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220422 | The role of chromatin in the long-term adaptation of plants to abiotic stress | Abiotic stress is a major threat to global crop yields and this problem is likely to be exacerbated in the future. Therefore, it is very important to engineer crop plants with improved stress tolerance. A large body of research has focussed on the immediate stress responses. However, in nature stress is frequently chronic or recurring, suggesting that temporal dynamics are an important, but under-researched, component of plant stress responses. Indeed, plants can be primed by a stress exposure such that they respond more efficiently to the next stress incident. Such stress priming and memory may be particularly beneficial to plants due to their sessile life style. Typically, the memory of priming lasts for several days after the end of the stress. During the past few years, my group has initiated a molecular analysis of heat stress memory in Arabidopsis thaliana. Heat stress memory is associated with sustained gene induction and transcriptional memory and we have demonstrated that this involves lasting chromatin changes. The underlying molecular mechanisms, however, remain poorly understood. Here, I propose to combine mechanistic dissection of heat stress memory in A. thaliana with concomitant translation of the results into the temperate cereal crop barley. In particular, we will study the following questions: What is the role of chromatin during heat stress memory? How do the transcription factors involved mediate memory-specific outputs? How does nucleosome positioning affect heat stress memory? How do histone modifications during stress memory interact with transcription, chromatin and nuclear organization? Is heat stress memory conserved in temperate cereal species? Can we engineer plants with improved stress memory? Using existing tools and new methodologies, the proposed analyses will yield unprecedented insight into the long-term adaptation of plants to abiotic stress and open up approaches for breeding of stress-tolerant crops. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1016/j.molcel.2017.04.025 | Extending the Host Range of Bacteriophage Particles for DNA Transduction | A major limitation in using bacteriophage-based applications is their narrow host range. Approaches for extending the host range have focused primarily on lytic phages in hosts supporting their propagation rather than approaches for extending the ability of DNA transduction into phage-restrictive hosts. To extend the host range of T7 phage for DNA transduction, we have designed hybrid particles displaying various phage tail/tail fiber proteins. These modular particles were programmed to package and transduce DNA into hosts that restrict T7 phage propagation. We have also developed an innovative generalizable platform that considerably enhances DNA transfer into new hosts by artificially selecting tails that efficiently transduce DNA. In addition, we have demonstrated that the hybrid particles transduce desired DNA into desired hosts. This study thus critically extends and improves the ability of the particles to transduce DNA into novel phage-restrictive hosts, providing a platform for myriad applications that require this ability. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Biotechnology and Biosystems Engineering"
]
|
10.1007/jhep03(2020)154 | Off-shell vs on-shell modelling of top quarks in photon associated production | We present a comparative study of various approaches for modelling of the $$ {e}^{+}{v}_e{\mu}^{-}{\overline{v}}_{\mu }b\overline{b}\gamma $$ e + v e μ − v ¯ μ b b ¯ γ final state in $$ t\overline{t}\gamma $$ t t ¯ γ production at the LHC. Working at the NLO in QCD we compare the fully realistic description of the top quark decay chain with the one provided by the narrow-width-approximation. The former approach comprises all double, single and non-resonant diagrams, interferences, and off-shell effects of the top quarks. The latter incorporates only double resonant contributions and restricts the unstable top quarks to on-shell states. We confirm that for the integrated cross sections the finite top quark width effects are small and of the order of $$ \mathcal{O}\left({\Gamma}_t/{m}_t\right) $$ O Γ t / m t . We show, however, that they are strongly enhanced for more exclusive observables. In addition, we investigate fractions of events where the photon is radiated either in the production or in the decay stage. We find that large fraction of isolated photons comes from radiative decays of top quarks. Based on our findings, selection criteria might be developed to reduce such contributions, that constitute a background for the measurement of the anomalous couplings in the $$ t\overline{t}\upgamma $$ t t ¯ γ vertex. | [
"Fundamental Constituents of Matter"
]
|
interreg_686 | competivity company and innovation | "This project is part of the plan CLIP" : The CIRCUITO project aims to structure a shared cross-border programing to sustain innovation capacities of industries within ALCOTRA’s cooperation space. CIRCUITO allows a real sharing between regional authorities and structures sustaining innovation of strategies to pursue to increase the capacity to product innovation in ALCOTRA’s territory.
CLIP’s plan aims to create conditions for a long-term development of a cross-border system of innovation. The strategy purposed is based on the accessibility of numerical infrastructures systems and data sharing, the access to new innovative services for PMI, and the implementation of new services in the e-health sectors and of the e-mobility. This plan is articulated on three projects, deicated to test and develop innovative services for industries (Circuito), for health sector (E-Santé and silver economy) and for mobility in cross-border era (e-transport). The fourth project “interoperability” needs to furnish in a cross-border manner a sustain for the development of stockage systems and the sharing of datas on both sides of the border, but also for the development of a web cross-border platform dedicated to the distribution of developed services by three other projects. | [
"Computer Science and Informatics",
"Products and Processes Engineering",
"Individuals, Markets and Organisations"
]
|
10.1039/C2NR30431G | Correlative Light Ion Microscopy For Biological Applications | Here we report a new technique, Correlative Light-Ion Microscopy (CLIM), to correlate SEM-like micrographs with fluorescence images. This technique presents significant advantages over conventional methods in enabling topographical and biochemical information to be correlated with nanoscale resolution without destroying the fluorescence signal. We demonstrate the utility of CLIM for a variety of investigations of cell substrate interactions validating its potential to become a routine procedure in biomedical research. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
US 201314424023 A | METHOD OF OPERATING A WIND TURBINE | Method of operating a wind turbine comprising detecting when a first blade substantially approaches the shadow of the tower, and pitching at least one other blade, which is in or approaching a position above the tower, to increase the angle of attack and wind load on said at least one other blade in such a way that an increase of the tilt angle of the rotor is caused. The method further comprises detecting when the first blade is substantially close to leaving the shadow of the tower, and pitching the at least one other blade to decrease the angle of attack and wind load on said at least one other blade in such a way that the previously caused increase of the tilt angle of the rotor is cancelled. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
10.1051/0004-6361/201628913 | Impact Of Flux Distribution On Elementary Heating Events | This work used the COSMA Data Centric system at Durham University, operated by the Institute for Computational Cosmology on behalf of the STFC DiRAC HPC Facility (www. dirac. ac. uk. This equipment was funded by a BIS National E-infrastructure capital grant ST/K00042X/1, STFC capital grant ST/K00087X/1, DiRAC Operations grant ST/K003267/1 and Durham University. DiRAC is part of the National E-Infrastructure. I. D. M was funded by the Science and Technology Facilities Council (UK). The research leading to these results has also received funding from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation programme (grant agreement No. 647214). J. O was funded by the Science and Technology Facilities Council (UK) by Doctoral Grant [ST/K502327/1]. | [
"Universe Sciences",
"Computer Science and Informatics"
]
|
10.1016/j.cub.2014.08.005 | The balance of prickle/spiny-legs isoforms controls the amount of coupling between core and fat PCP systems | Background: The conserved Fat and Core planar cell polarity (PCP) pathways work together to specify tissue-wide orientation of hairs and ridges in the Drosophila wing. Their components form intracellularly polarized complexes at adherens junctions that couple the polarity of adjacent cells and form global patterns. How Fat and Core PCP systems interact is not understood. Some studies suggest that Fat PCP directly orients patterns formed by Core PCP components. Others implicate oriented tissue remodeling in specifying Core PCP patterns. Results: We use genetics, quantitative image analysis, and physical modeling to study Fat and Core PCP interactions during wing development. We show their patterns change during morphogenesis, undergoing phases of coupling and uncoupling that are regulated by antagonistic Core PCP protein isoforms Prickle and Spiny-legs. Evolving patterns of Core PCP are hysteretic: the early Core PCP pattern is modified by tissue flows and then by coupling to Fat PCP, producing sequential patterns that guide hairs and then ridges. Our data quantitatively account for altered hair and ridge polarity patterns in PCP mutants. Premature coupling between Fat and Core PCP explains altered polarity patterns in pk mutants. In other Core PCP mutants, hair polarity patterns are guided directly by Fat PCP. When both systems fail, hairs still align locally and obey signals associated with veins. Conclusions: Temporally regulated coupling between the Fat and Core PCP systems enables a single tissue to develop sequential polarity patterns that orient distinct morphological structures. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1109/TNET.2016.2619721 | Network Coding Schemes For Data Exchange Networks With Arbitrary Transmission Delays | In this paper, we introduce construction techniques for network coding in bidirectional networks with arbitrary transmission delays. These coding schemes reduce the number of transmissions and achieve the optimal rate region in the corresponding broadcast model for both multiple unicast and multicast cases with up to three users, under the equal rate constraint. The coding schemes are presented in two phases; first, coding schemes for line, star and line-star topologies with arbitrary transmission delays are provided and second, any general topology with multiple bidirectional unicast and multicast sessions is shown to be decomposable into these canonical topologies to reduce the number of transmissions. As a result, the coding schemes developed for the line, star, and line-star topologies serve as building blocks for the construction of more general coding schemes for all networks. The proposed schemes are proved to be real time in the sense that they achieve the minimum decoding delay. With a negligible size header, these coding schemes are shown to be applicable to unsynchronized networks, i. e. , networks with arbitrary transmission delays. Finally, we demonstrate the applicability of these schemes by extensive simulations. The implementation of such coding schemes on a wireless network with arbitrary transmission delays can improve performance and power efficiency. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
10.1016/j.bspc.2017.12.007 | Ultrasonic characterization and multiscale analysis for the evaluation of dental implant stability: A sensitivity study | With the aim of surgical success, the evaluation of dental implant long-term stability is an important task for dentists. About that, the complexity of the newly formed bone and the complex boundary conditions at the bone-implant interface induce the main difficulties. In this context, for the quantitative evaluation of primary and secondary stabilities of dental implants, ultrasound based techniques have already been proven to be effective. The microstructure, the mechanical properties and the geometry of the bone-implant system affect the ultrasonic response. The aim of this work is to extract relevant information about primary stability from the complex ultrasonic signal obtained from a probe screwed to the implant. To do this, signal processing based on multiscale analysis has been used. The comparison between experimental and numerical results has been carried out, and a correlation has been observed between the multifractal signature and the stability. Furthermore, a sensitivity study has shown that the variation of certain parameters (i. e. central frequency and trabecular bone density) does not lead to a change in the response. | [
"Condensed Matter Physics",
"Materials Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
Q2045630 | ARREDO IN POROTEX | LA PROPOSTA PROGETTUALE MIRA A STUDIARE E SVILUPPARE UNA INNOVATIVA LINEA DI PRODOTTI DI ARREDO IN POROTEX (MOBILI PER LA CASA E PER L¿UFFICIO, DIVISORI E COMPLEMENTI DI ARREDO) CONFIGURABILI IN MODO DA ESSERE PERSONALIZZATI SECONDO LE SPECIFICHE ESIGENZE DEL CLIENTE, CHE POTRà ESSERE SIA IL CONSUMATORE FINALE, CHE AVRà ACCESSO AL CATALOGO ONLINE, SIA DESIGNERS ED ARCHITETTI DI INTERNI E DI ESTERNI, CHE SI OCCUPANO DI CREARE NUOVI PRODOTTI PER PARTICOLARI CONTESTI (RESIDENZIALI, COMMERCIALI E DIREZIONALI). TALE NUOVA LINEA DI PRODOTTI SARà DOTATA ANCHE DI ILLUMINAZIONE INTEGRATA, COERENTE PER FORMA, DIMENSIONI E PRESTAZIONI OFFERTE SIA CON L¿ESTETICA E LE FUNZIONALITà DEL MOBILE/COMPLEMENTO DI ARREDO SIA CON LE RICHIESTE DEL CLIENTE. LA CONFIGURABILITà DELLA LINEA COMPORTA LA PERSONALIZZAZIONE DEI PRODOTTI IN TERMINI DI DECORAZIONI PRESENTI, COLORAZIONI, TIPO DI ILLUMINAZIONE (O IN ALCUNI CASI ASSENZA) E DIMENSIONI. DA UN PUNTO DI VISTA DEL CICLO DI VITA DELLA NUOVA LINEA, I | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
219089 | The polya machinery: elucidating the molecular mechanisms of mrna polyadenylation, deadenylation and rna recognition | Gene expression is tightly regulated to allow rapid responses to cellular stimuli. In eukaryotes, the 3´ polyA tail of mRNAs plays key roles in post-transcriptional control. The Cleavage and Polyadenylation Factor (CPF), Ccr4–Not and Pan2–Pan3 multiprotein complexes add or remove polyA tails to regulate mRNA stability and efficiency of translation. They control expression of genes in the inflammatory response, miRNA-targeted gene silencing and expression of maternal mRNAs in oocyte development. These processes are deregulated in disease, including cancer and neurological disorders.
Although the proteins that add and remove polyA tails are known, their mechanisms are poorly understood. My lab recently established methods to reconstitute the polyA machinery. This led to new insights into the link between transcription and polyadenylation, new understanding of the molecular mechanisms of deadenylation, and details of RNA recruitment.
In this proposal, my objective is to understand the molecular basis for polyadenylation and deadenylation of specific mRNAs. This is now possible because of our novel methodological and biological advances. We will determine high-resolution structures of the polyA machinery using electron cryo-microscopy (cryo-EM), reconstitute their biochemical activities in vitro and study their in vivo functional roles. We use this integrated approach to study intact multiprotein complexes, not individual subunits or domains. This involves considerable technical challenges and an investment in developing high quality purifications and new structural methods. I will determine how the four enzymatic activities of CPF are coupled, the mechanisms by which Ccr4–Not targets specific RNAs, and the molecular basis for RNA recognition by Pan2–Pan3. Together, this will provide new biological and technological insights, leading to understanding of fundamental processes in gene expression and the role of polyA tails in disease. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
]
|
10.1051/0004-6361/201833576 | Planetary Tidal Interactions And The Rotational Evolution Of Low Mass Stars The Pleiades Anomaly | Context. The surface angular velocity evolution of low-mass stars is now globally understood and the main physical mechanisms involved in it are observationally quite constrained. However, while the general behaviour of these mechanisms is grasped, their theoretical description is still under ongoing work. This is the case, for instance, about the description of the physical process that extracts angular momentum from the radiative core, which could be described by several theoretical candidates. Additionally, recent observations showed anomalies in the rotation period distribution of open cluster, main sequence, early K-type stars that cannot be reproduced by current angular momentum evolution models. Aims. In this work, we study the parameter space of star-planet system’s configurations to investigate if including the tidal star-planet interaction in angular momentum evolution models could reproduce the anomalies of this rotation period distribution. Methods. To study this effect, we use a parametric angular momentum evolution model that allows for core-envelope decoupling and angular momentum extraction by magnetized stellar wind that we coupled to an orbital evolution code where we take into account the torque due to the tides raised on the star by the planet. We explore different stellar and planetary configurations (stellar mass from 0. 5 to 1. 0 M⊙ and planetary mass from 10 M⊕ to 13 Mjup) to study their effect on the planetary orbital and stellar rotational evolution. Results. The stellar angular momentum is the most impacted by the star-planet interaction when the planet is engulfed during the early main sequence phase. Thus, if a close-in Jupiter-mass planet is initially located at around 50% of the stellar corotation radius, a kink in the rotational period distribution opens around late and early K-type stars during the early main sequence phase. Conclusions. Tidal star-planet interactions can create a kink in the rotation period distribution of low-mass stars, which could possibly account for unexpected scatter seen in the rotational period distribution of young stellar clusters. | [
"Universe Sciences"
]
|
10.1016/j.fuel.2020.117186 | Nanoparticle modified polyacrylamide for enhanced oil recovery at harsh conditions | Silicon dioxide (SiO2) nanoparticles (NPs) have been recently proposed to increase the performance of polyacrylamide (PAM) for enhanced oil recovery (EOR) applications. However, SiO2/PAM nanocomposites tend to agglomerate or even desposit under harsh conditions such as high temperature-high salinity (HT-HS), which greatly decreases the potential for future field applications. In this work, SiO2 NPs were modified by (3-aminopropyl) triethoxysilane (M_SiO2) to create positively charged active groups that enabled strong interaction with PAM functional groups, leading to high dispersion stability. Three samples including M_SiO2/PAM, SiO2/PAM and NP-free PAM were synthesised in-situ via free radical polymerisation, and their thermal stability, rheological properties and the effect of aging time were studied. It was found that M_SiO2 could reduce the thermal degradation of the polymer and safeguard its backbone, resulting in much better thermal stability of PAM in harsh environments. After 90 days of aging, SiO2/PAM and NP-free PAM had 45 and 78% viscosity reduction; whereas only 10% reduction was observed for M_SiO2/PAM. In addition, core-flooding experiments showed that M_SiO2/PAM solutions produced more oil recovery than those from SiO2/PAM and NP-free PAM solutions at HT-HS condition. | [
"Materials Engineering",
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
]
|
W1983597949 | Scanning Structure–Activity Relationships with Structure–Activity Similarity and Related Maps: From <i>Consensus Activity Cliffs</i> to <i>Selectivity Switches</i> | Systematic description of structure-activity relationships (SARs) of data sets and structure-property relationships (SPRs) is of paramount importance in medicinal chemistry and other research fields. To this end, structure-activity similarity (SAS) maps are one of the first tools proposed to describe SARs using the concept of activity landscape modeling. One of the major goals of the SAS maps is to identify activity cliffs defined as chemical compounds with high similar structure but unexpectedly very different biological activity. Since the first publication of the SAS maps more than ten years ago, these tools have evolved and adapted over the years to analyze various types of compound collections, including structural diverse and combinatorial sets with activity for one or multiple biological end points. The development of SAS maps has led to general concepts that are applicable to other activity landscape methods such as "consensus activity cliffs" (activity cliffs common to a series of representations or descriptors) and "selectivity switches" (structural changes that completely invert the selectivity pattern of similar compounds against two biological end points). Herein, we review the development, practical applications, limitations, and perspectives of the SAS and related maps which are intuitive and powerful informatics tools to computationally analyze SPRs. | [
"Physical and Analytical Chemical Sciences",
"Computer Science and Informatics"
]
|
218339 | High-Pressure hydrogen booster for distributed small-medium refuelling stations | The market of hydrogen refuelling stations is expected to thrive, with more than 400 stations by 2023 only in Germany. Hydrogen mobility is today the only reliable alternative to electric vehicles since it does not suffer the limits in autonomy and charging time affecting electric vehicles, opening promising perspective to decarbonise the transport mass-market.
A widespread geographic coverage of the refuelling infrastructure is an unavoidable step to boost the hydrogen mobility, but the main bottleneck in the realization of this target is currently the high cost of refuelling stations. New cost-effective technologies for development of small-medium refuelling stations are eagerly demanded to give the initiative the proper initial sustainability.
HYDRUS aims towards this direction, providing a breakthrough high-performance compressor and a flexible and modular architecture for the refuelling station enabling
- to limit the initial costs of investments;
- to scale the size of the infrastructure by later addition of new modules;
- to increase the resilience, reliability and security of the refuelling infrastructure, by significantly reducing the size (or potentially avoid) of the high-pressure storage.
The core of HYDRUS proposal is a ""Hydraulic driven intensifier"" booster, allowing
- Compression capacity above 90 MPa to cope with the new fuelling protocols set by the SAE J2609 guideline;
- High flow rate (200-600 Nm3/h) during refilling of vehicles to fulfil the customers’ expectations of fuelling time in 3-5 minutes.
Our vision is to introduce a disruptive refuelling technology to make infrastructures more sustainable, safe and adaptable to evolving needs of H2 mobility.
The feasibility study aims to assess the opportunities and risk, as well as to plan the activities necessary
- To industrialize Hydrus booster
- To validate the HYDRUS architecture refuelling infrastructure
- To test the potential target market to achieve a successful business exploitation | [
"Products and Processes Engineering",
"Materials Engineering",
"Systems and Communication Engineering"
]
|
10.1126/science.aaw4295 | Protein crystallization promotes type 2 immunity and is reversible by antibody treatment | Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
617840 | Investigating the causes and consequences of replication stress in mammalian health | DNA damage (DD) is the cause of several diseases, including cancer, and it is also linked to the organ decline that arises in ageing. Yet, the contribution of different sources of DD to these processes is not understood. Sources of DD such as chromosome breaks, eroded telomeres or oxidative stress are been heavily investigated. For establishing my group, I decided to focus on a source of DD that arises every time a cell replicates its DNA, and which is known as replication stress (RS). In short, RS stands for the excessive accumulation of single-stranded DNA at replication forks that, due to its recombinogenic nature, can initiate genomic rearrangements. Consistently, RS is now known to be a key source of genomic instability in human tumors. In mammalian cells, a signalling cascade initiated by ATR and Chk1 kinases suppresses RS. Unfortunately, the essential nature of these kinases significantly limited the study of the RS-response in mammals. In the initial years of our lab we have developed several tools that facilitate the study of RS in mammals. These include a cellular system where ATR can be activated at will, potent and selective ATR inhibitors, and mice with reduced or increased levels of ATR and Chk1 kinases. These tools have allowed us to start exploring how RS impacts on cancer and ageing, as well as to investigate the potential of targeting ATR for cancer therapy. Yet, the field of RS is still poorly developed, and many basic questions are still in the need of answers.
This application outlines a plan for our research in the next five years, and explains how I propose to investigate RS at molecular, cellular and animal levels. Whereas I plan to capitalize on the tools (published and unpublished) that we have generated within the last few years, I also propose several innovative strategies for the study of the RS-response in mammals. This grant would allow us to consolidate our still young group as a solid laboratory for the study of RS in mammals. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
]
|
311542 | Deciphering cytosolic antibacterial immunity: from triggering bacteriolysis to Aim2 inflammasome activation | Bacteria replicating within host cells either multiply in membrane-bound compartment or escape into the host cytosol. The host cytosol has long been considered as a safe haven for bacteria. However, the host cytosol is armed with an array of innate immune receptors detecting cytosolic invasion. Furthermore, the macrophage cytosol displays a bacteriolytic activity, which is inducible by IFN. Surprisingly, the molecular mechanisms of this innate immune effector response are still largely uncharacterized. A ubiquitously expressed antimicrobial peptide, ubiquicidin has been described in the macrophage cytosol. Its relevance, its connection with macrophage-specific bacteriolytic activity and with IFN, remain to be deciphered. While cytosol-adapted bacteria are largely resistant to the bactericidal activity of the macrophage, lysis of a single bacterium triggers activation of the Aim2 inflammasome. Cytosolic bacteriolysis is thus key to orchestrate inflammasome-mediated innate immune responses. We propose here to characterize the bacteriolytic effector mechanisms, the regulation of this response and of the Aim2 inflammasome by IFN in infected macrophages. We will use two complementary bacterial models: F. tularensis, a cytosol-adapted bacterium and S. typhimurium sifA mutant, a bacterium lysed in the macrophage cytosol. We will develop three synergistic approaches:
i) the generation of novel tools to monitor cytosolic bacteriolysis
ii) hypothesis-driven investigations on the antimicrobial activity of the macrophage cytosol focusing on ubiquicidin to uncover the mechanisms of processing and targeting of this antimicrobial peptide
iii) screening of IFN-inducible genes to identify novel players involved in the cytosolic bacteriolytic activity and in inflammasome regulation.
We believe this project should reveal the innate immune effector mechanisms of the macrophage cytosol i.e. how the macrophage kills cytosolic bacteria and orchestrates further immune responses. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
interreg_1851 | Miniaturization technology: synergies of research and innovation to enhance the economic development of the Adriatic | Public and Private entities in Adriatic and elsewhere have identified a challenge on finding a common language and field of interest between research & innovation and reaching a common understanding of the commercial imperatives in terms of economic and social development. IPATECH aims at developing a network for integrated trans-regional cooperation between knowledge & technology providers, innovation intermediaries and SMEs in the agro-food sector and thus facilitate industrial and commercial exploitation of research results by taking into account technology and other “soft” aspects in the process. Innovative food production systems, higher quality standards, and an evolution towards value-added products are important ingredients in meeting the challenges posed by more competitive food markets. Small and medium-sized enterprises (SMEs) are vulnerable in this changing environment. SME managers have a limited amount of time available to learn about market trends and policies which could affect their business. The potential of modern agro-food business to promote economic growth in the countryside is huge. We believe that the potential of modern agribusiness is, however, underutilized. Indeed, in many countries in Adriatic, small-scale producers and small- and medium-scale enterprises are relegated to lower-value markets. In this respect, IPATECH’s impetus is to boost the innovation process in the sector and thus the region. More specifically, the project aims at Establishment of an Agro-Food Transnational cooperation network between public and private entities stimulating the exchange of information and experiences on research and innovation in the sector. In parallel, the project will boost Support research-driven innovations in the participating regions as well as provision of a portfolio of tools, technologies and systems to foster research & innovation in Agro-food Sector and share Best Practices. Furthermore, IPATECH will facilitate capacity Building and transfer of know-how with emphasis to the “soft” side of innovation and the role of “human capital” on stimulating technology and know-how transfer for efficient transfer of currently matured technologies to rural SMEs, associations, clusters technology poles involved in the Agro-food Sector. The core of concrete activities will be deployed by Transfer of technological innovations: to assist agro-food SMEs of the participating Regions in becoming more competitive and adopt in new technologies and solutions developed through research (eg. Miniaturized Production lines and the improvement of the quality of the agro-food products) as well as Establishment of Agro-food Innovation Centres and Agro-food Technology & Innovation Platform to assist identification of research commercialization opportunities. Finally, emphasis is given to main-streaming of results and lessons learned at market and policy level; to promote synergies between regional and research policies in each participating Region, highlight additional sectors of intervention, future initiatives, funding and governance models guaranteeing the future sustainability and valorization of the project results and Network Operation after the end of the project’s lifespan. The partnership includes leading private and public establishments, a Research Institute with experience in Agro-food, Innovation Intermediaries organization engaged in rural development that usually cooperate with agro-food SMEs from nine ADRIATIC territories (from Croatia, Bosnia and Herzegovina, Albania, Italy & Greece). The innovating character of the project refers to its capacity of overcoming agro-food SMEs isolation in terms of having access and participating to technology innovation and its transferability at a national and transnational level. SMEs will no longer be only exclusive beneficiaries of innovation, but through IPATECH conditions will be set to allow them to be one of the most important participant of this process. | [
"Products and Processes Engineering",
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems"
]
|
10.1038/s41598-018-36201-w | A critical review of anthropological studies on skeletons from European plague pits of different epochs | In historical times, plague epidemics intermittently ravaged Europe for more than 1,400 years, and still represent a threat in many countries all over the world. A debate is ongoing about the past plague, if it killed randomly in a population or discriminated among persons on the basis of their biological features. To address questions of plague lethality, we reviewed a large number of anthropological studies published in the last twenty years on victims of the past pestilences in Europe. In particular, we focused on data concerning demography (age at death and sex determination), and health status (skeletal biomarkers). We applied to these data a model system based on Multiple Linear Regression, which aimed to discern among possible predictors of sex-selective plague lethality in entire populations, in different periods and regions. Based on available data, we lack evidence for general trends of association between biological features. Differences in sex ratio are more likely due to the original population compositions or to distinct cultural behaviours of the two genders. We concluded that generalizations on biological evidence are not feasible for ancient plagues if we exclude that the infection possibly killed primarily persons between 5–10 and 20–35 years of age. | [
"The Study of the Human Past",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution"
]
|
W1754464718 | Biological Responses of Agricultural Soils to Fly-Ash Amendment | The volume of solid waste produced in the world is increasing annually, and disposing of such wastes is a growing problem. Fly ash (FA) is a form of solid waste that is derived from the combustion of coal. Research has shown that fly ash may be disposed of by using it to amend agricultural soils. This review addresses the feasibility of amending agricultural field soils with fly ash for the purpose of improvings oil health and enhancing the production of agricultural crops. The current annual production of major coal combustion residues (CCRs) is estimated to be -600 million worldwide, of which about 500 million t (70-80%) is FA (Ahmaruzzaman 2010). More than 112 million t of FA is generated annually in India alone, and projections show that the production (including both FA and bottom ash) may exceed 170 million t per annum by 2015 (Pandey et al. 2009; Pandey and Singh 20 I 0). Managing this industrial by-product is a big challenge, because more is produced each year, and disposal poses a growing environmental problem.Studies on FA clearly shows that its application as an amendment to agricultural soils can significantly improve soil quality, and produce higher soil fertility. What FA application method is best and what level of application is appropriate for any one soil depends on the following factors: type of soil treated, crop grown, the prevailing agro climatic condition and the character of the FA used. Although utilizing FA in agricultural soils may help address solid waste disposal problems and may enhance agricultural production, its use has potential adverse effects also. In particular, using it in agriculture may enhance amounts of radionuclides and heavy metals that reach soils, and may therefore increase organism exposures in some instances. | [
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
]
|
W1884262368 | PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes | Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance.In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes.Two hundred and thirty-four patients with type 2 diabetes were included in this study.LFC was evaluated using (1) H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest(®).Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (≥60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis.This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1002/ps.5677 | Target the core: durable plant resistance against filamentous plant pathogens through effector recognition | Plant pathogens colonize their host through the secretion of effector proteins that modulate plant metabolism and immune responses to their benefit. Plants evolve towards effector recognition, leading to host immunity. Typically, pathogen effectors are targets for recognition through plant receptors that are encoded by resistance genes. Resistance gene mediated crop immunity puts a tremendous pressure on pathogens to adapt and alter their effector repertoire to overcome recognition. We argue that the type of effector that is recognized by the host may have considerable implications on the durability of resistance against filamentous plant pathogens. Effector genes that are conserved among pathogens and reside in core genome regions are most likely to hold indispensable virulence functions. Consequently, the cost for the pathogen to overcome recognition by the host is higher than for diversified, host-specific effectors with a quantitative impact on virulence. Consequently, resistance genes that directly target conserved effector proteins without the interception of other effector proteins are potentially excellent resistance resources. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
]
|
10.3389/fimmu.2017.00390 | Disarming cellular alarm systems-manipulation of stress-induced NKG2D ligands by human herpesviruses | The coevolution of viruses and their hosts led to the repeated emergence of cellular alert signals and viral strategies to counteract them. The herpesvirus family of viruses displays the most sophisticated repertoire of immune escape mechanisms enabling infected cells to evade immune recognition and thereby maintain infection. The herpesvirus family consists of nine viruses that are capable of infecting humans: herpes simplex virus 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), roseoloviruses (HHV-6A, HHV-6B, and HHV-7), and Kaposi's-sarcoma-associated herpesvirus (KSHV). Most of these viruses are highly prevalent and infect a vast majority of the human population worldwide. Notably, research over the past 15 years has revealed that cellular ligands for the activating receptor natural-killer group 2, member D (NKG2D)-which is primarily expressed on natural killer (NK) cells-are common targets suppressed during viral infection, i. e. , their surface expression is reduced in virtually all lytic herpesvirus infections by diverse mechanisms. Here, we review the viral mechanisms by which all herpesviruses known to date to downmodulate the expression of the NKG2D ligands. Also, in light of recent findings, we speculate about the importance of the emergence of eight different NKG2D ligands in humans and further allelic diversification during host and virus coevolution. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1007/JHEP03(2016)014 | Towards The Amplituhedron Volume | It has been recently conjectured that scattering amplitudes in planar N=4 super Yang-Mills are given by the volume of the (dual) amplituhedron. In this paper we show some interesting connections between the tree-level amplituhedron and a special class of differential equations. In particular we demonstrate how the amplituhedron volume for NMHV amplitudes is determined by these differential equations. The new formulation allows for a straightforward geometric description, without any reference to triangulations. Finally we discuss possible implications for volumes related to generic N^kMHV amplitudes. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
W2340652522 | Mega-project meltdown: Post-politics, neoliberal urban regeneration and Valencia’s fiscal crisis | Drawing on the literature of post-politics and post-democracy, the literature of neoliberalism as mode of governance and the study of the city of Valencia’s long-standing emphasis on the development of prestige mega-projects of iconic architecture as a means to achieve economic regeneration and urban revitalisation, this paper evaluates the social and economic effects of urban mega-projects and analyses them as conduits of neoliberal globalisation and de-politicisation of the public sphere. On the one hand, an urban policy based on the use of mega-projects represents a turn from welfarism to entrepreneurialism which, beyond the evident urban transformation and re-imaging, results in an increase in social inequality, the creation of precarious jobs, and an underinvestment in social services. On the other hand, the mechanisms used to implement mega-projects – including both exceptionality measures and privatisation of management through the creation of semi-public delivery bodies – result in a lack of transparency and democratic control, which in turn lead to more authoritative and privatised forms of decision-making. Moreover, mega-projects – through their focus on expertise and technocracy and a populist politics and discourse constructed around them – play a crucial role in the erosion of democracy and the establishment of a consensual politics where ideological struggle does not exist. | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions",
"Human Mobility, Environment, and Space"
]
|
10.1016/j.molcel.2012.05.048 | MCM8- and MCM9-Deficient Mice Reveal Gametogenesis Defects and Genome Instability Due to Impaired Homologous Recombination | We generated knockout mice for MCM8 and MCM9 and show that deficiency for these genes impairs homologous recombination (HR)-mediated DNA repair during gametogenesis and somatic cells cycles. MCM8-/- mice are sterile because spermatocytes are blocked in meiotic prophase I, and females have only arrested primary follicles and frequently develop ovarian tumors. MCM9-/- females also are sterile as ovaries are completely devoid of oocytes. In contrast, MCM9-/- testes produce spermatozoa, albeit in much reduced quantity. Mcm8-/- and Mcm9-/- embryonic fibroblasts show growth defects and chromosomal damage and cannot overcome a transient inhibition of replication fork progression. In these cells, chromatin recruitment of HR factors like Rad51 and RPA is impaired and HR strongly reduced. We further demonstrate that MCM8 and MCM9 form a complex and that they coregulate their stability. Our work uncovers essential functions of MCM8 and MCM9 in HR-mediated DSB repair during gametogenesis, replication fork maintenance, and DNA repair. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
249397 | The eating body in Western practice and theory | Human bodies eat. But what does this entail? The proposed project will explore how the eating body is shaped in different Western practices. These will include nutritional research and health care clinics, sites that have a far-reaching impact on how we eat. Four related sub-projects will trace the most relevant contrasts: (1) the eating body's health: limiting calorie intake versus maximising satisfaction; (2) the eating body's sensitivity: on tasting in various practices; (3) the eating body and other eaters: on different ways of relating individual and collective; (4) the eating body and its environment: on absorbing food, excreting waste and different bodily boundaries. These four sub-projects will together inform an anthropology of the eating body in Western practices. A fifth sub-project will attend to the eater in theory . Eating may be ubiquitous in practice, but it is strikingly absent from theorising in the Western philosophical tradition. This has profound implications for social science repertoires, which tend to include an actor modelled on the neuromuscular body. This actor sees, hears, moves and manipulates, but does not eat. Drawing on what we learn about the eating body in the empirical parts of the study, the fifth sub-project will model the actor on the eater. Eaters do not observe from a distance, but are mixed up with their surroundings. They do not judge impartially, but appreciate their food as they destroy it. Their metabolic activity, distributed over every cell, does not depend on central control. The theoretical possibilities that follow, will be experimentally explored. Thus the project aims to substantially enrich the Western tradition by feeding it with lessons drawn from its own marginalised experiences. | [
"Studies of Cultures and Arts",
"Texts and Concepts",
"The Human Mind and Its Complexity"
]
|
W973836814 | Air Pollution and Serum Glucose Levels | Recent studies demonstrated an adverse effect of chronic exposure to air pollution (AP) on metabolic syndrome and its components. In a population-based study, we investigated the association between exposure to ambient AP and serum glucose (SG), among subjects with normal glucose, impaired fasting glucose (IFG), and diabetes mellitus (DM).
We included 1,063,887 SG tests performed in 131,882 subjects (years 2001–2012). Exposure data included daily levels of SO2, NO2 and other pollutants of industrial, traffic, and nonanthropogenic sources. Demographical, clinical, and medications purchase data were assessed. Log-transformed SG levels were analyzed by linear mixed models adjusted for seasonal variables and personal characteristics.
SG increases (%increase [95% CI]), among subjects with normal glucose, IFG, and DM, respectively, were associated with 6.36 ppb increase of NO2 measured 24 to 72 hours before the test (0.40% [0.31%; 0.50%], 0.56% [0.40%; 0.71%], and 1.08% [0.86%; 1.29%]); and with 1.17 ppb increase of SO2 measured 24 hours before the test (0.29% [0.22%; 0.36%], 0.20% [0.10%; 0.31%], and 0.33% [0.14%; 0.52%]). Among DM population, weakest association was observed among patients treated with Metformin (0.56% increase in SG [0.18%; 0.95%]).
In conclusion, NO2 and SO2 exposure is associated with small but significantly increased levels of SG. Although DM patients were found to be more susceptible to the AP induced SG variations, Metformin treatment seem to have a protective effect. Given the chronic lifetime exposure to AP and the broad coverage of the population, even small associations such as those found in our study can be associated with detrimental health effects and may have profound public health implications. | [
"Earth System Science",
"Physiology in Health, Disease and Ageing"
]
|
310890 | NLRs AS TRANSCRIPTIONAL REGULATORS | MHC molecules are central to our immune system and are therefore also involved in several pathologies. MHCII transcription is controlled by proximal promoter sequences, which are cooperatively bound by several factors forming the ‘MHC enhanceosome’. Upon recruitment to this complex, the NLR family member CIITA promotes MHCII transcription.
We recently found that our mice deficient for the NLR NLRC5 exhibit markedly reduced MHCI expression in lymphocytes. Importantly, endogenous NLRC5 occupies H-2 proximal promoter regions and drives gene transcription.
We now plan to characterize novel NLR-mediated transcriptional regulatory pathways controlling MHC expression. We will investigate the enhanceosome and the transcriptional regulators interacting with NLRC5 as well as the role of NLRC5 in gene expression more broadly. We will also address the function of other NLRs that are potentially controlling gene transcription, paying particular attention at their potential role in the regulation of classical and non-classical MHC genes. Finally, we will try to detail the underlying molecular mechanisms.
Novel aspects of MHC transcriptional regulation are emerging, highlighting a combinatorial system wherein NLRs play a more general role than realized so far. A better understanding of the mechanisms regulating MHC transcription is fundamental to design novel therapeutic approaches relevant to immune disorders, malignancies, and infertility. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
631104 | Catalytic reforming of glycerol to hydrogen and biopropane in hydrothermal media | The ultimate goal of this 15 months Fellowship, entitled “Catalytic Reforming of Glycerol to Hydrogen and Biopropane in Hydrothermal Media” (HYDROGAS) is to train a talented researcher through a research project focused on the development of novel process to make viable the use of the glycerol co-product derived during the use of vegetable oils for the production of liquid hydrocarbon biofuels.. This innovative HYDROGAS project aims to investigate for the first time the potential of a novel two-stage catalytic process to produce hydrogen and biopropane from catalytic reforming of glycerol in hydrothermal media. The two-stage approach would enable deriving all the hydrogen requirements for the HEFA by using glycerol as a hydrogen-source. This can contribute to a positive process economics for the HEFA bio-jet fuel production. The transfer of knowledge between the researcher, the host, the supervisor, the students and international research groups will be very important for the dissemination of the learning through training, publications in journals of high impact factor, development of patent and participation in international conferences. The Fellow will receive access to an innovative project experience at the host: Sustainable Chemicals Laboratory in the European Bioenergy Research Institute, Aston University, UK (Dr. Jude Onwudili), and at academic secondment partner: University of Zaragoza, Spain (Prof Lucia Garcia). HYDROGAS aims to investigate the development of a new methodology to produce biopropane for a large-scale deployment in substitution for petroleum-based LPG that can contribute to lowering carbon emissions. In addition, the thermodynamic study to consolidate the catalytic reforming from crude glycerol will be a positive challenge for this team to work together and evaluate the expected results. The HYDROGAS will permeate the whole fellowship and will be a valuable and challenging mixture of scientific research and training for the Fellow. | [
"Products and Processes Engineering",
"Physical and Analytical Chemical Sciences"
]
|
221838 | A smart, energy autonomous, universal and cost-effective dynamic passenger information system | PIXEL is a Polish B2B SME, a pioneer and market leader in the development and delivery of passenger information system
in the Transport Sector. We operate in an industry that is expected to growth to $20.34 Billion by 2019 at a CAGR of 26.5%.
We develop all our innovative products with the belief and values of freedom of mobility. Due to language barriers and the
fact that only 19% of Europeans are bilingual the Public Transport needs to be innovative and leverage advances in Smart
City and Intelligent Transport System technologies to attract more citizens and foreigners to use the Public Transport and
facilitate freedom of mobility. To solve this problem we have created E-APIS, a smart, energy-autonomous, universal and
cost-effective dynamic passenger information system that removes all communication barriers and radically improves
freedom-of-movement in public transport across the EU Member States. The innovation lies in the integration of advanced
displays and mobile communications that are able to provide real-time information in any chosen language and low-power
technologies that allow 24/7 365 days of autonomous power through renewable energy sources.
Our solution provides a high economic impact to Transport Operators since it removes energy bills and installation costs and
gives them a new revenue stream. These qualities will shorten payback periods and make the investment sustainable and
profitable. We foresee that E-APIS will add over €10 Million to our annual revenue by 2023, increase our annual profits by
25% and grow direct employment by 30% by 2021 (5 year ROI 14). Phase 1 of this innovative project is to carry out an
elaborate Feasibility Study and Business Plan to get E-APIS from TRL6 to TRL9 and commercialise it. | [
"Products and Processes Engineering",
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
320789 | A laser-cooled molecular fountain to measure the electron EDM | I propose to build an instrument that cools YbF molecules to microK temperature using laser light, and throws them up as a fountain in free fall. This will be used to detect CP-violating elementary particle interactions that caused our universe to evolve an excess of matter over antimatter These interactions cause the charge distribution of the electron to be slightly non-spherical and it is this property, the permanent electric dipole moment (EDM), that the ultracold molecules will sense.
Laser cooling of any molecule is very new, with first results emerging from a few laboratories including mine. Developing a fountain of molecules will be a major advance in the state of the art. As well as being the key to the new EDM instrument, this will be important in its own right because ultracold molecules have major applications in chemistry, quantum information processing and metrology.
In the fountain, the electron spin of each molecule will be polarized. On applying a perpendicular electric field, the spins will precess in proportion to the EDM. At present the (warm) YbF molecules in my lab precess for only 1ms. This gives us world-leading sensitivity, but has not been sufficient to detect the CP-violating forces being sought. The fountain however will achieve precession times of almost a second, giving over 1000x more rotation. The increase in sensitivity should reveal a clear EDM, providing information about the fundamental laws of physics, and the important CP-violating physics of the early universe, which is currently not understood.
By advancing the preparation of ultracold molecules, this project will address a key question in particle physics and cosmology: the nature of CP-violating physics beyond the standard model. The approach is radically different from standard accelerator physics and complements it. The sensitivity is sufficient to detect some proposed new forces that are beyond the reach of any current collider experiment. | [
"Fundamental Constituents of Matter",
"Physical and Analytical Chemical Sciences"
]
|
173887 | Deploying high capacity dense small cell heterogeneous networks | Broadband mobile networks are experiencing exponential traffic growth. It is predicted that this trend will continue in the next five to ten years with an estimated compound annual growth rate of 0.6 to 1.0. Hence the traffic (mostly data) carried by a mobile operator’s network in 2022 could be over 1000 times of that in 2012. This traffic growth presents a huge challenge to both the mobile industry and to academic researchers.
Along with increased spectrum efficiency, spectrum bandwidth expansion and traffic offloading through WiFi, small cell deployment is regarded as one of the most promising ways to meet the use of broadband mobile service in both outdoor and in particular indoor scenarios in the next decade. The deployment of small cells in a macrocell coverage area leads to a multi-tier heterogeneous network (HetNet), in which a mix of access node types, such as macrocell, femtocell and relay, will co-exist. Despite the current research and development on small cell/HetNet from both industry and academia, there are still many challenges to be addressed and questions to be answered for successful small cell and HetNet deployment. These challenges range from the lack of fundamental understanding of HetNet network capacity to the need of Radio Access Network (RAN) Planning and Optimisation (PO) tool for HetNet deployment involving both indoor and outdoor scenarios.
The DECADE project adopts the scheme of Research and Innovation Staff Exchange (RISE), with the effect of inter-sectorial efforts and knowledge integration to tackle the challenges in HetNet planning and optimization. The research consists in fundamental capacity analysis, system modeling, algorithm development, and performance engineering for HetNets. In addition, DECADE serves as a solid platform to promote long-term collaboration between academia and industry collaboration in a rapidly evolving area of Information and Communication Technologies (ICT) in Europe. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
984162 | Dna nanohydrogel loaded liposomal formulations for high loading efficiency of antimicrobial drugs against intracellular bacterial and topical biofilm infections | Dr. Sybil Obuobi was awarded her PhD in Pharmacy at the National University of Singapore (Singapore) in July 2018 and is very excited to pursue a postdoctoral fellowship at the University of Tromso The Arctic University of Norway (UiT, Norway) under the supervision of Prof. Natasa Skalko-Basnet, a renowned expert in advanced drug delivery. Their project will exploit DNA nanohydrogels, as a novel universal platform to improve the loading efficiency of antimicrobials in mannosylated liposomes against intracellular and topical biofilm infections. This approach fills the current research gap for high drug loading innovative systems in nanomedicine and holds great promise to improve drug efficacy against difficult-to-reach pathogens thus, there is immense potential for new patentable technologies/products. This area of research will advance knowledge in antimicrobial drug delivery and the outcomes will appeal to formulation scientists, R&D scientists and people with persistent skin infections that impose significant economic challenge and contribute to the spread of antimicrobial resistance. With access to state-of-the-art equipment and interdisciplinary environment within the participating organisations (UiT, University of Helsinki and BIOTEC Pharmacon ASA) and administrative support, Dr. Obuobi will acquire new skills in life sciences, expertise in state-of the art biofilm models, hands-on teaching experience, transferrable skills in grant/patent applications and project management alongside new knowledge in product development. Against the backdrop of her notable achievements as a young scientist, she has the capacity to attain research growth through this fellowship and will seize this opportunity to diversify her competency, improve her record of publications, gain independence, build new international networks and apply for an ERC-StG grant- outputs that are expected benchmarks for academic appointments and essential to launch her career within Norway/Scandinavia. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering"
]
|
W2220710686 | Should walking aids be used in the assessment of walking in persons with stroke? | Results: The results of the multiple regression analysis revealed that the number of single heel-raise repetitions and the passive range of motion for the ankle joint (dorsi-flexion with the knee flexed) were significantly correlated with the one-step value. Conclusion(s): Our data indicated that both an increased number of single heel-raise repetitions and passive range of motion for the ankle joint (dorsi-flexion with the knee flexed) were associatedwith a greater one-step value. In other words, the acquisition of plantar-flexion strength and greater dorsi-flexion angle more rapidly led to the patient’s ability to resume a normal gait after Achilles tendon repair. The onestep test is affected by the strength and mobility of the ankle and is useful as an ankle joint function evaluation tool. Implications: The one-step test is an evaluation tool for ankle joint function that is easily measurable anywhere. This new test for patients after Achilles tendon repair is clinically significant. | [
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1017/S0022377813000354 | Relativistic Collisionless Shocks Formation In Pair Plasmas | Collisionless shocks are ubiquitous in astrophysics and in the laboratory. Recent numerical simulations and experiments have shown how these can arise from the encounter of two collisionless plasma shells. When the shells interpenetrate, the overlapping region turns unstable, triggering the shock formation. As a first step toward a microscopic understanding of the process, we here analyze in detail the initial instability phase. On the one hand, 2D relativistic PIC simulations are performed where two unmagnetized, symmetric, and initially cold pair plasmas collide. On the other hand, the instabilities at work are analyzed, as well as the field at saturation and the seed field which gets amplified. For mildly relativistic motions and onward, Weibel modes with ω=0+iδ govern the linear phase. We derive an expression for the duration of the linear phase in reasonable agreement with the simulations. | [
"Fundamental Constituents of Matter",
"Universe Sciences"
]
|
10.1002/cphc.201800935 | Microsecond Protein Dynamics from Combined Bloch-McConnell and Near-Rotary-Resonance R <inf>1p</inf> Relaxation-Dispersion MAS NMR | Studying protein dynamics on microsecond-to-millisecond (μs-ms) time scales can provide important insight into protein function. In magic-angle-spinning (MAS) NMR, μs dynamics can be visualized by R 1ρ rotating-frame relaxation dispersion experiments in different regimes of radio-frequency field strengths: at low RF field strength, isotropic-chemical-shift fluctuation leads to “Bloch-McConnell-type” relaxation dispersion, while when the RF field approaches rotary resonance conditions bond angle fluctuations manifest as increased R 1ρ rate constants (“Near-Rotary-Resonance Relaxation Dispersion”, NERRD). Here we explore the joint analysis of both regimes to gain comprehensive insight into motion in terms of geometric amplitudes, chemical-shift changes, populations and exchange kinetics. We use a numerical simulation procedure to illustrate these effects and the potential of extracting exchange parameters, and apply the methodology to the study of a previously described conformational exchange process in microcrystalline ubiquitin. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2029605564 | Evaluation of Accuracy and Stability of the Classical SPH Method Under Uniaxial Compression | The accuracy and stability of the classical formulation of the smoothed particle hydrodynamics (SPH) method for modelling compression of elastic solids is studied to assess its suitability for predicting solid deformation. SPH has natural advantages for simulating problems involving compression of deformable solids arising from its ability to handle large deformation without re-meshing, complex free surface behaviour and tracking of multiple material interfaces. The ‘classical SPH method’, as originally proposed by Monaghan (in Ann Rev Astron 30:543–574, 1992, Rep Prog Phys 68:1703–1759, 2005), has become broadly established as a robust method in different areas, especially involving fluid flows. However, limited attention has been paid to understanding of its numerical performance for elastic deformation problems. To address this, we evaluate the classical SPH method to explore its stability, accuracy and convergence and the effect of numerical parameters on elastic solutions using a generic uniaxial stress test. Short term transient and long term uniform state SPH solutions agree well with those from the finite element method (FEM). The SPH elastic deformation solution showed good convergence with increasing particle resolution. The tensile instability stabilisation method was found to have little impact on the solution, except for higher values of the correction factor which then produce small amplitude benign artificial banded stress patterns. The use of artificial viscosity is able to eliminate the instability and improve the accuracy of the solutions. Overall, the classical SPH method appears to be robust and suitable for accurate modelling of elastic solids under compression. | [
"Condensed Matter Physics",
"Products and Processes Engineering"
]
|
10.1016/j.ymeth.2018.03.014 | 3D structure determination of amyloid fibrils using solid-state NMR spectroscopy | The amyloid fold is structurally characterized by a typical cross-β architecture, which is under debate to represent an energy-favourable folding state that many globular or natively unfolded proteins can adopt. Being initially solely associated with amyloid fibrils observed in the propagation of several neurodegenerative disorders, the discovery of non-pathological (or “functional”) amyloids in many native biological processes has recently further intensified the general interest invested in those cross-β supramolecular assemblies. The insoluble and non-crystalline nature of amyloid fibrils and their usually inhomogeneous appearance on the mesoscopic level pose a challenge to biophysical techniques aiming at an atomic-level structural characterization. Solid-state NMR spectroscopy (SSNMR) has granted breakthroughs in structural investigations on amyloid fibrils ranging from the assessment of the impact of polymorphism in disease development to the 3D atomic structure determination of amyloid fibrils. First landmark studies towards the characterization of atomic structures and interactions involving functional amyloids have provided new impulses in the understanding of the role of the amyloid fold in native biological functions. Over the last decade many strategies have been developed in protein isotope labelling, NMR resonance assignment, distance restraint determination and 3D structure calculation of amyloid fibrils based on SSNMR approaches. We will here discuss the emerging concepts and state-of-the-art methods related to the assessment of amyloid structures and interactions involving amyloid entities by SSNMR. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
639070 | Accommodating New Interests at Sea: Legal Tools for Sustainable Ocean Governance | This research project will develop a theoretical framework and legal tools to aid scholars and stakeholders (law and policy-makers, private investors, environmental NGOs) in managing competing interests in the offshore economic sector. The offshore sector is expanding and activities at sea are increasing (e.g., deep seabed mining, oil and gas extraction, renewable energy technologies, etc.). This situation threatens the health of the marine environment and its biodiversity. It also impacts traditional uses of the sea, such as navigation and fishing. New activities pose major challenges for the sustainable management of the oceans, and they highlight competing interests that the law needs to accommodate, such as:
- protecting the marine environment and conserving its biodiversity;
- mitigating climate change effects;
- guaranteeing the continuity of the relevant economic activities;
- guaranteeing energy efficiency and security; and
- protecting the rights of local communities and populations.
This project will answer the following research question: how can the law contribute to the sustainable use of the oceans and strike a balance between competing interests at sea? The law pertaining to ocean governance is fragmented into regimes that are imbued by different interests. The project will begin by analysing three legal frameworks, which are the most relevant for the offshore industry: the law of the sea, climate change law and energy law. It will focus on the operation of the offshore industry and on the competing interests, which have influenced the respective fields of law. This will allow identifying patterns of regime interaction and assessing their impact on the different uses of the sea. The research will ultimately offer a theory of interest- and regime-interaction in ocean governance and thus create a comprehensive framework for the development of legal tools(briefs, recommendation, which will contribute to sustainable ocean governance. | [
"Institutions, Governance and Legal Systems",
"Environmental Biology, Ecology and Evolution"
]
|
W2969760028 | Flexible CO2 laser fiber: first look at the learning curve required in gynecological laparoscopy training | The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible.Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant.Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser.Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Products and Processes Engineering"
]
|
10.1086/685083 | Constancy In Functional Space Across A Species Richness Anomaly | The relationship between large-scale gradients in species richness and functional diversity provides important information regarding the mechanisms driving patterns of biodiversity. A classic hypothesis in ecology is that strong interspecific interactions should result in an increase in the functional volume of assemblages as the species richness increases, whereas climatic constraints may result in no change in functional volume. Most research of this kind examines latitudinal gradients in species richness, but the results are likely confounded by underlying gradients in climate and phylogenetic composition. We take an alternative approach that examines functional richness across a tree species richness anomaly where species richness doubles from Europe to eastern North America. The results demonstrate that the functional richness on both continents saturates at a similar point as species richness increases and that the packing of functional space becomes tighter. Further, the species richness anomaly is driven primarily by genera unique to North America, but those genera contribute less than expected functional richness to the region, indicating a high level of redundancy with genera shared between the continents. Taken together, the results indicate that the species richness anomaly is associated with diversification within a climatically constrained trait space. More generally, the work demonstrates the power of utilizing species richness anomalies in biodiversity research, particularly when they are coupled with information regarding organismal function. | [
"Environmental Biology, Ecology and Evolution"
]
|
216089 | Communication systems for next-generation railways | MISTRAL will elaborate the Technical Specification of the future communication system for all railways in light of the migration from the current obsolete GSM-R.The new radio system will leverage the broadband capacity of IP-based wireless communication to enhance signaling but also to make possible innovative services for both users and train automation/control.To achieve the objective, MISTRAL will generate firstly a portfolio of foreseeable future communication scenarios. Then, a Techno-Economic Proposition consistent with future scenarios will be defined, including a portfolio of innovative services ushered-in by new technologies and compliant with new users requirements as well as with safety, security and QoS requirements. Such Techno-Economic proposition will be subject to a Business Viability Analysis - meant to gauge and optimize the total-cost-of-ownership of the new communication system - and to a Technical Viability Analysis that will investigate the compliance with the new requirements. Subsequently, the results of such Business and Technical Viability Analysis will be used as basis to refine and finalize the Validated Techno-Economic proposition, which will thus rely on an optimized life-cycle cost and on a sound portfolio of innovative services. The Validated Techno-Economic proposition will be the main output of MISTRAL, i.e. the 'Technical Specification' scope of the topic. Its design and validation will be supported by an External Stakeholder Committee, involving selected key players in the Railway domain, external to the MISTRAL Consortium. In addition, MISTRAL will disseminate project findings to relevant stakeholders and communities and will ensure the sustainability and impact of the new specified communication system, In terms of far-reaching impact, MISTRAL will lay the foundations for the next-generation train-to-wayside communication systems, paving the way for a more competitive, attractive and sustainable European railway ecosystem. | [
"Systems and Communication Engineering",
"Products and Processes Engineering"
]
|
10.1007/978-3-662-54365-8_7 | Removing Erasures With Explainable Hash Proof Systems | An important problem in secure multi-party computation is the design of protocols that can tolerate adversaries that are capable of corrupting parties dynamically and learning their internal states. In this paper, we make significant progress in this area in the context of password-authenticated key exchange (\(\textsf {PAKE}\)) and oblivious transfer (\(\textsf {OT}\)) protocols. More precisely, we first revisit the notion of projective hash proofs and introduce a new feature that allows us to explain any message sent by the simulator in case of corruption, hence the notion of Explainable Projective Hashing. Next, we demonstrate that this new tool generically leads to efficient \(\textsf {PAKE}\) and \(\textsf {OT}\) protocols that are secure against semi-adaptive adversaries without erasures in the Universal Composability (UC) framework. We then show how to make these protocols secure even against adaptive adversaries, using non-committing encryption, in a much more efficient way than generic conversions from semi-adaptive to adaptive security. Finally, we provide concrete instantiations of explainable projective hash functions that lead to the most efficient \(\textsf {PAKE}\) and \(\textsf {OT}\) protocols known so far, with UC-security against adaptive adversaries, without assuming reliable erasures, in the single global CRS setting. | [
"Computer Science and Informatics"
]
|
223143 | Influence-Based decision-making in uncertain environments | Decision-theoretic sequential decision making (SDM) is concerned with endowing an intelligent agent with the capability to choose actions that optimize task performance. SDM techniques have the potential to revolutionize many aspects of society and recent successes, e.g., agents that play Atari games and beat a world champion in the game of Go, have sparked renewed interest in this field.
However, despite these successes, fundamental problems of scalability prevents these methods from addressing other problems with hundreds or thousands of state variables. For instance, there is no principled way of computing an optimal or near-optimal traffic light control plan for an intersection that takes into account the current state of traffic in an entire city. I will develop one in this project.
To achieve this, I will develop a new class of influence-based SDM methods that overcome scalability issues for such problems by using novel ways of abstraction. Considered from a decentralized system perspective, the intersection’s local problem is manageable, but the influence that the rest of the network exerts on it is complex. The key idea is that by using (deep) machine learning methods, we can learn sufficiently accurate representations of such influence to facilitate near-optimal decisions.
This project will construct a theoretical framework for such approximate influence representations and SDM methods that use them. Scalability of these methods will be demonstrated by rigorous empirical evaluation on two simulated challenge domains: traffic lights control in an entire city, and robotic order picking in a large-scale autonomous warehouse.
If successful, INFLUENCE will produce a range of influence-based SDM algorithms that can, in a principled manner, deal with a broad range of very large complex problems consisting of hundreds or thousands of variables, thus making an important step towards realizing the promise of autonomous agent technology. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
172011 | Product-Service symbiotic systems | Product-service solutions are not a novelty for manufacturing domain, in particular for Europe. Services are becoming more and more not just an optional adjunct to products, but they are integral part of manufacturing industries’ offer, able to differentiate the product value proposition, to take a significant part of the revenue stream and even to substitute the traditional selling of products with more innovative service-oriented business models. There are still 5 main obstacles which are currently preventing service innovation to be pervasively adopted by all EU manufacturing industries, SMEs included:
I. Products and Services : How to preserve the specific characteristics of product and services in a value chain, without creating isolated and not interconnected walled gardens?
II. Design and Manufacturing: How to reconcile Real World and Digital World in PLM allowing multi-directional interoperability of the digital images of the same product between design-manufacturing?
III. Knowledge and Sentiment: How to consider both professional knowledge and crowd sentiments, trying to mediate extreme product-push and market-pull positions?
IV. Service-Oriented and Event-Driven: How to create a generic conceptual and implementation framework which could identify and implement the interoperability points between SOA and EDA in PLM value chain systems?
V. Business and Innovation: How to reconcile current profitable and competitive product-oriented business models with more intangible, risky, service-oriented and Internet-based businesses?
PSYMBIOSYS aims at improving the competitiveness of European Manufacturing industries by developing an innovative product-service engineering environment, symbolized by a five-pointed symbiosis star – design-production, product-service, knowledge-sentiment, EDA-SOA, business-innovation – and able to dramatically reduce the time-to-market of more attractive and sustainable product-service solutions. | [
"Products and Processes Engineering",
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
]
|
10.1002/hbm.23586 | Comparing functional MRI protocols for small, iron-rich basal ganglia nuclei such as the subthalamic nucleus at 7 T and 3 T | The basal ganglia (BG) form a network of subcortical nuclei. Functional magnetic resonance imaging (fMRI) in the BG could provide insight in its functioning and the underlying mechanisms of Deep Brain Stimulation (DBS). However, fMRI of the BG with high specificity is challenging, because the nuclei are small and variable in their anatomical location. High resolution fMRI at field strengths of 7 Tesla (T) could help resolve these challenges to some extent. A set of MR protocols was developed for functional imaging of the BG nuclei at 3 T and 7 T. The protocols were validated using a stop-signal reaction task (Logan et al. []: J Exp Psychol: Human Percept Perform 10:276–291). Compared with sub-millimeter 7 T fMRI protocols aimed at cortex, a reduction of echo time and spatial resolution was strictly necessary to obtain robust Blood Oxygen Level Dependent (BOLD) sensitivity in the BG. An fMRI protocol at 3 T with identical resolution to the 7 T showed no robust BOLD sensitivity in any of the BG nuclei. The results suggest that the subthalamic nucleus, as well as the substantia nigra, red nucleus, and the internal and external parts of the globus pallidus show increased activation in failed stop trials compared with successful stop and go trials. Hum Brain Mapp 38:3226–3248, 2017. | [
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W1814326336 | Closing Schemas in Object-Relational Databases | Schema closure is a property that guarantees that no schema component has external references, that is, references to components that are not included in the schema. In the context of object-relational databases, schema closure implies that types, tables and views do not have references to components that are not included in the schema. In order to achieve schema closure, in this work two basic approaches known as enlargement closure and reduction closure are proposed. Enlargement closure includes in the schema every referenced component. Reduction closure, on the other hand, is based on the transformation of the components that have external references, eliminating these references to fulfill schema closure. In this work, both closure approaches and the algorithms to carry out the closure in each of them are described. These algorithms generate and incorporate the needed components, whether being types or views, to reach the schema closure making easier therefore the definition of external schemas. Finally, to illustrate the concepts proposed in this work, we explain how to carry out schema closure in SQL:2008.KeywordsReduction ClosureObject TypeExternal ReferenceSchema ClosureObject ViewThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. | [
"Computer Science and Informatics"
]
|
W2154533423 | No Counterpart of Visual Perceptual Echoes in the Auditory System | It has been previously demonstrated by our group that a visual stimulus made of dynamically changing luminance evokes an echo or reverberation at ~10 Hz, lasting up to a second. In this study we aimed to reveal whether similar echoes also exist in the auditory modality. A dynamically changing auditory stimulus equivalent to the visual stimulus was designed and employed in two separate series of experiments, and the presence of reverberations was analyzed based on reverse correlations between stimulus sequences and EEG epochs. The first experiment directly compared visual and auditory stimuli: while previous findings of ~10 Hz visual echoes were verified, no similar echo was found in the auditory modality regardless of frequency. In the second experiment, we tested if auditory sequences would influence the visual echoes when they were congruent or incongruent with the visual sequences. However, the results in that case similarly did not reveal any auditory echoes, nor any change in the characteristics of visual echoes as a function of audio-visual congruence. The negative findings from these experiments suggest that brain oscillations do not equivalently affect early sensory processes in the visual and auditory modalities, and that alpha (8-13 Hz) oscillations play a special role in vision. | [
"Neuroscience and Disorders of the Nervous System"
]
|
647963 | The Hatha Yoga Project: Mapping Indian and Transnational Traditions of Physical Yoga through Philology and Ethnography | Hatha was the name given in medieval India to a method of yoga in which physical practices predominate. Its origins are unclear, but some of its techniques can be traced to the first millennium BCE and it gradually became central to several Indian religious traditions, including, by the second half of the second millennium CE, orthodox Hinduism. Hatha yoga is also the source of much of the modern yoga practised around the world today.
The history of hatha yoga is thus crucial for an understanding of both Indian religion and modern yoga, but is yet to be the object of serious study. As a result key questions about yoga — such as who were hatha yoga’s first practitioners and why did they practise it, and which modern yoga practices predate colonialism and which are innovations — are yet to be answered satisfactorily. The Hatha Yoga Project seeks to redress this by identifying the origins of both hatha and modern yoga. Its methodology will be predominantly philological and ethnographic, and it will draw on resources that are fast disappearing: crumbling manuscripts of Sanskrit texts on yoga and traditional Indian ascetic yogis whose practices are starting to change under the influence of modern globalised yoga.
The primary output of the project will be three monographs. The first will analyse hatha yoga and its practitioners in the period in which it was formalised, the 11th to 15th centuries CE. The second will document its subsequent proliferation and development, and identify what constituted yoga practice in India on the eve of colonialism. The third will focus on hatha yoga’s physical techniques in order to chart their history and identify continuities with and differences from the practices of modern globalised yoga. A secondary output will be critical editions and annotated translations of ten previously unpublished Sanskrit manuals of hatha yoga: the six earliest texts on the subject together with four later texts that were key to its subsequent development. | [
"The Study of the Human Past",
"Texts and Concepts"
]
|
10.1164/rccm.201203-0465PP | Malignant pleural effusion: Tumor-host interactions unleashed | Malignant pleural effusion (MPE) poses a significant clinical problem. Current nonetiologic management is suboptimal in terms of efficacy and safety. In light of recent research progress, we propose herein a new view of MPE development, which may rapidly translate into meaningful changes in therapeutics. In addition to tumor-induced impairment of pleural fluid drainage, pertinent findings point toward another pathway to MPE formation: a vicious loop of interactions between pleural-based tumor cells and the host vasculature and immune system that results in increased net fluid production via enhanced plasma extravasation into the pleural space. The ability of tumor cells to trigger this cascade likely rests on a specific and distinct transcriptional repertoire, which results in important vasoactive events in the pleural space. Although the characterization of tumor-derived factors responsible for MPE development is in the making, an additional, indirect path to MPE was recently demonstrated: tumor cells recruit and co-opt host cells and mediators, which, in turn, amplify tumor cell-primed fluid leakage and impact tumor cell functions. Importantly, recent evidence suggests that the biologic events that culminate in clinical MPE are likely amenable to therapeutic inhibition and even prevention. In this perspective, the scientific basis for an update of current concepts of MPE formation is highlighted. Key questions for future research are posed. Finally, a vision for novel, effective, safe, and convenient treatment modalities that can be offered to outpatients with MPE is set forth. | [
"Immunity, Infection and Immunotherapy",
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W4281788373 | Disentangling the Dynamics of VOCs and VOIs during the COVID-19 Pandemic in Peru using Bayesian Phylogenetics | Abstract At over 0.6% of the population, Peru has the highest SARS-CoV-2 mortality rate in the world. Much effort to sequence genomes was done in this country since mid-2020. However, an adequate analysis of the dynamics of the variants of concern and interest (VOCIs) is missing. We performed Bayesian phylodynamic analyses using different sampling approaches to determine the origin of the VOCIs in Peru, as well as their population dynamics. The COVID-19 pandemic in Peru was characterized by three waves. We showed that Lambda emerged in Peru during the first wave (April-July, 2020) but it did not reach high frequencies until the second wave. Alpha and Gamma were imported to Peru between the first and second waves (October-December, 2020). The gamma variant reached Peru from Brazil, whereas Alpha arrived at Peru from the United Kingdom. Effective population size (Ne) and effective reproductive number (Rt) suggest that Lambda, followed by Gamma, dominated the second wave of COVID-19 in Peru whereas Alpha was not very prevalent. During this wave, Lambda dominated all the Peruvian regions except the Northeast, where Gamma dominated. Migration patterns of Lambda and Gamma between the Northeast and other regions indicate that the different VOCI prevalence in the Northeast was not due to the isolation of this region. Also, during the second wave, Mu and Delta arrived in Peru (February-May, 2021) from the USA and the United Kingdom, respectively. Mu never reached high Rt nor Ne; on the other hand, at the final of the second wave, Delta showed Rt values higher than other VOCIs, beginning to increase its Ne and replacing Lambda and Gamma. Finally, Omicron reached Peru just before the beginning of the third wave (October-December, 2021) from the USA. Omicron had a high Rt since its arrival to Peru, originating new lineages and rapidly increasing its Ne which caused the third wave. In summary, we were able to determine important patterns of virus dynamics in Peru using Bayesian Phylogenetics. Besides, we demonstrated that Bayesian phylodynamics with a portion of the available genomes were sufficient to reconstruct the COVID-19 pandemic in Peru. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Mathematics",
"Environmental Biology, Ecology and Evolution"
]
|
10.1007/978-3-642-38856-9_22 | Interpolation Based Verification Of Floating Point Programs With Abstract Cdcl | One approach for smt solvers to improve efficiency is to delegate reasoning to abstract domains. Solvers using abstract domains do not support interpolation and cannot be used for interpolation-based verification. We extend Abstract Conflict Driven Clause Learning (acdcl) solvers with proof generation and interpolation. Our results lead to the first interpolation procedure for floating-point logic and subsequently, the first interpolation-based verifiers for programs with floating-point variables. We demonstrate the potential of this approach by verifying a number of programs which are challenging for current verification tools. | [
"Computer Science and Informatics"
]
|
10.1016/j.plantsci.2018.05.001 | Thioredoxin-mediated redox signalling in plant immunity | Activation of plant immune responses is associated with rapid production of vast amounts of reactive oxygen and nitrogen species (ROS/RNS) that dramatically alter cellular redox homeostasis. Even though excessive ROS/RNS accumulation can cause widespread cellular damage and thus constitute a major risk, plant cells have evolved to utilise these molecules as important signalling cues. Particularly their ability to modify redox-sensitive cysteine residues has emerged as a key mechanism to control the activity, conformation, protein-protein interaction and localisation of a growing number of immune signalling proteins. Regulated reversal of cysteine oxidation is dependent on activities of the conserved superfamily of Thioredoxin (TRX) enzymes that function as cysteine reductases. The plant immune system recruits specific TRX enzymes that have the potential to functionally regulate numerous immune signalling proteins. Although our knowledge of different TRX immune targets is now expanding, little remains known about how these enzymes select their substrates, what range of oxidized residues they target, and if they function selectively in different redox-mediated immune signalling pathways. In this review we discuss these questions by examining evidence showing TRX enzymes exhibit novel activities that play important roles in diverse aspects of plant immune signalling. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
CA 469505 A | AQUEOUS POLYURETHANE STOVING LACQUERS AND THE USE THEREOF FOR THE PRODUCTION OF LACQUER FILMS AND COATINGS | AQUEOUS POLYURETHANE STOVING LACQUERS AND THE USE THEREOF FOR THE PRODUCTION OF LACQUER FILMS AND COATINGS The present invention is directed to aqueous stoving lacquers containing pigments or fillers wherein the binders are based on combinations of (a) polyurethane prepolymers containing partly or completely neutralized carboxyl groups and blocked isocyanate groups and (b) polyurethane prepolymers containing free hydroxyl groups and partly or completely neutralized carboxyl groups. The binder components are further characterized by polyester and polyether segments, each being present in amounts of greater than 10% by weight. The present invention is also directed to films and coatings prepared from these aqueous stoving lacquers. | [
"Synthetic Chemistry and Materials",
"Materials Engineering"
]
|
10.1103/PhysRevB.98.195121 | Stability of the light-induced hidden charge density wave state within the phase diagram of 1 T-TaS2-xSex | The femtosecond transient optical spectroscopy is employed to study the relaxation dynamics of the equilibrium and hidden metastable charge-density-wave states in single crystals of 1T-TaS2-xSex as a function of the Se doping x. Similar to pristine 1T-TaS2, the transition to a hidden phase is observed at low temperature after a quench with a single 50 fs laser pulse, in the commensurate Mott phase up to x=0. 6. The photo-induced hidden-phase formation is accompanied by a notable change in the coherent phonon spectra, and particularly the collective amplitude mode. While the temperature stability of the hidden phase is only slightly dependent on the Se content, the creation-threshold fluence strongly increases with Se content from 1 to ∼4 mJ/cm2, which is attributed predominantly to the change in optical absorption coefficient at the laser excitation wavelength, and not an increased barrier of the hidden state with increasing Se. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
]
|
10.1111/rssb.12108 | The lasso for high dimensional regression with a possible change point | We consider a high dimensional regression model with a possible change point due to a covariate threshold and develop the lasso estimator of regression coefficients as well as the threshold parameter. Our lasso estimator not only selects covariates but also selects a model between linear and threshold regression models. Under a sparsity assumption, we derive non-asymptotic oracle inequalities for both the prediction risk and the (Formula presented. ) -estimation loss for regression coefficients. Since the lasso estimator selects variables simultaneously, we show that oracle inequalities can be established without pretesting the existence of the threshold effect. Furthermore, we establish conditions under which the estimation error of the unknown threshold parameter can be bounded by a factor that is nearly (Formula presented. ) even when the number of regressors can be much larger than the sample size n. We illustrate the usefulness of our proposed estimation method via Monte Carlo simulations and an application to real data. | [
"Mathematics",
"Computer Science and Informatics"
]
|
239781 | Legendrian contact homology and generating families | A contact structure on an odd dimensional manifold in a maximally non integrable hyperplane field. It is the odd dimensional counterpart of a symplectic structure. Contact and symplectic topology is a recent and very active area that studies intrinsic questions about existence, (non) uniqueness and rigidity of contact and symplectic structures. It is intimately related to many other important disciplines, such as dynamical systems, singularity theory, knot theory, Morse theory, complex analysis, ... Legendrian submanifolds are a distinguished class of submanifolds in a contact manifold, which are tangent to the contact distribution. These manifolds are of a particular interest in contact topology. Important classes of Legendrian submanifolds can be described using generating families, and this description can be used to define Legendrian invariants via Morse theory. Other the other hand, Legendrian contact homology is an invariant for Legendrian submanifolds, based on holomorphic curves. The goal of this research proposal is to study the relationship between these two approaches. More precisely, we plan to show that the generating family homology and the linearized Legendrian contact homology can be defined for the same class of Legendrian submanifolds, and are isomorphic. This correspondence should be established using a parametrized version of symplectic homology, being developed by the Principal Investigator in collaboration with Oancea. Such a result would give an entirely new type of information about holomorphic curves invariants. Moreover, it can be used to obtain more general structural results on linearized Legendrian contact homology, to extend recent results on existence of Reeb chords, and to gain a much better understanding of the geography of Legendrian submanifolds. | [
"Mathematics"
]
|
10.1007/s00209-014-1403-6 | On a conjecture of Gluck | Let (Formula presented. ) and (Formula presented. ) respectively denote the Fitting subgroup and the largest degree of an irreducible complex character of a finite group (Formula presented. ). A well-known conjecture of D. Gluck claims that if (Formula presented. ) is solvable then (Formula presented. ). We confirm this conjecture in the case where (Formula presented. ) is coprime to 6. We also extend the problem to arbitrary finite groups and prove several results showing that the largest irreducible character degree of a finite group strongly controls the group structure. | [
"Mathematics"
]
|
222593 | Fast iot market take-up through the things networks | The Things Industries (TTI) is a Dutch SME that focuses on the rise of the Internet of Things (IoT). The company expects that, upon the further expansion of the digital economy, a number of societal developments will greatly affect our daily life. Leading in all these developments will be in the domain of the IoT, which will gain a crucial place in the digital economy, based on the following fundamental ideas:
- The digital transformation of products: all products and services that can be made digital, smart or automated, will be. - The revolution of demand and offer: all traditional business models will be replaced by disruptive models.
- The inexhaustible need for data: the digital economy will have a continuously growing need for the collection, exchange and analysis of data.
TTI recently launched TTN, the first open, free-to-use IoT data network solution in the world, providing full coverage for the Amsterdam metropolitan region. Ever since, the network is being used successfully by companies and citizens of Amsterdam, and the first applications on this network have been developed and demonstrated. Currently, over 250 strong and active communities (60 within the EU) have set up local TTN-networks all over the world. TTI has established its current status with own funding, awards/prizes, subsidies, and profits from IoT/LoRaWAN gateway hardware sales and related consultancy. In order to expand exponentially, TTI will have to assess how to monetize its network and technology position optimally. The goal of this SMEInst proposal is to assess three different business models how to monetize its technology position through to scale up and growth.
Specific objectives in this H2020-SMEINT Phase 1 feasibility study are: - Explore promising business cases for TTI networks.
- Evaluate the required specifications and characteristics of these applications with potential partners, citizens, consumers and/or clients.
- Elaborate on a detailed business plan (D1). | [
"Computer Science and Informatics",
"Systems and Communication Engineering",
"Individuals, Markets and Organisations"
]
|
W2074307244 | Local government training in England and Wales, Denmark and Israel | This article highlights an interesting and often unduly neglected aspect of comparative public policy and administration: local government training. The argument advanced is that local government training based on the centrally focused model may tend to be: (i) skill-oriented and competence-framed; (ii) comprehensive; and (iii) quality-controlled in a relatively rigorous manner. By contrast, local government training based on the locally focused model may tend to be: (i) skill-oriented and competence-framed alongside a focus on ‘people’ and organizational issues, conventional policy issues and broad local government issues; (ii) non-comprehensive, and (iii) weakly controlled for quality. The integrative model, which is the most innovative form of the three models presented here, may tend to manifest a varied mix of the aforementioned features. Based on an institutional analysis combined with interviews with senior training officials at national and local levels, this argument is illustrated in England and... | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
US 2013/0034331 W | HONEYCOMB PAPER | A consolidated fibrous mat comprises 20 to 50 weight percent of reinforcing fibers; and a continuous phase connecting the reinforcing fibers, comprising 50 to 70 weight percent of a polymer having a melt temperature at least 20°C lower than the reinforcing fibers, and 5 to 10 weight percent of a binder having a melt temperature lower than the polymer; wherein the weight percent of each of the reinforcing fibers, the polymer, and the binder is based on the combined total weight of the reinforcing fibers, the polymer, and the binder. | [
"Materials Engineering",
"Synthetic Chemistry and Materials"
]
|
10.1126/sciadv.aat7052 | Crystal structure of rhodopsin in complex with a mini-Gosheds light on the principles of G protein selectivity | Selective coupling of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-Goprotein. The conformation of the receptor is identical to all previous structures of active rhodopsin, including the complex with arrestin. Thus, rhodopsin seems to adopt predominantly one thermodynamically stable active conformation, effectively acting like a “structural switch,” allowing for maximum efficiency in the visual system. Furthermore, our analysis of the well-defined GPCR–G protein interface suggests that the precise position of the carboxyl-terminal “hook-like” element of the G protein (its four last residues) relative to the TM7/helix 8 (H8) joint of the receptor is a significant determinant in selective G protein activation. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences"
]
|
10.1002/jimd.12061 | Ammonia and autophagy: An emerging relationship with implications for disorders with hyperammonemia | (Macro)autophagy/autophagy is a highly regulated lysosomal degradative process by which cells recycle their own nutrients, such as amino acids and other metabolites, to be reused in different biosynthetic pathways. Ammonia is a diffusible compound generated daily from catabolism of nitrogen-containing molecules and from gastrointestinal microbiome. Ammonia homeostasis is tightly controlled in humans and ammonia is efficiently converted by the healthy liver into non-toxic urea (through ureagenesis) and glutamine (through glutamine synthetase). Impaired ammonia detoxification leads to systemic hyperammonemia, a life-threatening condition resulting in detrimental effects on central nervous system. Here, we review current understanding on the role of ammonia in modulation of autophagy and the potential implications in the pathogenesis and treatment of disorders with hyperammonemia. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
W2108375716 | Managing Transboundary Crises: Identifying the Building Blocks of an Effective Response System | In recent years, crises have become increasingly transboundary in nature. This exploratory paper investigates whether and how the transboundary dimensions of crises such as pandemics, cyber attacks and prolonged critical infrastructure failure accentuate the challenges that public and private authorities confront in the face of urgent threats. We explore the transboundary dimensions of crises and disasters, discuss how an increase in ‘transboundedness’ affects traditional crisis management challenges and investigate what administrative mechanisms are needed to deal with these compounded challenges. Building on lessons learned from past crises and disasters, our goal is to stimulate a discussion among crisis management scholars about the political-administrative capabilities required to deal with ‘transboundary’ crises. | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.1016/j.drudis.2014.06.024 | Factor XII: A drug target for safe interference with thrombosis and inflammation | Data from experimental animal models revealed an essential role for factor XII (FXII) in thrombotic occlusive diseases. In contrast to other blood coagulation factors, deficiency in the protease is not associated with abnormal bleeding from injury sites (hemostasis) in patients or in animals. Cumulatively, these findings suggest that FXII could be targeted as a new method of anticoagulation that is devoid of bleeding risks. An FXIIa-neutralizing antibody, 3F7, has been developed that inhibited thrombosis in an extracorporeal membrane oxygenation (ECMO) system as efficiently as heparin. However, in sharp contrast to heparin, 3F7 treatment was not associated with an increase in therapy-associated hemorrhage. In this review, we summarize current knowledge of FXII physiology and pharmacology. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W2069103798 | Association between psychological distress and a sense of contribution to society in the workplace | Globally, mental health promotion related to psychological distress in the workplace has become a great concern, and a focus of much research attention. However, a sense of contribution to society and sense of bonding with the workplace have not been examined in relation to psychological distress. Thus, the purpose of this study is to examine whether these two factors are associated with psychological distress.We conducted a cross-sectional survey of 1137 full-time employees who worked in systems engineering, sales, or administration at a Japanese company. Participant's sense of contribution to society, sense of bonding with the workplace, psychological distress, and qualitative job stress (quantitative and qualitative workloads, job-control latitude, and support from supervisors, co-workers and family) were assessed with a questionnaire. We performed multiple logistic regression analyses to examine associations between psychological distress and sense of contribution to society and of bonding with the workplace.A high sense of contribution to society was significantly associated with a high sense of bonding with the workplace (Spearman's ρ = 0.47, p < 0.01). A sense of contribution to society was negatively associated with psychological distress after adjusting for job stress factors (OR = 2.05, 95% CI 0.99-4.23) or sociodemographic characteristics of participants (OR = 2.92, 1.53-5.59). After adjusting for job stress factors as well as sociodemographic characteristics, the association became weaker. A sense of bonding with the workplace was negatively associated with psychological distress after adjusting for sociodemographic characteristics (OR = 2.49, 1.29-4.79). However, this association was not observed after adjusting for job stress factors.Psychological distress in the workplace was associated with sense of contribution to society. Therefore, workplace mental health promotion should consider the workers' sense of contribution to society. | [
"The Human Mind and Its Complexity",
"The Social World and Its Interactions",
"Individuals, Markets and Organisations"
]
|
215933 | Trusted online service for identity assurance | The objective of the overall innovation project is to commercialize a trusted online service for identity assurance (IDAaaS -
Identity Assurance as a Service). This service will be implemented according to European standards for electronic identity,
including eIDAS and STORK. The new service will be based on several years of development of secure electronic identity
and digital signatures in the Nordic market.
The expected outcome will be a simplified and cost effective online service for identity assurance that can be used in
regulated industries such as banks and financial institutions (hereafter referred to as banks). The purpose of the service will
be to assure that a user is who she claims to be when signing up to a new online service.
The lack of good solutions for trusted digital on-boarding of customers makes it difficult for new online-only players to enter
the market, which could otherwise increase competition and improve the bank services in general. Large costs, trouble and
hassle for both the bank client and the bank hamper innovation in the finance sector.
Electronic identity is a prerequisite for digital on-boarding. The electronic identity in Europe is fragmented and the missing
implementation of European standards in this field represents a major barrier to secure cross-country transactions. The
problem of establishing the true identity of the onboarding customer must be solved using multiple tools and instruments.
This tool box of multiple tools is the innovation of Signicat’s solution. | [
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
]
|
W2009754871 | Timeliness of care and prognosis in patients with lung cancer | Timeliness of care is an important dimension of health care quality. The determining factors of less timely care and their influence on the survival of patients with lung cancer (LC) remain uncertain.To analyse the delays in the diagnosis and treatment of LC in our health area, the factors associated with the timeliness of care and their possible relationship with the survival of these patients.A retrospective study was conducted on all patients with a cytohistologically confirmed diagnosis of LC between 1 June 2005 and 31 May 2008. The time delays for consultation (specialist delay), diagnosis (diagnosis delay), and treatment (treatment delay), were analysed, as well as the factors associated with these delays and the influence of the timeliness of care on survival.A total of 307 cases were included (87 % males). The mean specialist delay was 53.6 days (median 35 days), diagnosis delay 31.5 days (median 18 days), treatment delay 23.5 days (median 14 days). The greater age of the patient and a more advanced stage were associated with a shorter specialist delay. Male sex, a more advanced stage, and poor general status were associated with a shorter treatment delay. The survival is longer in patients with a longer treatment delay.The delay in the diagnosis in our population seems to be excessively long. The greater the age, a more advanced tumour stage, male sex, and poor general health status are associated with shorter delays. A longer treatment delay is associated with a longer survival. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
]
|
10.1101/gad.2036411 | The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity | Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 a (HP1a) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions. Loss of Dek in Drosophila leads to a Su(var) phenotype and global reduction in heterochromatin. Thus, these findings show that DEK is a key factor in maintaining the balance between heterochromatin and euchromatin in vivo. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
W2056162906 | The Dry Valley Lakes, Antarctica: from sulfur stains on Earth to sulfur stains in the Jovian system | Most organisms dwell in what we consider to be normal environments, while others, which are called extremophiles,
may thrive in harsher conditions. These living organisms are mainly of unicellular (both prokaryotes and, to a lesser
extent, there are some eukaryotes) But the extremophiles also include multicellular organisms, including worms, insects
and crustaceans. In the present work we survey specific extremophiles in some detail. Astrobiology is concerned with all
of these extremophiles, as they may be models for extant life in similar environments elsewhere in the universe. In the
more restricted search for life through exploration of the Solar System, the main focus is on the preparation of suites of
experiments that may attempt to discover the habitability of planets and their satellites. In this context we ask ourselves:
What biosignatures can facilitate life detection, both unicellular and multicellular, in extreme environments? The
environments that are within reach of present and future space missions include the Jupiter satellite Europa. The icecovered
lakes of Antarctica's McMurdo Dry Valleys have long been of interest to astrobiology. These environments
harbor unique microbial ecosystems that could orient us how to plan our experiments on Europa. | [
"Universe Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Earth System Science"
]
|
10.1039/d0nr00868k | Size-dependent aggregation of hydrophobic nanoparticles in lipid membranes | Aggregation of hydrophobic spherical nanoparticles in lipid membranes depends on nanoparticle size. Nanoparticles of ∼3 nm sense and induce membrane curvature. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
]
|
259527 | ANALYTIC PROPERTIES OF INFINITE GROUPS:
limits, curvature, and randomness | The overall goal of this project is to develop new concepts and techniques in geometric and asymptotic group theory for a systematic study of the analytic properties of discrete groups. These are properties depending on the unitary representation theory of the group. The fundamental examples are amenability, discovered by von Neumann in 1929, and property (T), introduced by Kazhdan in 1967.
My main objective is to establish the precise relations between groups recently appeared in K-theory and topology such as C*-exact groups and groups coarsely embeddable into a Hilbert space, versus those discovered in ergodic theory and operator algebra, for example, sofic and hyperlinear groups. This is a first ever attempt to confront the analytic behavior of so different nature. I plan to work on crucial open questions: Is every coarsely embeddable group C*-exact? Is every group sofic? Is every hyperlinear group sofic?
My motivation is two-fold:
- Many outstanding conjectures were recently solved for these groups, e.g. the Novikov conjecture (1965) for coarsely embeddable groups by Yu in 2000 and the Gottschalk surjunctivity conjecture (1973) for sofic groups by Gromov in 1999. However, their group-theoretical structure remains mysterious.
- In recent years, geometric group theory has undergone significant changes, mainly due to the growing impact of this theory on other branches of mathematics. However, the interplay between geometric, asymptotic, and analytic group properties has not yet been fully understood.
The main innovative contribution of this proposal lies in the interaction between 3 axes: (i) limits of groups, in the space of marked groups or metric ultralimits; (ii) analytic properties of groups with curvature, of lacunary or relatively hyperbolic groups; (iii) random groups, in a topological or statistical meaning. As a result, I will describe the above apparently unrelated classes of groups in a unified way and will detail their algebraic behavior. | [
"Mathematics"
]
|
GB 0105206 W | SUPPORTING BRACKET ASSEMBLY FOR A HORIZONTAL LIFELINE CABLE | A supporting bracket assembly for a horizontal lifeline cable (4) comprises a base plate (14), bracket means (24) and holding means (28) for the cable. The base plate (14) is provided for securing to a structure (6). The bracket means (24) is secured to the base plate and adapted for frictionally restrained pivotability with respect to the base plate and the holding means (28) for the cable (4) is secured to the bracket means (24). In this way, dynamic loading of the cable (4) results in pivoting of the bracket means (24), against frictional restraint, from a first position (36) into a second position (38). | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
306484 | Implicit Programming | I propose implicit programming, a paradigm for developing reliable software using new programming language specification constructs and tools, supported through the new notion of software synthesis procedures. The paradigm will enable developers to use specifications as executable programming language constructs and will automate some of the program construction tasks to the point where they become feasible for the end users. Implicit programming will increase developer productivity by enabling developers to focus on the desired software functionality instead of worrying about low-level implementation details. Implicit programming will also improve software reliability, because the presence of specifications will make programs easier to analyze.
From the algorithmic perspective, I propose a new agenda for research in algorithms for decidable logical theories. An input to such an algorithm is a logical formula (or a boolean-valued programming language expressions). Whereas a decision procedure for satisfiability merely checks whether there exists a satisfying assignment for the formula, we propose to develop synthesis procedures. A synthesis procedure views the input as a relation between inputs and outputs, and produces a function from input variables to output variables. In other words, it transforms a specification into a computable function. We will design synthesis procedures for important classes of formulas motivated by useful programming language fragments. We will use synthesis procedures as a compilation mechanism for declarative programming language constructs, ensuring correctness by construction. To develop practical synthesis procedures we will combine insights from decision procedure research (including the results on SMT solvers), with the research on compiler construction, program analysis, and program transformation. The experience from the rich model toolkit initiative (http://RichModels.org) will help us address these goals. | [
"Computer Science and Informatics"
]
|
10.1002/2014JB011850 | Experiments of dike-induced deformation: Insights on the long-term evolution of divergent plate boundaries | The shallow transport of magma occurs through dikes causing surface deformation. Our understanding of the effects of diking at the surface is limited, especially on the long term, for repeated intrusive episodes. We use analogue models to study the upper crustal deformation induced by dikes. We insert metal plates within cohesive sand with three setups: in setup A, the intrusion rises upward with constant thickness and in setups B and C, the intrusion thickens at a fixed depth, with final rectangular (setup B) or triangular (setup C) shape in section. Setup A creates a doming delimited by reverse faults, with secondary apical graben, without close correspondence in nature. In setups B and C, a depression flanked by two uplifted areas is bordered by inward dipping normal faults propagating downward and, for deeper intrusions in setup B, also by inner faults, reverse at the surface; this deformation is similar to what is observed in nature, suggesting a consistent physical behavior. Dikes in nature initially propagate developing a mode I fracture at the tip, subsequently thickened by magma intrusion, without any host rock translation in the propagation direction (as in setup A). The deformation pattern in setups B and C depends on the intrusion depth and thickness, consistently to what is observed along divergent plate boundaries. The early deformation in setups B and C is similar to that from a single rifting episode (i. e. , Lakagigar, Iceland, and Dabbahu, Afar), whereas the late stages resemble the structure of mature rifts (i. e. , Krafla, Iceland), confirming diking as a major process in shaping divergent plate boundaries. | [
"Earth System Science"
]
|
W2591061288 | The Online Transportation Network in Indonesia: A Pendulum between the Sharing Economy and Ex Ante Regulation | The prominent role of innovation in the emerging digital market in Indonesia presents new challenges for current competition law and policy. Traditionally reliant on market definition for the analysis, the present competition law may not yet have sufficiently taken innovation into consideration. In the competition policy area, while innovation has not taken a clear role in tailoring suitable regulations or approaches, markets have attempted to adapt themselves to the new changes in order to meet rising demand. The present state of policy is illustrated by the development oj online transportation networks like those provided by Uber and GrabCar, services similar to those that have been traditionally offered by taxi companies. While regulation asymmetry has been accused of not allowing a level playing field for conventional taxis versus online transportation networks, the concept of the sharing economy seems to address today's policy approach in Indonesia, which favors ex ante regulation on public transportation service provision in the country. This paper examines the applicable regulations in the transportation network industry and discusses how competition policy might cope with this issue and in what cases competition law might deal with innovation brought by online transportation network in the public transportation industry in Indonesia. | [
"Institutions, Governance and Legal Systems",
"Individuals, Markets and Organisations"
]
|
10.1007/s10519-013-9628-4 | Three-and-a-half-factor model? the genetic and environmental structure of the CBCL/6-18 internalizing grouping | In the present article, multivariate genetic item analyses were employed to address questions regarding the ontology and the genetic and environmental etiology of the Anxious/Depressed, Withdrawn, and Somatic Complaints syndrome dimensions of the Internalizing grouping of the Child Behavior Checklist/6-18 (CBCL/6-18). Using common and independent pathway genetic factor modeling, it was examined whether these syndrome dimensions can be ascribed a realist ontology. Subsequently, the structures of the genetic and environmental influences giving rise to the observed symptom covariation were examined. Maternal ratings of a population-based sample of 17,511 Dutch twins of mean age 7. 4 (SD = 0. 4) on the items of the Internalizing grouping of the Dutch CBCL/ 6-18 were analyzed. Applications of common and independent pathway modeling demonstrated that the Internalizing syndrome dimensions may be better understood as a composite of unconstrained genetic and environmental influences than as causally relevant entities generating the observed symptom covariation. Furthermore, the results indicate a common genetic basis for anxiety, depression, and withdrawn behavior, with the distinction between these syndromes being driven by the individual-specific environment. Implications for the substantive interpretation of these syndrome dimensions are discussed. | [
"Integrative Biology: from Genes and Genomes to Systems",
"The Human Mind and Its Complexity"
]
|
10.1109/JESTPE.2017.2688454 | Linearized Modeling Methods Of Ac Dc Converters For An Accurate Frequency Response | Wideband harmonics and resonances are challenging the stability and power quality of emerging power-electronic-based power systems, and therefore, harmonic modeling and analysis of power converters are becoming even more important. However, the complex interactions on both ac and dc sides of a converter and the propagated interaction to other systems have been a challenging task for modeling. This paper introduces a systematic overview of different linearized modeling methods. It is followed by a step-by-step elaboration of the underlying principles of different methods, and practical difficulties in modeling are discussed. A comparison of these methods is presented. Simulation results show that the harmonic state-space modeling method provides an efficient way to analyze both steady-state frequency coupling and dynamic harmonic interactions in power-electronic-based power systems. | [
"Systems and Communication Engineering",
"Products and Processes Engineering"
]
|
W2043568647 | Spectroscopic and Computational Characterization of Substrate-Bound Mouse Cysteine Dioxygenase: Nature of the Ferrous and Ferric Cysteine Adducts and Mechanistic Implications | Cysteine dioxygenase (CDO) is a mononuclear non-heme Fe-dependent dioxygenase that catalyzes the initial step of oxidative cysteine catabolism. Its active site consists of an Fe(II) ion ligated by three histidine residues from the protein, an interesting variation on the more common 2-His-1-carboxylate motif found in many other non-heme Fe(II)-dependent enzymes. Multiple structural and kinetic studies of CDO have been carried out recently, resulting in a variety of proposed catalytic mechanisms; however, many open questions remain regarding the structure/function relationships of this vital enzyme. In this study, resting and substrate-bound forms of CDO in the Fe(II) and Fe(III) states, both of which are proposed to have important roles in this enzyme's catalytic mechanism, were characterized by utilizing various spectroscopic methods. The nature of the substrate/active site interactions was also explored using the cysteine analogue selenocysteine (Sec). Our electronic absorption, magnetic circular dichroism, and resonance Raman data exhibit features characteristic of direct S (or Se) ligation to both the high-spin Fe(II) and Fe(III) active site ions. The resulting Cys- (or Sec-) bound species were modeled and further characterized using density functional theory computations to generate experimentally validated geometric and electronic structure descriptions. Collectively, our results yield a more complete description of several catalytically relevant species and provide support for a reaction mechanism similar to that established for many structurally related 2-His-1-carboxylate Fe(II)-dependent dioxygenases. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1074/jbc.R112.420752 | The mitochondrial calcium uniporter (MCU): Molecular identity and physiological roles | The direct measurement of mitochondrial [Ca2+] with highly specific probes demonstrated that major swings in organellar [Ca2+] parallel the changes occurring in the cytosol and regulate processes as diverse as aerobic metabolism and cell death by necrosis and apoptosis. Despite great biological relevance, insight was limited by the complete lack of molecular understanding. The situation has changed, and new perspectives have emerged following the very recent identification of the mitochondrial Ca2+ uniporter, the channel allowing rapid Ca2+ accumulation across the inner mitochondrial membrane. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
10.1038/s41561-020-0623-0 | Coupled Southern Ocean cooling and Antarctic ice sheet expansion during the middle Miocene | The middle Miocene climate transition (~14 million years ago) was characterized by a dramatic increase in the volume of the Antarctic ice sheet. The driving mechanism of this transition remains under discussion, with hypotheses including circulation changes, declining carbon dioxide in the atmosphere and orbital forcing. Southern Ocean records of planktic foraminiferal Mg/Ca have previously been interpreted to indicate a cooling of 6–7 °C and a decrease in salinity that preceded Antarctic cryosphere expansion by up to ~300,000 years. This interpretation has led to the hypothesis that changes in meridional heat and vapour transport along with an early thermal isolation of Antarctica from extrapolar climates played a fundamental role in triggering ice growth. Here we revisit the middle Miocene Southern Ocean temperature evolution using clumped isotope and lipid biomarker temperature proxies. Our records indicate that the Southern Ocean cooling and the associated salinity decrease occurred in phase with the expansion of the Antarctic ice sheet. We demonstrate that the timing and magnitude of the Southern Ocean temperature change seen in previous reconstructions can be explained if we consider pH as an additional, non-thermal, control on foraminiferal Mg/Ca ratios. Therefore, our new dataset challenges the view of a thermal isolation of Antarctica preceding ice sheet expansion, and suggests a strong coupling between Southern Ocean conditions and Antarctic ice volume in times of declining atmospheric carbon dioxide. | [
"Earth System Science"
]
|
10.1186/s12968-015-0174-5 | 4D flow cardiovascular magnetic resonance consensus statement | Abstract Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1. 5×1. 5×1. 5 - 3×3×3 mm<sup>3</sup>, typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations. | [
"Products and Processes Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Systems and Communication Engineering",
"Physiology in Health, Disease and Ageing"
]
|
W2025045283 | Assessing the Allocation of CDBG to Community Development Need | This article evaluates how well the current allocation formula for the Community Development Block Grant (CDBG) program allocates funds with respect to community development need. We assemble an index of community development need from a variety of demographic and economic indicators which capture the components of need that can be addressed directly by the CDBG program based on its statutory objectives. We use this index to estimate the relation between funding levels and community development need and how this relation has changed over time. In particular, we assess the effectiveness of targeting by examining the horizontal and vertical equity of the formula. Results suggest that the relation between the formula data inputs and community development need has deteriorated over the past two decades. The present formula is shown to underfund Formula A grantees conditional on need and to overfund a select number of high-income, slow-growth, older communities. Finally, we consider several alternative formula... | [
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems"
]
|
W2025877554 | MEASUREMENT AND SIMULATION OF EQUATORIAL IONOSPHERIC PLASMA BUBBLES TO ASSESS THEIR IMPACT ON GNSS PERFORMANCE | Ionospheric anomaly is one of the major error sources which deteriorate the GNSS performance. In the equatorial region, effects of the ionospheric plasma bubbles are of great interest because they are pretty common phenomena, especially in the period of the high solar activity. In order to evaluate the GNSS performance under circumstance of the bubbles, an ionospheric scintillation monitor has been developed and installed in Bangkok, Thailand. Furthermore, a model simulating the ionospheric delay and scintillation due to the bubbles has been developed. Based on these developments, the effects of the simulated plasma bubbles are analyzed and their agreement with the real observation is demonstrated. An availability degradation of the GPS ground based augmentation system (GBAS) caused by the bubbles is exampled in details. Finally, an integrated GPS/INS approach based on the Doppler frequency is proposed to remedy the deterioration. | [
"Systems and Communication Engineering",
"Earth System Science"
]
|
10.1111/j.1365-2745.2012.02001.x | Strong persistent growth differences govern individual performance and population dynamics in a tropical forest understorey palm | Persistent variation in growth rate between individual plants can have strong effects on population dynamics as fast growers reach the reproductive size at an earlier age and thus potentially contribute more to population growth than slow growers. In tropical forests, such persistent growth differences have so far been documented for canopy tree species, where they are primarily associated with forest gap dynamics, but not for forest understorey species which are less responsive to gaps. Here, we study persistent growth differences and their demographic consequences for a tropical forest understorey palm, Chamaedorea elegans. We measured internodes along stems and annual leaf production rates to reconstruct lifetime growth trajectories. Using regression analysis, we determined the relative effect of stem length and past growth rate on vital rates (survival, growth and reproduction). We then simulated population dynamics using integral projection models (IPMs), in which individuals were categorized by both stem length and lifetime past growth rate. Stem growth differences among individual palms persisted over most of their lifetime. Past growth rate averaged over the palm's lifetime proved to be a very good predictor of growth, reproduction probability and seed production, often much better than stem length or age. The effects of past growth rate were positive, indicating that fast growers maintain high rates of growth and reproduction. Projected population growth rate (λ) was 1. 056, and stable stage distributions closely resembled observed population structures. Separating individuals with above-median and below-median past growth rates in IPMs revealed substantial differences in elasticity values. The 50% fastest growers had a 1. 8 times higher elasticity, and thus a 1. 8 times higher contribution to population growth, compared to slow growers. Synthesis. Strong and persistent growth differences that are probably associated with environmental (edaphic) and/or genetic factors govern individual performance and population dynamics of a tropical forest understorey palm. Overall, our study shows that strong inter-individual growth variation is not limited to canopy trees and that it can be generated by other factors than canopy dynamics. It is likely that persistently fast-growing 'super performers' govern population growth of many long-lived species. Differences in performance between individuals have important but largely unknown demographic implications. We detected strong and persistent growth differences between individual palms. Population models showed that fast growers contributed twice as much to population growth compared to slow growers. This illustrates the key role of fast growers in plant population dynamics. | [
"Environmental Biology, Ecology and Evolution"
]
|
10.1261/rna.060442.116 | Understanding in-line probing experiments by modeling cleavage of nonreactive RNA nucleotides | Ribonucleic acid (RNA) is involved in many regulatory and catalytic processes in the cell. The function of any RNA molecule is intimately related with its structure. In-line probing experiments provide valuable structural data sets for a variety of RNAs and are used to characterize conformational changes in riboswitches. However, the structural determinants that lead to differential reactivities in unpaired nucleotides have not been investigated yet. In this work, we used a combination of theoretical approaches, i. e. , classical molecular dynamics simulations, multiscale quantum mechanical/molecular mechanical calculations, and enhanced sampling techniques in order to compute and interpret the differential reactivity of individual residues in several RNA motifs, including members of the most important GNRA and UNCG tetraloop families. Simulations on the multinanosecond timescale are required to converge the related free-energy landscapes. The results for uGAAAg and cUUCGg tetraloops and double helices are compared with available data from in-line probing experiments and show that the introduced technique is able to distinguish between nucleotides of the uGAAAg tetraloop based on their structural predispositions toward phosphodiester backbone cleavage. For the cUUCGg tetraloop, more advanced ab initio calculations would be required. This study is the first attempt to computationally classify chemical probing experiments and paves the way for an identification of tertiary structures based on the measured reactivity of nonreactive nucleotides. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1016/j.neuron.2016.02.033 | Membrane Lipids in Presynaptic Function and Disease | Lipids are the most abundant organic compounds in the brain. The brain has a unique lipidome, and changes in lipid concentration, organization, and metabolism are associated with many neuronal diseases. Here, we discuss recent advances in understanding presynaptic membrane lipid organization, centered on illustrative examples of how the lipids themselves regulate membrane trafficking and control protein activity. This insight highlights that presynaptic terminals are membrane-remodeling machines and that cooperation between lipid and protein molecules underlies presynaptic activity. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
EP 81107405 A | Spreader vehicle for solid and liquid thawing materials. | Streufahrzeug (1) mit Streuvorrichtungen und je einem Behälter (2, 3) für granulierte und flüssige Taustoffe, mit der die granulierten und die flüssigen Taustoffe wahlweise jeweils separat oder gemischt über eine maximale Streubreite von ca. 25 m als auch in beliebig schmaleren Streubreiten mit gleicher oder unterschiedlicher Streudichte ausgestreut werden können. Im Behälter (3) des granulierten Taustoffes sind drei in Längsrichtung des Fahrzeuges verlaufende Endlosförderer (9, 10, 11) angeordnet. Jeder Endlosförderer (9, 10, 11) ist mit einer Streuvorrichtung (16, 26, 27) verbunden, deren Streusteller (28) auch aus dem Flüssigkeitsbehälter (2) durch e eine Zufuhrleitung (44, 44', 44") mittels separater Flüssigkeitspumpen (45, 46, 47) der flüssige Taustoff zugeführt werden kann. Die Endlosförder (9, 10,11) und die die Flüssigkeitspumpen (45, 46, 47) separat antreibenden Hydraulikmotoren (12, 13, 14) bzw. (86, 87, 88) sind mittels einer Streuvorrichtung auf fahrgeschwindigkeitsproportionale und auf wählbare Streudichten einstellbare Streumengen streubar, und die Hydraulikmotoren (36/1, 36/2, 36/2) sind bezüglich ihrer die Streuweite bestimmenden Drehzahl einstellbar. Zwei Streuvorrichtungen (26, 27) sind außerhalb der Umrißlinie des Streufahrzeuges (1) angeordnet und durch zwei zur Fahrzeuglängsachse (5) verlaufende Endlosförderer (22, 23) mit den Endlosförderern (9, 11) des Behälters (3) verbunden. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
615709 | Understanding evolutionary rates on the Tree of Life in time and space | According to models of adaptive radiation and sexual selection trait divergence is a key step in the speciation process. At a macroevolutionary scale this leads to the prediction that speciation is driven by the rate of trait evolution rather than the state of the trait. Despite the established theoretical links between trait evolution and speciation, most macroevolutionary studies focus on predicting speciation as a state dependent process. To date the hypothesis that rapid speciation is driven by rapid trait evolution has rarely been tested. If the rate or degree of divergence in species traits is an important factor in driving differences in speciation rates among lineages then there must also be variation in rates of trait evolution among lineages. Using my recently completed phylogeny of all extant birds, novel datasets of ecomorphological and secondary sexual traits, and computer simulations, I will carry out the first large-scale analyses to determine the extent to which rates of phenotypic evolution vary among lineages and across space, test the causes of non-constant evolutionary rates, and derive and test predictions on the effects of rates of trait evolution on speciation. | [
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1038/s41380-018-0321-0 | Big data approaches to decomposing heterogeneity across the autism spectrum | Autism is a diagnostic label based on behavior. While the diagnostic criteria attempt to maximize clinical consensus, it also masks a wide degree of heterogeneity between and within individuals at multiple levels of analysis. Understanding this multi-level heterogeneity is of high clinical and translational importance. Here we present organizing principles to frame research examining multi-level heterogeneity in autism. Theoretical concepts such as ‘spectrum’ or ‘autisms’ reflect non-mutually exclusive explanations regarding continuous/dimensional or categorical/qualitative variation between and within individuals. However, common practices of small sample size studies and case–control models are suboptimal for tackling heterogeneity. Big data are an important ingredient for furthering our understanding of heterogeneity in autism. In addition to being ‘feature-rich’, big data should be both ‘broad’ (i. e. , large sample size) and ‘deep’ (i. e. , multiple levels of data collected on the same individuals). These characteristics increase the likelihood that the study results are more generalizable and facilitate evaluation of the utility of different models of heterogeneity. A model’s utility can be measured by its ability to explain clinically or mechanistically important phenomena, and also by explaining how variability manifests across different levels of analysis. The directionality for explaining variability across levels can be bottom-up or top-down, and should include the importance of development for characterizing changes within individuals. While progress can be made with ‘supervised’ models built upon a priori or theoretically predicted distinctions or dimensions of importance, it will become increasingly important to complement such work with unsupervised data-driven discoveries that leverage unknown and multivariate distinctions within big data. A better understanding of how to model heterogeneity between autistic people will facilitate progress towards precision medicine for symptoms that cause suffering, and person-centered support. | [
"Neuroscience and Disorders of the Nervous System",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
]
|
10.1063/1.4737646 | Light Sailboats Laser Driven Autonomous Microrobots | We introduce a system of light driven microscopic autonomous moving particles that move on a flat surface. The design is simple, yet effective: Micrometer sized objects with wedge shape are produced by photopolymerization, and they are covered with a reflective surface. When the area of motion is illuminated perpendicularly from above, the light is deflected to the side by the wedge shaped objects, in the direction determined by the position and orientation of the particles. The momentum change during reflection provides the driving force for an effectively autonomous motion. The system is an efficient tool to study self propelled microscopic robots. | [
"Synthetic Chemistry and Materials",
"Materials Engineering",
"Condensed Matter Physics"
]
|
10.1088/1475-7516/2019/11/017 | Reconstructing The Spectral Shape Of A Stochastic Gravitational Wave Background With Lisa | We present a set of tools to assess the capabilities of LISA to detect and reconstruct the spectral shape and amplitude of a stochastic gravitational wave background (SGWB) . We first provide the LISA power-law sensitivity curve and binned power-law sensitivity curves, based on the latest updates on the LISA design. These curves are useful to make a qualitative assessment of the detection and reconstruction prospects of a SGWB . For a quantitative reconstruction of a SGWB with arbitrary power spectrum shape, we propose a novel data analysis technique: by means of an automatized adaptive procedure, we conveniently split the LISA sensitivity band into frequency bins, and fit the data inside each bin with a power law signal plus a model of the instrumental noise. We apply the procedure to SGWB signals with a variety of representative frequency profiles, and prove that LISA can reconstruct their spectral shape. Our procedure, implemented in the code SGWBinner, is suitable for homogeneous and isotropic SGWBs detectable at LISA, and it is also expected to work for other GW observatories. | [
"Universe Sciences",
"Fundamental Constituents of Matter",
"Computer Science and Informatics"
]
|
10.1038/ncomms15736 | Water pumping in mantle shear zones | Water plays an important role in geological processes. Providing constraints on what may influence the distribution of aqueous fluids is thus crucial to understanding how water impacts Earth's geodynamics. Here we demonstrate that ductile flow exerts a dynamic control on water-rich fluid circulation in mantle shear zones. Based on amphibole distribution and using dislocation slip-systems as a proxy for syn-tectonic water content in olivine, we highlight fluid accumulation around fine-grained layers dominated by grain-size-sensitive creep. This fluid aggregation correlates with dislocation creep-accommodated strain that localizes in water-rich layers. We also give evidence of cracking induced by fluid pressure where the highest amount of water is expected. These results emphasize long-term fluid pumping attributed to creep cavitation and associated phase nucleation during grain size reduction. Considering the ubiquitous process of grain size reduction during strain localization, our findings shed light on multiple fluid reservoirs in the crust and mantle. | [
"Earth System Science",
"Condensed Matter Physics"
]
|
10.1021/jacs.8b11752 | Base-Promoted, Remote C-H Activation at a Cationic (n <sup>5</sup> -C <inf>5</inf> Me <inf>5</inf> )Ir(III) Center Involving Reversible C-C Bond Formation of Bound C <inf>5</inf> Me <inf>5</inf> | C-H bond activation at cationic [(n 5 -C 5 Me 5 )Ir(PMe 2 Ar′)] centers is described, where PMe 2 Ar′ are the terphenyl phosphine ligands PMe 2 Ar Xyl2 and PMe 2 Ar Dipp2 . Different pathways are defined for the conversion of the five-coordinate complexes [(n 5 -C 5 Me 5 )IrCl(PMe 2 Ar′)] + , 2(Xyl) + and 2(Dipp) + , into the corresponding pseudoallyls 3(Xyl) + and 3(Dipp) + . In the absence of an external Brønsted base, electrophilic, remote ζ C-H activation takes place, for which the participation of dicationic species, [(n 5 -C 5 Me 5 )Ir(PMe 2 Ar′)] 2+ , is proposed. When NEt 3 is present, the PMe 2 Ar Dipp2 system is shown to proceed via 4(Dipp) + as an intermediate en route to the thermodynamic, isomeric product 3(Dipp) + . This complex interconversion involves a non-innocent C 5 Me 5 ligand, which participates in C-H and C-C bond formation and cleavage. Remarkably, the conversion of 4(Dipp) + to 3(Dipp) + also proceeds in the solid state. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
758427 | Novel Blueprints for the Visible-Light-Mediated Assembly of C–N Bonds via Nitrogen Radicals | Nitrogen-containing compounds underpin every aspect of our daily life as they form the structural basis of almost all pharmaceuticals, agrochemicals, food additives and materials. The invention of methods for the formation of bonds between C and N atoms is of strategic importance for the discovery and evolution of molecules with direct implications on the quality of our lives. Despite this fundamental relevance, forming C–N bonds is still a very challenging task.
This proposal aims to deliver transformative advances for the development of new efficient and selective strategies for the synthesis of N-containing molecules by harnessing visible-light as inexpensive and sustainable source of energy.
I aim to challenge preconceptions about the field of organic chemistry and to develop innovative methods to control, modulate and transform the reactivity of nitrogen-centered radicals (NCRs), an entire class of reactive intermediates for which there are only limited applications in modern organic chemistry.
My research group has developed two novel visible-light-mediated ways of generating NCRs, and I aim to: (1) Harness and explore the unique features of visible-light-mediated transformations to provide novel multicomponent reactions of NCRs. (2) Establish NCRs as viable partners in asymmetric photoredox catalysis and use them for the easy construction of complex molecules with defined 3D shapes. (3) Merge the visible-light generation of NCRs with organocatalysis to enable novel dual catalytic asymmetric protocols. (4) Combine the NCRs with transition metal catalysis and discover unprecedented transformations that go beyond photoredox catalysis and transition metal catalysis alone.
This cohesive and innovative approach will develop new tools essential for the assembly of complex molecules with biological, therapeutic and agrochemical properties. Overall this project will transform the way C–N bonds are forged and how N-containing molecules are assembled. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1126/science.aar8048 | Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation | The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1371/journal.pcbi.1003736 | Structure-Function Discrepancy: Inhomogeneity and Delays in Synchronized Neural Networks | The discrepancy between structural and functional connectivity in neural systems forms the challenge in understanding general brain functioning. To pinpoint a mapping between structure and function, we investigated the effects of (in)homogeneity in coupling structure and delays on synchronization behavior in networks of oscillatory neural masses by deriving the phase dynamics of these generic networks. For homogeneous delays, the structural coupling matrix is largely preserved in the coupling between phases, resulting in clustered stationary phase distributions. Accordingly, we found only a small number of synchronized groups in the network. Distributed delays, by contrast, introduce inhomogeneity in the phase coupling so that clustered stationary phase distributions no longer exist. The effect of distributed delays mimicked that of structural inhomogeneity. Hence, we argue that phase (de-)synchronization patterns caused by inhomogeneous coupling cannot be distinguished from those caused by distributed delays, at least not by the naked eye. The here-derived analytical expression for the effective coupling between phases as a function of structural coupling constitutes a direct relationship between structural and functional connectivity. Structural connectivity constrains synchronizability that may be modified by the delay distribution. This explains why structural and functional connectivity bear much resemblance albeit not a one-to-one correspondence. We illustrate this in the context of resting-state activity, using the anatomical connectivity structure reported by Hagmann and others. | [
"Neuroscience and Disorders of the Nervous System",
"Mathematics"
]
|
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