have limited effect on stable Sr isotope fractionation (±0. 12‰ over 20% MgO variation; 2sd). In addition, OIB (δ88/86Sr = 0. 16–0. 46‰; average 0. 28 ± 0. 17‰), MORB (δ88/86Sr = 0. 27–0. 34‰; average 0. 31 ± 0. 05‰) and komatiites (δ88/86Sr = 0. 20–0. 97‰; average 0. 41 ± 0. 16‰) from global localities exhibit broadly similar Sr stable isotopic compositions. Heavy stable Sr isotope compositions (δ88/86Sr > 0. 5‰) in some Barberton Greenstone belt komatiites may reflect Archean seawater alteration or metamorphic processes and preferential removal of the lighter isotopes of Sr. To first order, the similarity among OIBs from three different ocean basins suggests homogeneity of stable Sr isotopes in the mantle. Earth's mantle stable Sr isotopic composition is established from the data on OIB, MORB and komatiites to be δ88/86Sr = 0. 30 ± 0. 02‰ (2sd). The BSE δ88/86Sr value is identical, within uncertainties, to the composition of carbonaceous chondrites (δ88/86Sr = 0. 29 ± 0. 06‰; 2sd) measured in this study. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
10.1021/acsami.6b02530 | Graphene-Based Bionic Composites with Multifunctional and Repairing Properties | In this work, a novel bionic composite inspired by the concept of yeast fermentation has been proposed. It was observed that the addition of graphene nanoplatelets during the fermentation of extract of Saccharomyces cerevisiae fungi allows coupling of the graphene sheets to the yeast cell wall. This process resulted in the formation of a composite film with improved mechanical and electrical properties along with the capability of converting the light stimulus in the electrical signal. The mechanical properties of the prepared composites, namely, the fracture strength and Young's modulus, were studied via numerical simulations and are related to the properties of the constituent phases via rules of mixture. Finally, it was observed that graphene nanoplatelets, added to the nutrient broth, were able to reassemble onto the stressed cell surface and repair the surface cracking, partially restoring the pristine electrical and mechanical properties. The method reported here may find potential application in the development of self-healable bioelectronic devices and microorganism-based strain and chemical biosensors. (Figure Presented). | [
"Condensed Matter Physics",
"Materials Engineering",
"Biotechnology and Biosystems Engineering"
]
|
W2988039250 | Ozone pollution over China and India: seasonality and sources | Abstract. A regional fully coupled meteorology–chemistry model, Weather Research and Forecasting model with Chemistry (WRF-Chem), was employed to study the seasonality of ozone (O3) pollution and its sources in both China and India. Observations and model results suggest that O3 in the North China Plain (NCP), Yangtze River Delta (YRD), Pearl River Delta (PRD), and India exhibit distinctive seasonal features, which are linked to the influence of summer monsoons. Through a factor separation approach, we examined the sensitivity of O3 to individual anthropogenic, biogenic, and biomass burning emissions. We found that summer O3 formation in China is more sensitive to industrial and biogenic sources than to other source sectors, while the transportation and biogenic sources are more important in all seasons for India. Tagged simulations suggest that local sources play an important role in the formation of the summer O3 peak in the NCP, but sources from Northwest China should not be neglected to control summer O3 in the NCP. For the YRD region, prevailing winds and cleaner air from the ocean in summer lead to reduced transport from polluted regions, and the major source region in addition to local sources is Southeast China. For the PRD region, the upwind region is replaced by contributions from polluted PRD as autumn approaches, leading to an autumn peak. The major upwind regions in autumn for the PRD are YRD (11 %) and Southeast China (10 %). For India, sources in North India are more important than sources in the south. These analyses emphasize the relative importance of source sectors and regions as they change with seasons, providing important implications for O3 control strategies. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
10.1177/1477878518756565 | Meeting Our Standards For Educational Justice Doing Our Best With The Evidence | The United States considers educating all students to a threshold of adequate outcomes to be a central goal of educational justice. The No Child Left Behind Act introduced evidence-based policy and accountability protocols to ensure that all students receive an education that enables them to meet adequacy standards. Unfortunately, evidence-based policy has been less effective than expected. This article pinpoints under-examined methodological problems and suggests a more effective way to incorporate educational research findings into local evidence-based policy decisions. It identifies some things educators need to know and do to determine whether available interventions can play the right casual role in their setting to produce desired effects. It examines the value and limits of educational research, especially randomized controlled trials, for this task. | [
"The Social World and Its Interactions"
]
|
623790 | Microvehicle for stand-alone and shared mobility - leonardo | The objectives of LEONARDO are:
1) to develop a new microvehicle based on the smart fusion of the concepts of monowheel and scooter. The monowheel and the scooter have the best characteristics to be used as a means of daily transport and to fully exploit the intermodality. The new microvehicle will take the best features of these two vehicles and eliminate the disadvantages, obtaining a silent, clean, energy efficient and safe vehicle, as well as attractive and affordable to the public so that the barriers for adopting it are minimized. The development includes a) the consolidation of already outlined conpects, through analysis of functionality and comparison with existing vehicles, on the basis of an extensive analysis of user's needs and safety and regulamentary aspects b) structural and electrical / electronic design c) in-house testing
2) to do an extensive demonstration and re-design activity. The vehicle will be tested in a real environment in 4 European cities: Rome, Eilat and 2 others that will be identified with a tender. In these demonstration tests, a fleet of vehicle will be tested for free by hundreds of users, on a rotating basis. Each vehicle can be used in stand alone mode or in battery sharing mode, through a system already developed by UNIFI, made available for the project. Operating data will be automatically collected through a platform and users will be asked to give feedback weekly. The pilot in Rome will start with 50 vehicles and will be used for a revision and re-design process, to arrive up to a TRL 7. Afterwards, the other pilots will start, in sequence, for 3 months in each city, in which 100 vehicles will be tested. These tests will be used to refine the vehicle up to the TRL8-9 and to do a physical demonstration of the technical and economic feasibility. During the pilots, pre-orders will be accepted. A detailed exploitation strategy and a draft business plan for the vehicle will be draft with the data collected. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
W4280600642 | Chronic treatment with juçara (Euterpe edulis) fruit pulp produces antihypertensive effect and improve on baroreflex sensitivity in Spontaneous Hypertensive Rats (SHR) | Background: Juçara açaí is a Brazilian berry with high anthocyanidin content and high antioxidant properties. A correlation between oxidative stress, hypertension and baroreflex impairment is known, however, no previous studies investigate the effect of juçara fruit pulp on hypertension. Aim: The aim of this study was to investigate antihypertensive effect of juçara (Euterpe edulis) fruit pulp in SHR animals, its antioxidant capacity and influence on baroreflex sensitivity. Methods: Chemical profile was obtained by ESI(-)-FT-ICR-MS. For biological analysis, male SHR were separated into groups: control (S), which received water; captopril (SC), which received captopril (30 mg/kg), and juçara (SJ), which received juçara pulp (4.4mL/kg). Treatments were daily performed by gavage and remained for 8 weeks. Baroreflex evaluation was made by in bolus injection of phenylephrine and sodium nitroprusside, after the analysis the heart was frozen (-80ºC) for biomolecular evaluations (AOPP, TBARS, SOD and catalase activity and protein expression). Results: The treatments promoted decrease in arterial pressure (S: 163.3±2.2; SC: 154.0±0.6; SJ: 149.0±3.8 mmHg) and improved the baroreflex sensitivity after nitroprusside activation. In addition, it promoted a decrease in AOPP and an increase in the activity of antioxidant enzymes. However, no changes were observed in protein expression. Conclusion: It was shown that juçara can promote cardiovascular benefits and its consume should be stimulated for prevention of hypertension. | [
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W2000910899 | Use of multi-parameter distributions for offshore wind speed modeling: The Johnson SB distribution | Abstract Weibull distribution is widely suggested for modeling the behavior of offshore wind speeds. However, it has been often proved to be inadequate, while its indiscriminate use is not justified. Thus, in order to minimize estimation errors in offshore wind energy, it is necessary to select the most appropriate distribution for the wind climate description of a specific area. In this context, the performance of several probability distributions for offshore wind speed modeling, using long-term time series from 11 buoys in Eastern Mediterranean Sea (Greek waters) and 8 buoys in Western Mediterranean Sea (Spanish coastal waters) will be assessed for the first time here. We focus on the efficiency of three bounded multi-parameter distributions: Wakeby and Kappa, that have performed very well in completely different areas of the US coasts, Atlantic and Pacific Oceans, and Johnson S B distribution, which is introduced here for the first time. It is shown that Johnson S B , Kappa and Wakeby distributions accurately describe the empirical distribution of offshore wind speed; they have better adaptability than the 3-parameter Weibull distribution and qualify as reliable and prominent candidates for the assessment of offshore wind speed in any sea area. Moreover, Johnson S B is the only distribution that suits very well for all examined cases, providing consistently fair fits with respect to all goodness-of-fit tests applied. Alternative criteria, such as the performance of the examined probability models in terms of wind power density and average wind turbine power, have also been used for evaluating the fitted wind speed distributions. In this case the results proved to be different. | [
"Earth System Science",
"Mathematics",
"Products and Processes Engineering"
]
|
10.1016/j.measurement.2010.08.001 | An unambiguous expression method of the surface texture | The current specification and verification of surface texture in international standards are considered to be too theoretical, complex and over-elaborate for industry. A functional approach that completely expresses the complicated surface texture knowledge for designers and engineers is often nonexistent on the shop floor. Based on Geometrical Product Specification (GPS) philosophy, this paper proposes an unambiguous expression schema of surface texture. The surface texture knowledge in design, manufacture and measurement is based on the general GPS matrix and structured by a categorical object model. Explicit specification and verification processes and the mapping between them are presented. The ultimate goal is to improve the collaboration and bridge the knowledge gap between design, manufacture and measurement of surface texture to reduce product development lead time and improve product quality and performance. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
10.1016/j.molmet.2016.01.008 | Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance | Objective: Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i. e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods: Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results: We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0. 7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging ("browning") of inguinal white adipose tissue (iWAT). Conclusions: We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. | [
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.5194/acp-19-5111-2019 | Classification of Arctic multilayer clouds using radiosonde and radar data in Svalbard | . Multilayer clouds (MLCs) occur more often in the Arctic than globally. In this study we present the results of a detection algorithm applied to radiosonde and radar data from an 1-year time period in Ny-Ålesund, Svalbard. Multilayer cloud occurrence is found on 29 % of the investigated days. These multilayer cloud cases are further analysed regarding the possibility of ice crystal seeding, meaning that an ice crystal can survive sublimation in a subsaturated layer between two cloud layers when falling through this layer. For this we analyse profiles of relative humidity with respect to ice to identify super- and subsaturated air layers. Then the sublimation of an ice crystal of an assumed initial size of r=400 µm on its way through the subsaturated layer is calculated. If the ice crystal still exists when reaching a lower supersaturated layer, ice crystal seeding can potentially take place. Seeding cases are found often, in 23 % of the investigated days (100 % includes all days, as well as non-cloudy days). The identification of seeding cases is limited by the radar signal inside the subsaturated layer. Clearly separated multilayer clouds, defined by a clear interstice in the radar image, do not interact through seeding (9 % of the investigated days). There are various deviations between the relative humidity profiles and the radar images, e. g. due to the lack of ice-nucleating particles (INPs) and cloud condensation nuclei (CCN). Additionally, horizontal wind drift of the radiosonde and time restriction when comparing radiosonde and radar data cause further deviations. In order to account for some of these deviations, an evaluation by manual visual inspection is done for the non-seeding cases. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
10.3390/e15114648 | From observable behaviors to structures of interaction in binary games of strategic complements | Consider a setting in which agents can take one of two ordered actions and in which the incentive to take the high action increases in the number of other agents taking it. Furthermore, assume that we do not know anything else about the game being played. What can we say about the details of the interaction between actions and incentives when we observe a set or a subset of all possible equilibria? In this paper, we study this question by exploring three nested classes of games: (a) binary games of strategic complements; (b) games in (a) that admit a network representation; and (c) games in (b) in which the network is complete. Our main results are the following: It has long been established in the literature that the set of pure strategy Nash equilibria of any binary game of strategic complements among a set, N, of agents can be seen as a lattice on the set of all subsets of N under the partial order defined by the set inclusion relation (⊆). If the game happens to be strict in the sense that agents are never indifferent among outcomes (games in (a)), then the resulting lattice of equilibria satisfies a straightforward sparseness condition. (1) We show that, in fact, for each such lattice, L, there is a game in (a), such that its set of equilibria is L (we say that such a game expresses L); (2) We show that there exists a game in (b), whose set of equilibria contains a given collection, C, of subsets of N, if and only C satisfies the sparseness condition, and the smallest game in (a) expressing C is trade robust; (3) We show that there exists a game on the complete graph (games in (c)), whose set of equilibria coincides with some collection, C, if and only if C is a chain satisfying the sparseness condition. | [
"Mathematics",
"Computer Science and Informatics"
]
|
10.1016/j.tics.2017.12.001 | Forecasting Faces in the Cortex: Comment on ‘High-Level Prediction Signals in a Low-Level Area of the Macaque Face-Processing Hierarchy’, by Schwiedrzik and Freiwald, Neuron (2017) | Although theories of predictive coding in the brain abound, we lack key pieces of neuronal data to support these theories. Recently, Schwiedrzik and Freiwald found neurophysiological evidence for predictive codes throughout the face-processing hierarchy in macaque cortex. We highlight how these data enhance our knowledge of cortical information processing, and the impact of this more broadly. | [
"Neuroscience and Disorders of the Nervous System"
]
|
10.1080/00268976.2013.788743 | Precision measurement of the ionisation energy of the 3dσ GK state of H<inf>2</inf> | The frequency of the transition between the 3dσ G K 1Σg+ (v = 1, N = 1) state of H 2 and the n = 56p ( N = 1, S = 0) Rydberg state belonging to a series converging to the X+2Σg+ (v+ = 0, N+ = 1) ground state of ortho H2+ has been measured with an accuracy of 1. 2 MHz using a narrow-band pulsed near-infrared (NIR) laser. Systematic errors originating from ac and dc Stark shifts, from pressure shifts and from the frequency shift and chirp accompanying the generation of the NIR laser pulses were quantified. By combining this frequency with the binding energy of the 56p (N = 1, S = 0) Rydberg state, the ionisation energy of the G K 1Σg+ (v = 1, N = 1) state of ortho H2 was determined to be 379855188. 3(12) MHz [12670. 60522(4) cm-1]. This new result represents the first step towards the determination of the ionisation and dissociation energies of molecular hydrogen at a ν/Δν level of accuracy beyond 10 10. Using the current value of the ionisation energy of ortho H 2 [124357. 23797(36) cm-1, from Liu et al. [J. Chem. Phys. 130, 174306 (2009)] and the frequency interval between the N = 1 and N = 0 rotational levels of the X (v = 0) ground state of H2 [118. 48684(10) cm-1, from Jennings et al. [J. Mol. Spectrosc. 126, 19 (1987)], the term value of the G K 1Σg+ (v = 1, N = 1) state was determined to be 111805. 1196(4) cm-1. | [
"Fundamental Constituents of Matter",
"Physical and Analytical Chemical Sciences"
]
|
10.1093/cvr/cvy005 | New models to study vascular mural cell embryonic origin: Implications in vascular diseases | A key question in vascular biology is how the diversity of origin of vascular mural cells, namely smooth muscle cells (SMCs) and pericytes influences vessel properties, in particular the regional propensity to vascular diseases. This review therefore first describes the role and regulation of mural cells during vascular formation, with a focus on embryonic origin. We then consider the evidence that connects heterogeneities in SMC and pericyte origins with disease. Since this idea has major implications for understanding and modelling human disease, then there is a pressing need for new model systems to investigate mural cell development and the consequences of heterogeneity. Recent advances arising from in vitro strategies for deriving mural cells from human pluripotent stem cells as well as from the zebrafish model will be discussed and the medical relevance of these discoveries will be highlighted. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W1485528038 | Indonesian Political Islam: Capitalist Development and the Legacies of the Cold War | This article explores the genesis of Indonesian political Islam and its interactions with the nationalist secular state in the immediate post-colonial era while examining some of the origins of the ‘radical’ stream that has garnered much attention in the current post-authoritarian period. It puts forward the idea that, rather than an outcome of Indonesian democratisation, this stream was in fact the product of authoritarian New Order rule. The article also considers some parallels in the trajectories of political Islam more generally in Indonesia, the Middle East and North Africa, especially as a kind of populist response to the tensions and contradictions of global capitalism. It addresses the city of Surakarta (Solo) as a case study and highlights the importance of Cold War politics in moulding political Islam in Indonesia and elsewhere. The approach emphasises historical and sociological factors shaping political Islam that have tended to be relegated to the background in prevalent security-oriented analyses concerned with issues of terrorism and violence. | [
"The Study of the Human Past",
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.1002/2017JG003833 | Temperature Dependence Of Apparent Respiratory Quotients And Oxygen Penetration Depth In Contrasting Lake Sediments | Lake sediments constitute an important compartment in the carbon cycle of lakes, by burying carbon over geological timescales and by production and emission of greenhouse gases. The degradation of . . . | [
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
]
|
10.1038/s41578-019-0125-0 | Heterogeneity at multiple length scales in halide perovskite semiconductors | Materials with highly crystalline lattice structures and low defect concentrations have classically been considered essential for high-performance optoelectronic devices. However, the emergence of high-efficiency devices based on halide perovskites is provoking researchers to rethink this traditional picture, as the heterogeneity in several properties within these materials occurs on a series of length scales. Perovskites are typically fabricated crudely through simple processing techniques, which leads to large local fluctuations in defect density, lattice structure, chemistry and bandgap that appear on short length scales (<100 nm) and across long ranges (>10 μm). Despite these variable and complex non-uniformities, perovskites maintain exceptional device efficiencies and are, as of 2018, the best-performing polycrystalline thin-film solar cell material. In this Review, we highlight the multiple layers of heterogeneity ascertained using high-spatial-resolution methods that provide access to the relevant length scales. We discuss the impact that the optoelectronic variations have on halide perovskite devices, including the prospect that it is this very disorder that leads to their remarkable power-conversion efficiencies. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
US 2010/0042027 W | SEMICONDUCTOR-ON-INSULATOR WITH BACK SIDE SUPPORT LAYER | Embodiments of the present invention provide for the provisioning of efficient support to semiconductor-on-insulator (SOI) structures. Embodiments of the present invention may additionally provide for SOI structures with improved heat dissipation performance while preserving the beneficial electrical device characteristics that accompany SOI architectures. In one embodiment, an integrated circuit is disclosed. The integrated circuit comprises a silicon-on-insulator die from a silicon-on-insulator wafer. The silicon on insulator die comprises an active layer, an insulator layer, a substrate, and a strengthening layer. The substrate consists of an excavated substrate region, and a support region, the support region is in contact with the insulator layer. The support region and the strengthening layer are configured to act in combination to provide a majority of a required stabilizing force to the silicon-on-insulator die when it is singulated from the silicon-on-insulator wafer. | [
"Systems and Communication Engineering",
"Materials Engineering"
]
|
101001016 | Photoactivatable Drug Releasing Implants | This proposal introduces a next-generation platform for next generation optimally personalised drug therapy: on-demand drug releasing implants triggered and controlled by blue/UV light. The technology is based on novel light generation pathways and a light-sensitive nanocellulose drug reservoir.
A formidable physiological barrier for light-triggered drug release has been the inability to use high-energy blue/UV light as the triggering signal. This is because the penetration depth of light drops to from a few cm to under 100 micrometers when moving from near-infrared to UV light, making deeper targets within tissues accessible only to red light. However, red light, with its intrinsically lower energy, has limited value in photochemical reactions because the photocleavage of covalent bonds typically requires UV-light. This is why many groups are looking at e.g. red-to-blue photon upconversion strategies. The major objective in PADRE is to circumvent the issue of unavailable blue light in implants through local light generation. Having access to light with higher energy will enable a much wider chemical toolbox, including photocleavable linkers.
I will use blue/UV light to trigger and precisely control drug release. The approach creates an unconventional way to modulate the release profiles without unwanted drug leakage. The light will be generated through either 1) photon upconversion, or 2) integrated light sources. With the first approach, I will pioneer efficient red-to-blue/UV triplet-triplet annihilation upconversion in a hydrogel environment, while in the second approach I will generate light by a co-implanted light source. Both approaches are feasible according to my preliminary results on efficient triplet-triplet annihilation upconversion and photoresponsive liposomes and will be demonstrated in a working implant prototype. The core breakthrough of PADRE will be a viable solution to employ blue excitation in precisely-tailored drug-releasing implants. | [
"Materials Engineering",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W1716941828 | Antidepressant activated biochemical pathways and biomarker candidates | Most of the commonly used antidepressants block monoamine reuptake transporters to enhance serotonergic or noradrenergic neurotransmission. Effects besides or downstream of increased monoaminergic neurotransmission are poorly understood and yet presumably important for the drugs’ mode of action. In my PhD thesis I employed proteomics and metabolomics technologies combined with in silico analyses and identified cellular pathways affected by antidepressant drug treatment. DBA/2 mice were treated with paroxetine as a representative Selective Serotonin Reuptake Inhibitor (SSRI). Hippocampal protein levels were compared between chronic paroxetine- and vehicle-treated animals using in vivo 15N metabolic labeling combined with mass spectrometry. I also studied chronic changes in the hippocampus using unbiased metabolite profiling and the time course of metabolic changes with the help of a targeted polar metabolomics profiling platform. I identified profound alterations related to hippocampal energy metabolism. Glycolytic metabolite levels acutely increased while Krebs cycle metabolite levels decreased upon chronic treatment. Changes in energy metabolism were influenced by altered glycogen metabolism rather than by altered glycolytic or Krebs cycle enzyme levels. Increased energy levels were reflected by an increased ATP/ADP ratio and by increased ratios of high-to-low energy purines and pyrimidines. Paralleling the shift towards aerobic glycolysis upon paroxetine treatment I identified decreased levels of Krebs cycle and oxidative phosphorylation enzyme levels upon the antidepressant-like 15N isotope effect in high-anxiety behavior mice. In the course of my analyses I also identified GABA, galactose-6-phosphate and leucine as biomarker candidates for the assessment of chronic paroxetine treatment effects in the periphery and myo-inositol as biomarker candidate for an early assessment of chronic treatment effects. The identified antidepressant drug treatment affected molecular pathways and novel SSRI modes of action warrant consideration in antidepressant drug development efforts. | [
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1002/admi.201300051 | Nanometer-Scale Precision Tuning of 3D Photonic Crystals Made Possible Using Polyelectrolytes with Controlled Short Chain Length and Narrow Polydispersity | Nanometer-scale tuning of the optical properties of prefabricated photonic crystals is achieved via layer-by-layer assembly of polyelectrolytes in the interstitial spaces of the photonic lattice. The key to the approach is using polyelectrolytes with controlled short chain lengths. This ensures they do not block the air voids, thereby maintaining uniform coating and thus precise and reproducible optical tuning. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1039/C8NR07164K | Evaluation Of 3D Gold Nanodendrite Layers Obtained By Templated Galvanic Displacement Reactions For Sers Sensing And Heterogeneous Catalysis | Dense layers of overlapping three-dimensional (3D) gold nanodendrites characterized by high specific surfaces as well as by abundance of sharp edges and vertices creating high densities of SERS hotspots are promising substrates for SERS-based sensing and catalysis. We have evaluated to what extent structural features of 3D gold nanodendrite layers can be optimized by the initiation of 3D gold nanodendrite growth at gold particles rationally positioned on silicon wafers. For this purpose, galvanic displacement reactions yielding 3D gold nanodendrites were guided by hexagonal arrays of parent gold particles with a lattice constant of 1. 5 micrometers obtained by solid-state dewetting of gold on topographically patterned silicon wafers. Initiation of the growth of dendritic features at edges of the gold particles resulted in the formation of 3D gold nanodendrites while limitation of dendritic growth to the substrate plane was prevented. The regular arrangement of the parent gold particles supported the formation of dense layers of overlapping 3D gold nanodendrites that were sufficiently homogeneous within the resolution limits of Raman microscopes. Consequently, SERS mapping experiments revealed a reasonable degree of uniformity. The proposed preparation algorithm comprises only bottom-up process steps that can be carried out without use of costly instrumentation. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Synthetic Chemistry and Materials",
"Materials Engineering"
]
|
10.1093/infdis/jis273 | A new class of synthetic peptide inhibitors blocks attachment and entry of human pathogenic viruses | Many enveloped viruses, including herpes viruses, hepatitis B virus (HBV), and hepatitis C virus (HCV), and human immunodeficiency virus (HIV), are among the most important human pathogens and are often responsible for coinfections involving ≥2 types of viruses. However, therapies that are effective against multiple virus classes are rare. Here we present a new class of synthetic anti-lipopolysaccharide peptides (SALPs) that bind to heparan sulfate moieties on the cell surface and inhibit infection with a variety of enveloped viruses. We demonstrate that SALPs inhibit entry of human immunodeficiency virus type 1 (HIV-1), herpes simplex virus (HSV) 1 and 2, HBV, and HCV to their respective host cells. Despite their high antiviral efficiency, SALPs were well tolerated, and neither toxicity nor measurable inhibitor-induced adverse effects were observed. Since these broad-spectrum antiviral peptides target a host cell rather than a viral component, they may also be useful for suppression of viruses that are resistant to antiviral drugs. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1007/JHEP02(2016)039 | Flux Formulation Of Dft On Group Manifolds And Generalized Scherk Schwarz Compactifications | A flux formulation of Double Field Theory on group manifold is derived and applied to study generalized Scherk-Schwarz compactifications, which give rise to a bosonic subsector of half-maximal, electrically gauged supergravities. In contrast to the flux formulation of original DFT, the covariant fluxes split into a fluctuation and a background part. The latter is connected to a $2D$-dimensional, pseudo Riemannian manifold, which is isomorphic to a Lie group embedded into O($D,D$). All fields and parameters of generalized diffeomorphisms are supported on this manifold, whose metric is spanned by the background vielbein $E_A{}^I \in$ GL($2D$). This vielbein takes the role of the twist in conventional generalized Scherk-Schwarz compactifications. By doing so, it solves the long standing problem of constructing an appropriate twist for each solution of the embedding tensor. Using the geometric structure, absent in original DFT, $E_A{}^I$ is identified with the left invariant Maurer-Cartan form on the group manifold, in the same way as it is done in geometric Scherk-Schwarz reductions. We show in detail how the Maurer-Cartan form for semisimple and solvable Lie groups is constructed starting from the Lie algebra. For all compact embeddings in O($3,3$), we calculate $E_A{}^I$. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
W1988455956 | Making morality: sustainable architecture and the pragmatic imagination | Environmental ethics as a discipline has directed little attention towards the built environment and even less to the process of building design. Conversely, within the professional context of architectural practice, questions of ethics and morality have hardly figured within a rapidly developing discourse of sustainability in which environmental values have tended to be downplayed in the pursuit of quantitative models of environmental innovation. The philosophy of pragmatism potentially provides a useful analytical and moral framework that links the environmental ethics of sustainability to the design, construction, and use of buildings. Pragmatism's embrace of contextual pluralism, its emphasis on experience and practice, and its high regard for the political worth of the community move the discussion away from a narrow focus on predefined and universal codes, whether ethical or technical. Sustainable design should be understood as a ‘co-evolutionary’ ethical practice, a socio-technical process that eng... | [
"Products and Processes Engineering",
"Human Mobility, Environment, and Space"
]
|
10.1093/bioinformatics/btv660 | Annotation of rule-based models with formal semantics to enable creation, analysis, reuse and visualization | Abstract
Motivation: Biological systems are complex and challenging to model and therefore model reuse is highly desirable. To promote model reuse, models should include both information about the specifics of simulations and the underlying biology in the form of metadata. The availability of computationally tractable metadata is especially important for the effective automated interpretation and processing of models. Metadata are typically represented as machine-readable annotations which enhance programmatic access to information about models. Rule-based languages have emerged as a modelling framework to represent the complexity of biological systems. Annotation approaches have been widely used for reaction-based formalisms such as SBML. However, rule-based languages still lack a rich annotation framework to add semantic information, such as machine-readable descriptions, to the components of a model. Results: We present an annotation framework and guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages. We adapt widely adopted annotation approaches to rule-based models. We initially propose a syntax to store machine-readable annotations and describe a mapping between rule-based modelling entities, such as agents and rules, and their annotations. We then describe an ontology to both annotate these models and capture the information contained therein, and demonstrate annotating these models using examples. Finally, we present a proof of concept tool for extracting annotations from a model that can be queried and analyzed in a uniform way. The uniform representation of the annotations can be used to facilitate the creation, analysis, reuse and visualization of rule-based models. Although examples are given, using specific implementations the proposed techniques can be applied to rule-based models in general. Availability and implementation: The annotation ontology for rule-based models can be found at http://purl. org/rbm/rbmo. The krdf tool and associated executable examples are available at http://purl. org/rbm/rbmo/krdf. Contact: anil. wipat@newcastle. ac. uk or vdanos@inf. ed. ac. uk | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Computer Science and Informatics"
]
|
W66701934 | Necroptotic Death Of RIPK1-Deficient HSC Compromises Hematopoiesis | Abstract Introduction Cell death can be triggered by many stimuli leading to apoptosis, pyroptosis (Caspase-1-dependent cell death) or necroptosis (Receptor-interacting serine/threonine-protein kinase (RIPK)-1/RIPK3-dependent cell death). RIPK1 is engaged by TNFR or Fas/CD95 ligation, and can induce NF-κB activation and cell death. FADD and Caspase-8 modulate RIPK1 and RIPK3 activity to prevent inappropriate induction of necroptosis (Oberst et al., Nature 2011, 471: 363-367; Zhang et al., Nature 2011, 471: 373-376). Modulation of necroptosis by small molecule inhibitors of RIPK1 has emerged as an exciting approach to intervene in inflammatory disease, ischemia reperfusion injury, pancreatitis and in mouse models of sepsis (He et al., Cell 2009, 137: 1100-1111; McNeal et al., Shock 2011, 35: 499-505; Oerlemans et al., Basic Res Cardiol 2012, 107: 270; Lukens et al., Nature 2013, 498: 224-227). However, RIPK1-deficient neonates die at birth and exhibit inflammatory disease and anemia, suggesting that inhibitors of RIPK1 may alter hematopoiesis. We have therefore investigated the hematological consequences of RIPK1 deficiency. Methods Fetal liver chimeras and competitive transplants were generated using E13.5 Ripk1-/-, Ripk3-/-and Ripk1-/-Ripk3-/- fetal liver cells. Serial transplants were established using 106 fetal liver cells for primary transplants and 0.2-5 x 106 bone marrow cells for secondary transplants. The survival of recipient mice and frequency of donor, competitor and recipient cells was assessed by flow cytometry up to 6 months post transplantation. The frequency of hematopoietic progenitor cells was assessed using in vitro clonal culture assays of E13.5-E18.5 fetal liver cells stimulated with SCF+IL-3+Epo in the presence or absence of TNFα or FasL. The contribution of TNFα and FasL to hematopoiesis was examined using TNFα neutralizing antibody in lethally-irradiated recipients of Ripk1-/- cells or by engrafting Ripk1-/- cells into lethally-irradiated Tnfa-/-Faslgld/gldrecipient mice. Results Ripk1 -/- fetal liver cells fail to engraft in lethally-irradiated recipients, with defects evident in lymphoid and myeloid lineages in the bone marrow, peripheral blood and spleen between 4 and 26 weeks post-transplant. In competitive fetal liver transplant experiments, Ripk1-/- hematopoietic stem and progenitor cells failed to compete with wild-type counterparts, indicating a cell-intrinsic defect in hematopoietic progenitor cells that cannot be attributed to the inflammatory disease evident in Ripk1-/- embryos. Ripk1-/- myeloid progenitor cells were sensitive to death induced by TNFα or FasL stimulation. Only minor abnormalities in hematopoiesis were detected when Ripk1-/- fetal liver cells were transplanted into lethally-irradiated Tnfa-/-Faslgld/gld recipient mice, or when lethally-irradiated wild-type recipient mice receiving Ripk1-/- fetal liver cells were treated with a TNFα neutralizing antibody, indicating key roles for TNFα and FasL during engraftment. A compound deficiency in RIPK3 rescued the reconstitution defects seen in Ripk1-/- cells suggesting that RIPK1-deficient hematopoietic cells undergo RIPK3-dependent necroptotic death. A residual defect in Ripk1-/-Ripk3-/-T lymphopoiesis suggests that RIPK1 deficiency induces other forms of cell death or that RIPK1 is required for other essential signaling pathways such as NF-κB signaling. Conclusion These data demonstrate essential roles for RIPK1 in hematopoiesis at steady state. Our results indicate that small molecule RIPK1 inhibitors should be used with caution in the clinic to avoid activation of RIPK3-dependent cell death pathways leading to cytopenia, immunosuppression and bone marrow failure. Finally, this work highlights that studies using RIPK1-deficient cells to study the roles for RIPK1 in inflammatory disease must draw conclusions with care considering the critical role of RIPK1 in hematopoiesis. Disclosures: No relevant conflicts of interest to declare. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy"
]
|
10.1038/nature16143 | Molecular structures of unbound and transcribing RNA polymerase III | Transcription of genes encoding small structured RNAs such as transfer RNAs, spliceosomal U6 small nuclear RNA and ribosomal 5S RNA is carried out by RNA polymerase III (Pol III), the largest yet structurally least characterized eukaryotic RNA polymerase. Here we present the cryo-electron microscopy structures of the Saccharomyces cerevisiae Pol III elongating complex at 3. 9 Å resolution and the apo Pol III enzyme in two different conformations at 4. 6 and 4. 7 Å resolution, respectively, which allow the building of a 17-subunit atomic model of Pol III. The reconstructions reveal the precise orientation of the C82-C34-C31 heterotrimer in close proximity to the stalk. The C53-C37 heterodimer positions residues involved in transcription termination close to the non-template DNA strand. In the apo Pol III structures, the stalk adopts different orientations coupled with closed and open conformations of the clamp. Our results provide novel insights into Pol III-specific transcription and the adaptation of Pol III towards its small transcriptional targets. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
Q4762611 | TECNOLOGÍA DE POTENCIA FLUIDA S.R.L. | LA INVERSIÓN PREVISTA PARA EL AÑO 2017 ES NECESARIA PARA PODER OFRECER EN EL MERCADO PRODUCTOS CADA VEZ MÁS VERSÁTILES Y ADECUADOS PARA LOS MUCHOS CAMPOS DE APLICACIÓN A LOS QUE SE DIRIGE FPT. CON LA ENTRADA EN FUNCIONAMIENTO DE LA NUEVA MAQUINARIA FPT AUMENTARÁ LA GAMA DE SUS ARTÍCULOS, MEJORARÁ LAS CARACTERÍSTICAS TÉCNICAS DE LOS MISMOS Y, POR LO TANTO, PODRÁ SATISFACER LAS MUCHAS DEMANDAS DEL MERCADO. LA INVERSIÓN TAMBIÉN PERMITE LA REDUCCIÓN DE LOS TIEMPOS DE PRODUCCIÓN, YA QUE CONCENTRA LAS FASES DE TRABAJO EN UNA SOLA MÁQUINA, LO QUE PERMITE MEJORAR LA PRODUCTIVIDAD, LO QUE RESULTA EN UNA REDUCCIÓN DE LOS COSTES. | [
"Products and Processes Engineering"
]
|
617312 | A Single Cell AnaLysis and Sorting Platform based on Lensfree digital imaging techniques applied to Rapid Detection of Cancer | Metastasis is responsible for > 90% of cancer-related deaths. Billions of dollars have been spent trying to cure primary tumors but very little was spent in trying to detect or kill the highly aggressive tumor cells that cause disease spreading. One of the reasons is that single cell studies of rare cells in blood still present a large challenge. Single cell analysis remains tedious with many different instruments and protocols, typically taking a few days of hands-on work. This slows down research, but also hinders the translation to application in future clinical practice. In SCALPEL, we envisage a high-content, high-throughput cell imaging and sorting platform, more compact and easier to use than any existing single cell analyzer. The high content results from lensfree digital imaging of single cells on a high speed CMOS active optical pixel matrix to analyze the morphology of cells. The high throughput results from a highly parallelized fluidic matrix that steers cells at high speed over the CMOS imaging blocks. Lensfree cell sorters can be realized in a cheap and compact platform, as all optomechanical components (lenses, detectors, nozzles,...) are replaced by nanoelectronics, advanced imaging and signal processing technology.
SCALPEL aims to perform a full feasibility study of this concept and will require to investigate the ultimate limits in: 1) maximizing image resolution and sensitivity to single cell morphological features obtained via lensfree holographic imaging; 2) maximizing cell manipulation speed in microfluidic systems via a high degree of parallelization; and 3) digital image signal processing with extremely low latency at reasonable power consumption. If this multidisciplinary complexity can be understood, we will have built the components for different versions of compact cytometers that can be used at hand of pathologist, surgeons, and nurses for improving the individualized follow-up and survival rate of cancer patients. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
757333 | SPD nanostructured magnets with tuneable properties | The decrease of weight and the increase of efficiency of magnetic components are essential for the reduction of CO2-emission and an improvement of their performance. Nanostructuring can dramatically improve the magnetic properties of soft and hard magnetic materials, hence opening up entirely new possibilities for the development of novel magnets. Nanocomposite magnets, for example, have been the focus of research since two decades. One of the remaining key challenges is to synthesize bulk nanostructured magnets of a reasonable size. In this project, this challenge is explicitly addressed and the potential to fabricate bulk nanostructured magnets by severe plastic deformation (SPD) as an innovative processing route is evaluated. The aim of the project is not only to synthesize different nanostructured magnets by SPD, but also to tailor their microstructure to attain the desired magnetic properties. It has been shown by the applicant that the magnetic properties of SPD processed nanocrystalline materials can be modified in wide range by decomposition of metastable solid solutions. By using different immiscible systems, decomposition mechanisms and annealing treatments, unique nanostructures can be obtained and the magnetic properties can be optimized. Through the choice of different magnetic starting materials, such as soft, hard and antiferromagnetic-ferromagnetic powders, different types of hard magnetic nanocomposites will also be obtained. Fine tuning of the microstructure and resulting magnetic properties through adjustments in the composition, SPD processing parameters and annealing treatments is planned. The project systematically addresses the entire process from the synthesis to the in-depth microstructural characterization by electron microscopy and atom probe tomography. In combination with simultaneous measurements of magnetic properties, the newly developed knowledge will be used to improve the performance of SPD processed nanostructured magnets. | [
"Condensed Matter Physics",
"Materials Engineering",
"Synthetic Chemistry and Materials"
]
|
US 57778704 A | Pipeline closing apparatus | A pipeline closing apparatus comprises a lid member attachable to a downstream end portion of a sluice valve, a first control shaft extending through the lid member, a second control shaft extending through the first control shaft, an elastic annular member disposed between pressing plates and provided on inward end regions of the control shafts and elastically deformable to a diameter-increased position by being clamped and pressed, thereby to block between an inner peripheral surface of a branch pipe and the pressing plates, and a retaining device. The retaining device includes engaging link pairs flexing and bulging to a diameter-increased position in response to outward sliding movement of the second control shaft relative to the first control shaft. The apparatus further comprises a reversal preventing device F which, contacts and limits the engaging link pairs and to an outwardly bent position where flexing pivotal portions of the engaging link pairs project radially outward. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
10.1186/s12861-017-0157-x | Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus) - Towards understanding gene function and regulatory evolution in an ecological model system for rapid phenotypic diversification | Background: The Midas cichlid species complex (Amphilophus spp. ) is widely known among evolutionary biologists as a model system for sympatric speciation and adaptive phenotypic divergence within extremely short periods of time (a few hundred generations). The repeated parallel evolution of adaptive phenotypes in this radiation, combined with their near genetic identity, makes them an excellent model for studying phenotypic diversification. While many ecological and evolutionary studies have been performed on Midas cichlids, the molecular basis of specific phenotypes, particularly adaptations, and their underlying coding and cis-regulatory changes have not yet been studied thoroughly. Results: For the first time in any New World cichlid, we use Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus). By adapting existing microinjection protocols, we established an effective protocol for transgenesis in Midas cichlids. Embryos were injected with a Tol2 plasmid construct that drives enhanced green fluorescent protein (eGFP) expression under the control of the ubiquitin promoter. The transgene was successfully integrated into the germline, driving strong ubiquitous expression of eGFP in the first transgenic Midas cichlid line. Additionally, we show transient expression of two further transgenic constructs, ubiquitin::tdTomato and mitfa::eGFP. Transgenesis in Midas cichlids will facilitate further investigation of the genetic basis of species-specific traits, many of which are adaptations. Conclusion: Transgenesis is a versatile tool not only for studying regulatory elements such as promoters and enhancers, but also for testing gene function through overexpression of allelic gene variants. As such, it is an important first step in establishing the Midas cichlid as a powerful model for studying adaptive coding and non-coding changes in an ecological and evolutionary context. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1002/ardp.201500120 | Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma | Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. RNA interference (RNAi) may be a promising treatment of asthma, but so far difficulties regarding the delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells/tissues have limited its clinical application. This review summarizes the cytokines, chemokines, transcription factors, tyrosine kinases, and costimulatory factors reported as targets of siRNA-mediated treatment in experimental asthma. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.4161/auto.28479 | Phosphorylation of NBR1 by GSK3 modulates protein aggregation | The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation. Numerous neurodegenerative and neuromuscular diseases are associated with inappropriate aggregation of ubiquitinated proteins and GSK3 (glycogen synthase kinase 3) activity is involved in several of these proteinopathies. Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation. Indeed, NBR1 phosphorylation decreases protein aggregation induced by puromycin or by the DES/desmin N342D mutant found in desminopathy patients and stabilizes ubiquitinated proteins. Importantly, decrease of protein aggregates is due to an inhibition of their formation and not to their autophagic degradation as confirmed by data on Atg7 knockout mice. The relevance of NBR1 phosphorylation in human pathology was investigated. Analysis of muscle biopsies of sporadic inclusion body myositis (sIBM) patients revealed a strong decrease of NBR1 phosphorylation in muscles of sIBM patients that directly correlated with the severity of protein aggregation. We propose that phosphorylation of NBR1 by GSK3 modulates the formation of protein aggregates and that this regulation mechanism is defective in a human muscle proteinopathy. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing",
"Neuroscience and Disorders of the Nervous System"
]
|
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