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10.18632/oncotarget.19567
The AF4-MLL fusion transiently augments multilineage hematopoietic engraftment but is not sufficient to initiate leukemia in cord blood CD34<sup>+</sup> cells
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs). Therefore, AF4-MLL might represent a key genetic lesion contributing to t(4;11)-driven leukemogenesis. Here, we aimed to establish a humanized mouse model by using AF4-MLL to analyze its transformation potential in human cord blood-derived CD34+ HSPCs. We show that AF4-MLL-expressing human CD34+ HSPCs provide enhanced long-term hematopoietic reconstitution in primary immunodeficient recipients but are not endowed with subsequent self-renewal ability upon serial transplantation. Importantly, expression of AF4-MLL in primary neonatal CD34+ HSPCs failed to render any phenotypic or hematological sign of disease, and was therefore not sufficient to initiate leukemia within a 36-week follow-up. Species-specific (epi)-genetic intrinsic determinants may underlie the different outcome observed when AF4-MLL is expressed in murine or human HSPCs.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
W2066478212
Limits of hybrid political orders: the case of Somaliland
Abstract Hybrid political orders are in the literature discussed as a heuristic tool to understand how power and legitimacy are negotiated in settings where the Western model of the liberal democratic state does not work. Sometimes they are presented as an alternative model for successful statehood, e.g., by combining ‘traditional’ and ‘modern’ political institutions. The Republic of Somaliland is frequently presented as functioning hybrid political order. A cornerstone for Somaliland's success was the integration of traditional authorities in government. These authorities engaged in peace-building and state formation in the early 1990s. Their role was institutionalized in the ‘House of Elders’, the upper house of parliament. This article argues that the hybrid political order of Somaliland has outlived its success. What is left at the beginning of the 21st century is an imbalanced and in many regards ‘crippled’ hybrid. It threatens democratic progress and undermines the authority and legitimacy of the st...
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions" ]
US 2021/0062204 W
DETOXIFICATION DEVICE HAVING HEATED FILTER FOR KILLING PATHOGENS
A detoxification device for removing pathogens from air within an environment. The detoxification device may include a filtration media for catching and retaining particles larger than about 0.3 micrometers (pm) with an efficiency of at least 99%, The detoxification device may also include a heating element having a metallic foam. The heating element may be heated upon application of an electrical current to the heating element. The heating element may, upon being heated, heat the filtration media to a target temperature that is effective to kill a pathogen.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1039/C7CC04289B
Scavenger Templates A Systems Chemistry Approach To The Synthesis Of Porphyrin Based Molecular Wires
A hexa-pyridyl template can be used as a scavenger to facilitate the synthesis of a linear porphyrin dodecamer from a mixture of linear hexamers with one or two terminal reactive groups. The template suppresses polymer formation by rapidly cyclizing the fully deprotected hexamer, thus up-regulating formation of the linear dodecamer.
[ "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
10.1111/ajps.12225
Are Voters Equal under Proportional Representation?
We develop and apply a new conceptual framework and measure for evaluating electoral systems, focusing on (in)equality in parliamentary representation. Our main arena of interest is proportional representation with districts, an electoral system employed by more than half of democratic states, and we draw on an almost entirely overlooked fact: Electoral regimes vary substantially within countries, with some voters casting their ballot in semi-majoritarian districts of few representatives and others in large and proportional ones. This within-country institutional variation, we contend, affects representational (in)equality. Evaluating equality in parliamentary representation, we demonstrate that districted proportional representation often leads to overrepresentation of voters supporting right-leaning parties. Utilizing district-level data from 20 Western parliamentary democracies and complementing our within-country approach with a cross-country analysis, we further show that where parliaments are elected by large and small districts, representational inequality among voters is greater compared with countries in which parliament is elected by even-magnitude districts.
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions" ]
950262
DEAD-box ATPases as master regulators of phase-separated compartments to control cellular RNA flux and the remodeling of RNA-protein complexes
Life ultimately depends on the tight control of gene expression, which requires an ordered and efficient processing of various RNA molecules. Messenger RNAs (mRNAs) – bound by a constantly changing coat of passenger proteins - transit from transcription in the nucleus to translation and ultimately decay in the cytoplasm. Similarly, ribosomal rRNAs migrate through the nucleolus where they gradually en-counter ribosomal proteins to assemble functional ribosomes. Still, we know very little about the pro-cesses that orchestrate this flux of RNA in a temporal and spatial manner. Intriguingly, many RNA processing steps occur in membraneless organelles formed by liquid-liquid phase separation, e.g. nuclear speckles or the nucleolus, but the function of condensate formation in RNA processing is not known. I have discovered that the family of DEAD-box ATPases (DDXs) are master regulators of RNA-containing membraneless organelles, from bacteria to man. DDXs use their low-complexity domains and ATPase activity to regulate condensate dynamics and RNA flux through these compartments. I propose that cells use DDX-controlled condensate ‘stations’ to establish an RNA ‘transit map’ to reg-ulate the cellular flux of mRNA and rRNA molecules and to spatially and temporally control RNA pro-cessing. In three work packages, I will (1) characterize central DDXs that control mRNA flux and use DDX mutants as unique tools to map passenger protein changes along the life of an mRNA; (2) charac-terize how DDXs regulate the formation of the phase-separated nucleolar environment and facilitate the flux of rRNA during ribosome assembly; (3) dissect how DDX condensates function as biomolecular filters to selectively enrich or exclude proteins, and how selectivity contributes to the remodeling of the RNA protein coat and directional RNA flux. Our research will provide key novel insight into our understanding of RNA processing and uncover novel layers of gene expression regulation.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.3389/fimmu.2019.01462
The metabolic signature of macrophage responses
Macrophages are a heterogeneous population of immune cells playing several and diverse functions in homeostatic and immune responses. The broad spectrum of macrophage functions depends on both heterogeneity and plasticity of these cells, which are highly specialized in sensing the microenvironment and modify their properties accordingly. Although it is clear that macrophage phenotypes are difficult to categorize and should be seen as plastic and adaptable, they can be simplified into two extremes: A pro-inflammatory (M1) and an anti-inflammatory/pro-resolving (M2) profile. Based on this definition, M1 macrophages are able to start and sustain inflammatory responses, secreting pro-inflammatory cytokines, activating endothelial cells, and inducing the recruitment of other immune cells into the inflamed tissue; on the other hand, M2 macrophages promote the resolution of inflammation, phagocytose apoptotic cells, drive collagen deposition, coordinate tissue integrity, and release anti-inflammatory mediators. Dramatic switches in cell metabolism accompany these phenotypic and functional changes of macrophages. In particular, M1 macrophages rely mainly on glycolysis and present two breaks on the TCA cycle that result in accumulation of itaconate (a microbicide compound) and succinate. Excess of succinate leads to Hypoxia Inducible Factor 1α (HIF1α) stabilization that, in turn, activates the transcription of glycolytic genes, thus sustaining the glycolytic metabolism of M1 macrophages. On the contrary, M2 cells are more dependent on oxidative phosphorylation (OXPHOS), their TCA cycle is intact and provides the substrates for the complexes of the electron transport chain (ETC). Moreover, pro- A nd anti-inflammatory macrophages are characterized by specific pathways that regulate the metabolism of lipids and amino acids and affect their responses. All these metabolic adaptations are functional to support macrophage activities as well as to sustain their polarization in specific contexts. The aim of this review is to discuss recent findings linking macrophage functions and metabolism.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1007/s10670-019-00128-z
The Logic of Fast and Slow Thinking
AbstractWe present a framework for epistemic logic, modeling the logical aspects of System 1 (“fast”) and System 2 (“slow”) cognitive processes, as per dual process theories of reasoning. The framework combines non-normal worlds semantics with the techniques of Dynamic Epistemic Logic. It models non-logically-omniscient, but moderately rational agents: their System 1 makes fast sense of incoming information by integrating it on the basis of their background knowledge and beliefs. Their System 2 allows them to slowly, step-wise unpack some of the logical consequences of such knowledge and beliefs, by paying a cognitive cost . The framework is applied to three instances of limited rationality, widely discussed in cognitive psychology: Stereotypical Thinking, the Framing Effect, and the Anchoring Effect.
[ "The Human Mind and Its Complexity", "Computer Science and Informatics" ]
10.1080/15476286.2016.1142039
Bidirectional Coupling Of Splicing And Atm Signaling In Response To Transcription Blocking Dna Damage
In response to DNA damage cells activate intricate protein networks to ensure genomic fidelity and tissue homeostasis. DNA damage response signaling pathways coordinate these networks and determine cellular fates, in part, by modulating RNA metabolism. Here we discuss a replication-independent pathway activated by transcription-blocking DNA lesions, which utilizes the ATM signaling kinase to regulate spliceosome function in a reciprocal manner. We present a model according to which, displacement of co-transcriptional spliceosomes from lesion-arrested RNA polymerases, culminates in R-loop formation and non-canonical ATM activation. ATM signals in a feed-forward fashion to further impede spliceosome organization and regulates UV-induced gene expression and alternative splicing genome-wide. This reciprocal coupling between ATM and the spliceosome highlights the importance of ATM signaling in the cellular response to transcription-blocking lesions and supports a key role of the splicing machinery in this process.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1088/1748-9326/ab8589
Quantifying the potential for climate change mitigation of consumption options
Background. Around two-thirds of global GHG emissions are directly and indirectly linked to household consumption, with a global average of about 6 tCO2eq/cap. The average per capita carbon footprint of North America and Europe amount to 13. 4 and 7. 5 tCO2eq/cap, respectively, while that of Africa and the Middle East - to 1. 7 tCO2eq/cap on average. Changes in consumption patterns to low-carbon alternatives therefore present a great and urgently required potential for emission reductions. In this paper, we synthesize emission mitigation potentials across the consumption domains of food, housing, transport and other consumption. Methods. We systematically screened 6990 records in the Web of Science Core Collections and Scopus. Searches were restricted to (1) reviews of lifecycle assessment studies and (2) multiregional input-output studies of household consumption, published after 2011 in English. We selected against pre-determined eligibility criteria and quantitatively synthesized findings from 53 studies in a meta-review. We identified 771 original options, which we summarized and presented in 61 consumption options with a positive mitigation potential. We used a fixed-effects model to explore the role of contextual factors (geographical, technical and socio-demographic factors) for the outcome variable (mitigation potential per capita) within consumption options. Results and discussion. We establish consumption options with a high mitigation potential measured in tons of CO2eq/capita/yr. For transport, the options with the highest mitigation potential include living car-free, shifting to a battery electric vehicle, and reducing flying by a long return flight with a median reduction potential of more than 1. 7 tCO2eq/cap. In the context of food, the highest carbon savings come from dietary changes, particularly an adoption of vegan diet with an average and median mitigation potential of 0. 9 and 0. 8 tCO2eq/cap, respectively. Shifting to renewable electricity and refurbishment and renovation are the options with the highest mitigation potential in the housing domain, with medians at 1. 6 and 0. 9 tCO2eq/cap, respectively. We find that the top ten consumption options together yield an average mitigation potential of 9. 2 tCO2eq/cap, indicating substantial contributions towards achieving the 1. 5 C-2 C target, particularly in high-income context.
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
10.1109/SEAA.2012.11
Engineering Emergent Semantics Into Pervasive Resource Discovery
Pervasive environments are composed as spontaneous aggregation of heterogeneous and independent devices, which may seamlessly consume, but also provide, software resources over the network. As result, applications emerge from the dynamic composition of the resources available within the environment. This requires applications of being semantic-aware, to reason about and learn from the environment. However, due to the inherent high degree of dynamism characterizing pervasive environments, semantics cannot be established a-priori, rather it should "emerge" from online negotiations among involved parties. This paper, formalizes emergent semantics principles into formal foundations, and shows, as proof of concept, how to engineer such foundations into a fully distributed semantic service discovery.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
W1997148938
Hybrid general-purpose computation on GPU (GPGPU) and computer graphics synthetic aperture radar simulation for complex scenes
In this paper, a new hybrid general-purpose computation on GPU (GPGPU) and computer graphics synthetic aperture radar (SAR) simulation method for complex scenes is proposed. Previous SAR simulations for complex scenes only use GPU’s graphics capabilities for scattering calculation in graphical electromagnetic computing (GRECO) algorithm. The new hybrid method use GPU’s graphics and parallel computing capabilities for geometry modeling, scattering map and raw data calculation in SAR simulation of complex scenes. The advantages of the new method rely on the three contributions: GPU hardware provides lots of stream processors for threads calculating, common unified device architecture (CUDA) environment runs thousands of threads working in parallel for assigned task, raw data simulation adopts the fine-grained task parallelism. Compared with classical algorithms, the method not only ensures the accuracy of scattering calculation with GRECO algorithm, but also improves the computational efficiency greatlyfor complex scenes consideration. The results show that the method is able to obtain the speedup about 30 times on entry-level GPU.   Key words: Synthetic aperture radar (SAR), raw data simulation, parallel processing, general-purpose computation on GPU (GPGPU), computer graphics.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1002/anie.201603562
Structural Analysis using SHALiPE to Reveal RNA G-Quadruplex Formation in Human Precursor MicroRNA
RNA G-quadruplex (rG4) structures are of fundamental importance to biology. A novel approach is introduced to detect and structurally map rG4s at single-nucleotide resolution in RNAs. The approach, denoted SHALiPE, couples selective 2′-hydroxyl acylation with lithium ion-based primer extension, and identifies characteristic structural fingerprints for rG4 mapping. We apply SHALiPE to interrogate the human precursor microRNA 149, and reveal the formation of an rG4 structure in this non-coding RNA. Additional analyses support the SHALiPE results and uncover that this rG4 has a parallel topology, is thermally stable, and is conserved in mammals. An in vitro Dicer assay shows that this rG4 inhibits Dicer processing, supporting the potential role of rG4 structures in microRNA maturation and post-transcriptional regulation of mRNAs.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Physical and Analytical Chemical Sciences" ]
10.1016/j.annepidem.2013.05.014
Time away from work predicts later cognitive function: Differences by activity during leave
Purpose: We sought to examine how different activities performed during employment gaps are associated with later cognitive function and change. Methods: Five cognitive measures were used to indicate cognitive impairment of 18,259 respondents to the Survey of Health, Ageing, and Retirement in Europe (ages 50-73) in 2004/5 or 2006/7. Using complete employment histories, employment gaps of ≥6 months between ages 25 and 65 were identified. Results: Controlling for early life socioeconomic status, school performance, and education, higher risk of cognitive impairment was associated with employment gaps described as unemployment (odds ratio [OR],1. 18; 95% confidence interval [CI], 1. 04-1. 35) and sickness (OR,1. 78; 95% CI, 1. 52-2. 09). In contrast, lower risk of cognitive impairment was associated with employment gaps described as training (OR,0. 73; 95% CI, 0. 52-1. 01) or maternity leave (OR,0. 65; 95% CI, 0. 57-0. 79). In longitudinal mixed effects models, training and maternity leave were associated with lower 2-year aging-related cognitive decline. Discussion: Periods away from work described as unemployment or sickness are associated with lower cognitive function, whereas maternity and training leaves are associated with better late-life cognitive function. Both causation and selection mechanisms may explain these findings.
[ "The Human Mind and Its Complexity", "The Social World and Its Interactions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W2149278034
Evaluation of Sustainability of Smallholder Dairy Production Systems in the Highlands of Mexico During the Rainy Season
A sustainability evaluation was undertaken with 22 smallholder dairy farms in the highlands of Mexico; following the IDEA method in the agroecological, socioterritorial, and economic scales (all scales are out of 100). Sustainability was highest for the agroecological scale (59/100), intermediate for the socioterritorial scale (53/100), and lowest on the economic scale (43/100). The sustainability of a farm is the lowest score of the three scales. In most farms, the lowest was the economic scale. A cluster analysis led to the identification of five distinct groups: Cluster 1 defined two farms not related to others, cluster 2 farms (4) were those with high agroecological scores, cluster 3 farms (8) were most representative of the area, cluster 4 included two farms with low socioterritorial and economic sustainability scores, and cluster 5 was made up of the remaining six farms with the highest economic sustainability score, but limited by the agroecological and socioterritorial scales. In all farms, there ...
[ "Earth System Science", "Human Mobility, Environment, and Space", "Individuals, Markets and Organisations" ]
10.1007/s11229-016-1202-1
On the supposed connection between proper names and singular thought
A thesis I call the name-based singular thought thesis (NBT thesis) is part of orthodoxy in contemporary philosophy of mind and language: it holds that taking part in communication involving a proper name puts one in a position to entertain singular thoughts about the name’s referent. I argue, first, that proponents of the NBT thesis have failed to explain the phenomenon of name-based singular thoughts, leaving it mysterious how name-use enables singular thoughts. Second, by outlining the reasoning that makes the NBT thesis seem compelling and showing how it can be resisted, I argue that giving up the NBT thesis is not (as is usually assumed) a cost, but rather a benefit. I do this by providing an expanded conception of understanding for communication involving names, which sheds light on the nature of communication involving names and the structure of name-using practices.
[ "Texts and Concepts", "The Human Mind and Its Complexity" ]
883275
A diagnostic tool for endometritis in cows, based on a portable automated image recognition software
Endometritis is a curable uterine infection that is highly prevalent in cow farms affecting approximately 30% of cows per year, with up to 70% incidence in some herds. A farm with just 1,500 cows and with a typical incidence rate of 30% has a loss of up to €146,000 a year due to the costs associated with endometritis. Current solutions are slow, expensive, require specialized personnel and have low reliability (53%). Oculyze offers Better Dairy, an automated image recognition tool leveraging a proprietary smart algorithm using a smartphone-based microscope and a sampling kit for the diagnosis of subclinical endometritis in cows. The diagnostic tool can be easily used by anyone without professional training. It does not require expensive equipment or lab testing, just a regular smartphone. Better Dairy makes laboratory testing an easy and affordable task. During the feasibility assessment, a minimum viable product will be defined, a go-to-market strategy and a supply chain will be established, as well as further development plan will be drafted. Within the overall project, Oculyze seeks to finalize the design of the Better Dairy, upgrade the recognition software, transfer the production line to a CMO and validate the performance through pilot with 2 cattle farms.
[ "Products and Processes Engineering", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1111/cobi.12462
Quantifying the erosion of natural darkness in the global protected area system
The nighttime light environment of much of the earth has been transformed by the introduction of electric lighting. This impact continues to spread with growth in the human population and extent of urbanization. This has profound consequences for organismal physiology and behavior and affects abundances and distributions of species, community structure, and likely ecosystem functions and processes. Protected areas play key roles in buffering biodiversity from a wide range of anthropogenic pressures. We used a calibration of a global satellite data set of nighttime lights to determine how well they are fulfilling this role with regard to artificial nighttime lighting. Globally, areas that are protected tend to be darker at night than those that are not, and, with the exception of Europe, recent regional declines in the proportion of the area that is protected and remains dark have been small. However, much of these effects result from the major contribution to overall protected area coverage by the small proportion of individual protected areas that are very large. Thus, in Europe and North America high proportions of individual protected areas (>17%) have exhibited high levels of nighttime lighting in all recent years, and in several regions (Europe, Asia, South and Central America) high proportions of protected areas (32-42%) have had recent significant increases in nighttime lighting. Limiting and reversing the erosion of nighttime darkness in protected areas will require routine consideration of nighttime conditions when designating and establishing new protected areas; establishment of appropriate buffer zones around protected areas where lighting is prohibited; and landscape level reductions in artificial nighttime lighting, which is being called for in general to reduce energy use and economic costs.
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
10.1016/j.bbamcr.2008.05.013
Prohibitin function within mitochondria: Essential roles for cell proliferation and cristae morphogenesis
Prohibitins comprise an evolutionary conserved and ubiquitously expressed family of membrane proteins. Various roles in different cellular compartments have been proposed for prohibitin proteins. Recent experiments, however, identify large assemblies of two homologous prohibitin subunits, PHB1 and PHB2, in the inner membrane of mitochondria as the physiologically active structure. Mitochondrial prohibitin complexes control cell proliferation, cristae morphogenesis and the functional integrity of mitochondria. The processing of the dynamin-like GTPase OPA1, a core component of the mitochondrial fusion machinery, has been defined as a key process affected by prohibitins. The molecular mechanism of prohibitin function, however, remained elusive. The ring-like assembly of prohibitins and their sequence similarity with lipid raft-associated SPFH-family members suggests a scaffolding function of prohibitins, which may lead to functional compartmentalization in the inner membrane of mitochondria.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W1631012431
Fair Trade and justice: a comment on Walton and Deneulin
In this article we first point out that the different conceptualisations of Fair Trade, which are sometimes analytically contradictory, actually form a coordinated set. Understanding the Fair Trade project is impossible without taking these interlinked conceptualisations into consideration. Second, this set basically forms a mechanism of structural, institutional and moral reforms that guide actions. In this way Fair Trade sets out to produce less injustice than is usually the case with the structures and institutions that govern conventional trade. Nevertheless, it does not try to define what a just society is or even to perfectly define ‘fair trade’. This implies the adoption of a comparative justice angle. It is precisely by linking comparative individual situations with the structures that produce these situations that relative justice can find its strength and purpose.
[ "Texts and Concepts", "Institutions, Governance and Legal Systems", "The Social World and Its Interactions" ]
171358
Inorganic therapeutic nanoparticles for osteoporosis
The aim of the proposed interdisciplinary project is to design, make and test novel nanoparticles that will have direct and rapid impact in osteoporosis. The unique aspect of these injectable nanoparticles is that they will deliver active therapy locally, to where it is needed, and that the cargo is not a conventional drug, but a sustained delivery of a combination of active inorganic cations and rare earth nanoparticles. Certain cations can promote bone growth and inhibit resorption and nanoceria can scavenge free radicals that would otherwise accelerate osteoporosis. Systemic concentrations of active agents will be much smaller that caused by taking oral drugs. Delivery will be sustained because it is controlled by the dissolution rate of biodegradable mesoporous silica nanoparticles, which will improve over biodegradable polymer capsules that often deliver a burst release of their drug cargo. Beyond the project, long-term impact could include slowing metastasis of tumours into bone (e.g. breast cancer to the sternum). The biodegradable mesoporous silica nanoparticles will be synthesised by sol-gel, while the nanoceria will be synthesized by co-precipitation method and microwave treatment and entrapped within the silica network. Key aspects will be: incorporation of active ions and nanoceria within monodispersed silica nanoparticles of controlled size; ensuring the particles remain dispersed in body fluid (control of surface chemistry); testing efficacy in cell co-culture (uptake and cell stimulation) and investigating the effect of the presence of the particles on immune cells. The effect of process variables on composition, particle size, bioactivity, degradation rate, radical scavenger ability and the cellular response will be investigated.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases", "Materials Engineering" ]
W2466691842
Molybdenum-99-producing 37-element fuel bundle neutronically and thermal-hydraulically equivalent to a standard CANDU fuel bundle
Abstract 99m Tc, the most commonly used radioisotope in diagnostic nuclear medicine, results from the radioactive decay of 99 Mo which is currently being produced at various research reactors around the globe. In this study, the potential use of CANDU power reactors for the production of 99 Mo is investigated. A modified 37-element fuel bundle, suitable for the production of 99 Mo in existing CANDU-type reactors is proposed. The new bundle is specifically designed to be neutronically and thermal-hydraulically equivalent to the standard 37-element CANDU fuel bundle in normal, steady-state operation and, at the same time, be able to produce significant quantities of 99 Mo when irradiated in a CANDU reactor. The proposed bundle design uses fuel pins consisting of a depleted-uranium centre surrounded by a thin layer of low-enriched uranium. The new molybdenum-producing bundle is analyzed using the lattice transport code DRAGON and the diffusion code DONJON. The proposed design is shown to produce 4081 six-day Curies of 99 Mo activity per bundle when irradiated in the peak-power channel of a CANDU core, while maintaining the necessary reactivity and power rating limits. The calculated 99 Mo yield corresponds to approximately one third of the world weekly demand. A production rate of ∼3 bundles per week can meet the global demand of 99 Mo.
[ "Products and Processes Engineering", "Fundamental Constituents of Matter", "Materials Engineering" ]
W2598552155
Modelling of Consequences of Biogas Leakage from Gasholder
This paper describes modelling of consequences of biogas leakage from a gasholder on agricultural biogas station. Four scenarios were selected for the purpose of this work. A rupture of gasholders membrane and instantaneous explosion of gas cloud, blast of gas with delay, emptying of whole volume of gas (without initiation) and initiation of gas with Jet-Fire. Leakage of gas is modelled by special software and consequences are determined on the basis of results. The first scenario was modelled with help of equations because used software does not include an appropriate model. A farm with high building density was chosen as a model case. Biogas is replaced by methane because used software does not support modelling of dispersion of mixtures. From this viewpoint, a conservative approach is applied because biogas contains “only” approximately 60% of methane (in dependence on technology and processed material).
[ "Products and Processes Engineering", "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering" ]
3732344
Micro-Scale dependent, time- and space-evolving rheologies: the key for generating strain localization in the earth
RhEoVOLUTION proposes a ""revolution"" in how we define rheology (the equations relating forces to deformation) in geodynamical models. It aims at predicting the onset and evolution of strain localization. Modeling spontaneous ductile strain localization has been impossible so far, because it depends on processes active at the mm scale, which cannot be explicitly simulated in geodynamical models. The tools we designed and propose to develop in RhEoVOLUTION will make it possible. We will bridge scales and model how heterogeneity and anisotropy in the mechanical behavior of rocks control strain localization from the cm to the tens of km scale in the Earth. To do so, we will: 1. describe the heterogeneity of mechanical behavior of rocks deforming by dislocation creep by stochastic parameterizations of the rheology; 2. constrain these parameterizations by experiments with in-situ follow-up of the strain evolution and mesoscale models; 3. accelerate the calculation of the evolution of anisotropy during deformation by using supervised machine-learning; 4. quantify feedbacks between the main processes producing strain localization by comparing the predictions of models parameterized to simulate these processes to observations in natural shear zones. RhEoVOLUTION will empower the geodynamics community with a predictive tool for strain localization. It will provide explanations for localized deformation in intraplate domains and predictions of the evolution of shear zones in extensional and convergent plate margins, enhancing our understanding of the architecture of passive margins and mountain belts. We postulate it will allow modeling the most evident expression of strain localization on Earth: Plate Tectonics, that is still a challenge >50 years after the scientific revolution that established this paradigm. The tools developed in RhEoVOLUTION will also allow predicting ductile strain localization in ice and metals with possible applications in glaciology and metallurgy.
[ "Earth System Science", "Condensed Matter Physics", "Computer Science and Informatics" ]
291156
Flow Machines: Interacting with Style
Content creation is a fundamental activity for developing identities in modern individuals. Yet creativity is hardly addressed by computer science. This project addresses the issue of content creation from the perspective of Flow machines. Flow machines are interactive systems that learn how to generate content, text or music, in the user’s style. Thanks to controlled generation mechanisms, the user can then steer the machine to generate content that fits with their intentions. Flow interactions induce a multiplicative effect that boosts creativity and prompts the user to reflect on their own style. This vision stems from the success stories of several computer-assisted musical systems that showed how interactive dialogs with self-learning interactions provoke flow states. To enables full control of stylistic generation, the scientific challenge is the reification of style as a flexible texture. This challenge will be addressed by pursuing three original directions in the fields of statistical learning and combinatorial optimization: 1) the formulation of Markov-based generation as a constraint problem, 2) the development of feature generation techniques for feeding machine learning algorithms and 3) the development of techniques to transform descriptors into controllers. Two large-scale studies will be conducted with well-known creators using these Flow machines, during which the whole creation process will be recorded, stored, and analyzed, providing the first complete chronicles of professional-level artifacts. The artifacts, a music album and a novel, will be published in their respective ecosystems, and the reaction of the audience will be measured and analyzed to further assess the impact of Flow machines on creation. The technologies developed and the pilot studies will serve as pioneering experiments to turn Flow machines into a field of study and explore other domains of creation.
[ "Computer Science and Informatics", "The Human Mind and Its Complexity" ]
10.1042/bj20102090
Substrate diffusion and oxidation in GMC oxidoreductases: an experimental and computational study on fungal aryl-alcohol oxidase
AAO (aryl-alcohol oxidase) provides H2O2 in fungal degradation of lignin, a process of high biotechnological interest. The crystal structure of AAO does not show open access to the active site, where different aromatic alcohols are oxidized. In the present study we investigated substrate diffusion and oxidation in AAO compared with the structurally related CHO (choline oxidase). Cavity finder and ligand diffusion simulations indicate the substrate-entrance channel, requiring side-chain displacements and involving a stacking interaction with Tyr92. Mixed QM (quantum mechanics)/MM (molecular mechanics) studies combined with site-directed mutagenesis showed two active-site catalytic histidine residues, whose substitution strongly decreased both catalytic and transient-state reduction constants for p-anisyl alcohol in the H502A (over 1800-fold) and H546A (over 35-fold) variants. Combination of QM/MM energy profiles, protonation predictors, molecular dynamics, mutagenesis and pH profiles provide a robust answer regarding the nature of the catalytic base. The histidine residue in front of the FAD ring, AAO His502 (and CHO His466), acts as a base. For the two substrates assayed, it was shown that proton transfer preceded hydride transfer, although both processes are highly coupled. No stable intermediate was observed in the energy profiles, in contrast with that observed for CHO. QM/MM, together with solvent KIE (kinetic isotope effect) results, suggest a non-synchronous concerted mechanism for alcohol oxidation by AAO.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1073/pnas.1421056111
Place cells in the hippocampus: Eleven maps for eleven rooms
The contribution of hippocampal circuits to high-capacity episodic memory is often attributed to the large number of orthogonal activity patterns that may be stored in these networks. Evidence for high-capacity storage in the hippocampus is missing, however. When animals are tested in pairs of environments, different combinations of place cells are recruited, consistent with the notion of independent representations. However, the extent to which representations remain independent across larger numbers of environments has not been determined. To investigate whether spatial firing patterns recur when animals are exposed to multiple environments, we tested rats in 11 recording boxes, each in a different room, allowing for 55 comparisons of place maps in each animal. In each environment, activity was recorded from neuronal ensembles in hippocampal area CA3, with an average of 30 active cells per animal. Representations were highly correlated between repeated tests in the same room but remained orthogonal across all combinations of different rooms, with minimal overlap in the active cell samples from each environment. A low proportion of cells had activity in many rooms but the firing locations of these cells were completely uncorrelated. Taken together, the results suggest that the number of independent spatial representations stored in hippocampal area CA3 is large, with minimal recurrence of spatial firing patterns across environments.
[ "Neuroscience and Disorders of the Nervous System" ]
10.1016/j.yexcr.2014.07.013
Sirtuin 6 protects the heart from hypoxic damage
Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.15252/emmm.201708076
An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors
Epidermal growth factor receptor (EGFR) mutations identify patients with lung cancer who derive benefit from kinase inhibitors. However, most patients eventually develop resistance, primarily due to the T790M second-site mutation. Irreversible inhibitors (e. g. , osimertinib/AZD9291) inhibit T790M-EGFR, but several mechanisms, including a third-site mutation, C797S, confer renewed resistance. We previously reported that a triple mixture of monoclonal antibodies, 3×mAbs, simultaneously targeting EGFR, HER2, and HER3, inhibits T790M-expressing tumors. We now report that 3×mAbs, including a triplet containing cetuximab and trastuzumab, inhibits C797S-expressing tumors. Unlike osimertinib, which induces apoptosis, 3×mAbs promotes degradation of the three receptors and induces cellular senescence. Consistent with distinct mechanisms, treatments combining 3×mAbs plus sub-inhibitory doses of osimertinib synergistically and persistently eliminated tumors. Thus, oligoclonal antibodies, either alone or in combination with kinase inhibitors, might preempt repeated cycles of treatment and rapid emergence of resistance.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1007/s11229-013-0275-3
Dynamics of lying
We propose a dynamic logic of lying, wherein a 'lie that φ' (where φ is a formula in the logic) is an action in the sense of dynamic modal logic, that is interpreted as a state transformer relative to the formula φ. The states that are being transformed are pointed Kripke models encoding the uncertainty of agents about their beliefs. Lies can be about factual propositions but also about modal formulas, such as the beliefs of other agents or the belief consequences of the lies of other agents. We distinguish two speaker perspectives: (Obs) an outside observer who is lying to an agent that is modelled in the system, and (Ag) an agent who is lying to another agent, and where both are modelled in the system. We distinguish three addressee perspectives: (Cred) the credulous agent who believes everything that it is told (even at the price of inconsistency), (Skep) the skeptical agent who only believes what it is told if that is consistent with its current beliefs, and (Rev) the belief revising agent who believes everything that it is told by consistently revising its current, possibly conflicting, beliefs. The logics have complete axiomatizations, which can most elegantly be shown by way of their embedding in what is known as action model logic or in the extension of that logic to belief revision.
[ "Computer Science and Informatics", "The Human Mind and Its Complexity" ]
W1600326538
Mycobacterium tuberculosis employs Cpn60.2 as an adhesin that binds CD43 on the macrophage surface
CD43 is a large sialylated glycoprotein found on the surface of haematopoietic cells and has been previously shown to be necessary for efficient macrophage binding and immunological responsiveness to Mycobacterium tuberculosis. Using capsular material from M. tuberculosis and recombinant CD43-Fc, we have employed affinity chromatography to show that Cpn60.2 (Hsp65, GroEL), and to a lesser extent DnaK (Hsp70), bind to CD43. Competitive inhibition using recombinant protein and polyclonal F(ab')(2) antibody-mediated epitope masking studies were used to evaluate M. tuberculosis binding to CD43(+/+) versus CD43(-/-) macrophages. Results showed that Cpn60.2, but not DnaK, acts as a CD43-dependent mycobacterial adhesin for macrophage binding. Assessment of the specific binding between Cpn60.2 and CD43 showed it to be saturable, with a comparatively weak affinity in the low micromolar range. We have also shown that the ability of Cpn60.2 to competitively inhibit M. tuberculosis binding to macrophages is shared by the Escherichia coli homologue, GroEL, but not by the mouse and human Hsp60 homologues. These findings add to a growing field of research that implicates molecular chaperones as having extracellular functions, including bacterial adherence to host cells. Thus, CD43 may act as a Pattern Recognition Receptor (PRR) for bacterial homologues of the 60 kDa molecular chaperone.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2013102540
Craniofacial morphology characteristics of operated unilateral complete cleft lip and palate patients in mixed dentition
The objective of this study was to analyze craniofacial morphologic characteristics at the stage of mixed dentition in Chinese children who had received surgery for unilateral complete cleft lip and palate (UCCLP) compared with the healthy population.Lateral cephalometric radiographs were taken for 2 groups of individuals: (1) 48 UCCLP patients who had been operated on before 2 years of age, and (2) 60 noncleft peers as controls.The operated UCCLP groups differed from the control group as follows: reduced cranial base length, less maxillary length, more retrognathic maxilla, retusion of the entire maxilla, more incongruous intermaxillary relation, more concave skeletal profile, and more lingually inclined maxillary and mandibular incisors.The operated UCCLP children at the mixed dentition stage showed serious craniofacial deformities and the craniofacial growth was influenced (especially in maxilla).
[ "Physiology in Health, Disease and Ageing", "Cell Biology, Development, Stem Cells and Regeneration" ]
W2022311890
Maintenance of belt conveyors using an expert system based on fuzzy logic
In recent years, conveyor belt transport systems have taken on a new significance due to numerous research studies on innovative design solutions. The application of these new developed solutions leads to considerable reduction in operational costs of transport systems, while ensuring their high reliability and service life at the same time. Nonetheless, there are still areas that pose challenge to both research and development. Typical challenges are analyzed in this paper. The solution to the problems of conveyor transport maintenance can be the implementation of a system for estimation of technical condition of conveyor belt joints. It serves as a second level safety diagnostic system for transport. Besides real-time measurements, the system enables a long-term analysis of historic data for every single joint that makes up the conveyor belt loop, from the moment of its manufacture to the final operation. The effectiveness of a conveyor belt diagnostic system primarily depends on the use of a decision supporting system. With adequate inference rules applied, this system would increase the effectiveness and shorten the time of decision-making as well as verify generated signals. The above tasks can be performed by a suitable expert system that predicts values of the analyzed time series, using the predicted values and inference rules to verify any potential false alarm signals at the same time. The idea and algorithm of such an expert system were presented in this article as well.
[ "Products and Processes Engineering", "Computer Science and Informatics" ]
10.1007/s11538-016-0194-9
Numerical Bifurcation Analysis of Physiologically Structured Populations: Consumer–Resource, Cannibalistic and Trophic Models
With the aim of applying numerical methods, we develop a formalism for physiologically structured population models in a new generality that includes consumer–resource, cannibalism and trophic models. The dynamics at the population level are formulated as a system of Volterra functional equations coupled to ODE. For this general class, we develop numerical methods to continue equilibria with respect to a parameter, detect transcritical and saddle-node bifurcations and compute curves in parameter planes along which these bifurcations occur. The methods combine curve continuation, ODE solvers and test functions. Finally, we apply the methods to the above models using existing data for Daphnia magna consuming Algae and for Perca fluviatilis feeding on Daphnia magna. In particular, we validate the methods by deriving expressions for equilibria and bifurcations with respect to which we compute errors, and by comparing the obtained curves with curves that were computed earlier with other methods. We also present new curves to show how the methods can easily be applied to derive new biological insight. Schemes of algorithms are included.
[ "Mathematics", "Environmental Biology, Ecology and Evolution" ]
10.1145/2746539.2746620
From Independence To Expansion And Back Again
We consider the following fundamental problems: Constructing k-independent hash functions with a space-time tradeoff close to Siegel's lower bound. Constructing representations of unbalanced expander graphs having small size and allowing fast computation of the neighbor function. It is not hard to show that these problems are intimately connected in the sense that a good solution to one of them leads to a good solution to the other one. In this paper we exploit this connection to present efficient, recursive constructions of k-independent hash functions (and hence expanders with a small representation). While the previously most efficient construction (Thorup, FOCS 2013) needed time quasipolynomial in Siegel's lower bound, our time bound is just a logarithmic factor from the lower bound.
[ "Computer Science and Informatics", "Mathematics" ]
W1985816518
Evaluation of the vectorial capacity of Rhipicephalus sanguineus (Acari: Ixodidae) in the transmission of canine visceral leishmaniasis
The vectorial capacity of Rhipicephalus sanguineus in the transmission of canine visceral leishmaniasis has been evaluated through a laboratory-controlled experiment. One healthy Leishmania-free dog and two dogs naturally infected with Leishmania were infested with R. sanguineus in various stages of development. Engorged larvae, unfed nymphs, engorged nymphs, unfed adults, engorged female adults and fed male adults were collected from the experimental animals and examined for Leishmania infection by optical microscopy, polymerase chain reaction (PCR) and parasite culture. Leishmania forms were not detected in any of the 433 smears prepared from engorged colonies nor in any of the 118 smears prepared from unfed colonies. However, one flagellate structure was identified in one of the smears. All pools of R. sanguineus that had fed on the infected dogs tested PCR-positive for Leishmania DNA, with the single exception of the pool of engorged larvae. In contrast, all pools of ticks that had fed on the Leishmania-free dog were PCR-negative. Leishmania growth was not observed in any of the tick colonies following incubation on culture medium. Considering that no Leishmania forms were identified in any of the meticulously analysed smears derived from engorged colonies of R. sanguineus, it appears somewhat unlikely that the maintenance and multiplication of Leishmania occurs within the tick.
[ "Immunity, Infection and Immunotherapy", "Environmental Biology, Ecology and Evolution" ]
10.1093/jxb/eru161
Reticulate evolution in Panicum (Poaceae): The origin of tetraploid broomcorn millet, P. miliaceum
Panicum miliaceum (broomcorn millet) is a tetraploid cereal, which was among the first domesticated crops, but is now a minor crop despite its high water use efficiency. The ancestors of this species have not been determined; we aimed to identify likely candidates within the genus, where phylogenies are poorly resolved. Nuclear and chloroplast DNA sequences from P. miliaceum and a range of diploid and tetraploid relatives were used to develop phylogenies of the diploid and tetraploid species. Chromosomal in situ hybridization with genomic DNA as a probe was used to characterize the genomes in the tetraploid P. miliaceum and a tetraploid accession of P. repens. In situ hybridization showed that half the chromosomes of P. miliaceum hybridized more strongly with labelled genomic DNA from P. capillare, and half with labelled DNA from P. repens. Genomic DNA probes differentiated two sets of 18 chromosomes in the tetraploid P. repens. Our phylogenetic data support the allotetraploid origin of P. miliaceum, with the maternal ancestor being P. capillare (or a close relative) and the other genome being shared with P. repens. Our P. repens accession was also an allotetraploid with two dissimilar but closely related genomes, the maternal genome being similar to P. sumatrense. Further collection of Panicum species, particularly from the Old World, is required. It is important to identify why the water-efficient P. miliaceum is now of minimal importance in agriculture, and it may be valuable to exploit the diversity in this species and its ancestors.
[ "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
643610
Neural, computational and acoustic principles of auditory sensory processing sensitivity
Hearing is an essential part of human life. We communicate through the voice, use sounds to navigate in the world and enjoy listening to music. On the other hand noise pollution in living and working environments causes serious health problems impacting millions of people and many neurological or psychiatric conditions are accompanied by sensory symptoms. The personality concept of Sensory Processing Sensitivity (SPS) describes a continuum from hyper- to hyposensitivity profiles even in the healthy population. However, the underlying neural mechanisms are unknown and an objective acoustic tool to assess auditory SPS is missing. This groundbreaking, interdisciplinary action will adress this gap by combining methods from cognitive and computational neuroscience, acoustics and psychology. I will compute mathematical models to characterize auditory performance, unravel the biological imprint of SPS using neuroimaging, and ultimately provide the scientific community with a much-needed acoustic battery to assess SPS differences objectively. Predictive coding, a general theory of neural function inspired by research in artificial intelligence, machine learning, and systems neuroscience, will provide the theoretical framework for the computational models. The interdisciplinary environment at the Center for Music in the Brain (MIB) at Aarhus University, has as its primary goal to investigate predictive coding of music. Therefore, it is the perfect location for this work and my training in psychology, auditory neurosciences and music make me the ideal person for this action. At MIB I will enhance my neuroscience (MEG), computational and programming skills. During a secondment at Oxford University I will extend the analyses to whole-brain approaches. Overall the action will foster my development as an indepent researcher capable of leading my own research group with groundbreaking potential for academia and industrial fields of application.
[ "Neuroscience and Disorders of the Nervous System", "Computer Science and Informatics", "The Human Mind and Its Complexity" ]
637853
Injectable anisotropic microgel-in-hydrogel matrices for spinal cord repair
This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration. To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed. Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
[ "Materials Engineering", "Cell Biology, Development, Stem Cells and Regeneration", "Neuroscience and Disorders of the Nervous System", "Prevention, Diagnosis and Treatment of Human Diseases" ]
268648
Next Generation Genetics of Cancer Predisposition
Unravelling genetic components of human tumor predisposition has contributed significantly to our understanding on molecular basis of cancer, and cancer prevention in the context of hereditary tumor susceptibility is one of the early examples of benefits from genetic disease information. Research into cancer susceptibility is of great importance, and as shown in this proposal Finland provides unique interdisciplinary possibilities to take the field forward. Indeed, in the near future ability to recruit very small groups of patients with a potentially novel cancer susceptibility phenotype will be more relevant than ever. Such materials have been resistant to previous gene identification approaches but lend themselves towards success by exomic and whole genome sequencing. Important discoveries are anticipated in the following fields of research to be conducted under NGG: 1) Identification of rare high-penetrance Mendelian cancer predisposition conditions, and the respective susceptibility genes. One should note that the impact of a gene discovery for basic understanding of key cellular processes is not related to the frequency of the predisposition condition (e.g. RB, LKB1, P53 etc). 2) Identification of moderate penetrance cancer susceptibility genes. Such phenotypes have been difficult to approach with traditional gene identification methods because large pedigrees with multiple affected individuals and few or no phenocopies are not easily identified. Also, the current GWAS approaches are not ideal to detect these loci due to relative rarity of the responsible variants. 3) Characterization of common variants associated with cancer susceptibility.
[ "Integrative Biology: from Genes and Genomes to Systems", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1038/nsmb.1905
The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, the human protein was purified. It was found to bind selectively to single-stranded DNA (ssDNA), and to ssDNA in tailed duplexes and replication fork structures. Monomeric and dimeric forms of BRCA2 were observed by EM. BRCA2 directed the binding of RAD51 recombinase to ssDNA, reduced the binding of RAD51 to duplex DNA and stimulated RAD51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1007/JHEP12(2018)078
Holographic Compact Stars Meet Gravitational Wave Constraints
We investigate a simple holographic model for cold and dense deconfined QCD matter consisting of three quark flavors. Varying the single free parameter of the model and utilizing a Chiral Effective Theory equation of state (EoS) for nuclear matter, we find four different compact star solutions: traditional neutron stars, strange quark stars, as well as two non-standard solutions we refer to as hybrid stars of the second and third kind (HS2 and HS3). The HS2s are composed of a nuclear matter core and a crust made of stable strange quark matter, while the HS3s have both a quark mantle and a nuclear crust on top of a nuclear matter core. For all types of stars constructed, we determine not only their mass-radius relations, but also tidal deformabilities, Love numbers, as well as moments of inertia and the mass distribution. We find that there exists a range of parameter values in our model, for which the novel hybrid stars have properties in very good agreement with all existing bounds on the stationary properties of compact stars. In particular, the tidal deformabilities of these solutions are smaller than those of ordinary neutron stars of the same mass, implying that they provide an excellent fit to the recent gravitational wave data GW170817 of LIGO and Virgo. The assumptions underlying the viability of the different star types, in particular those corresponding to absolutely stable quark matter, are finally discussed at some length.
[ "Fundamental Constituents of Matter", "Universe Sciences" ]
W2117547260
On Newton’s method and Halley’s method for the principal <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif" overflow="scroll"><mml:mrow><mml:mi>p</mml:mi></mml:mrow></mml:math>th root of a matrix
If A is a matrix with no negative real eigenvalues and all zero eigenvalues of A are semisimple, the principal p th root of A can be computed by Newton’s method or Halley’s method, with a preprocessing procedure if necessary. We prove a new convergence result for Newton’s method, and discover an interesting property of Newton’s method and Halley’s method in terms of series expansions. We explain how the convergence of Newton’s method and Halley’s method can be improved when the eigenvalues of A are known or when A is a singular matrix. We also prove new results on p th roots of M -matrices and H -matrices, and consider the application of Newton’s method and Halley’s method to find the principal p th roots of these special matrices.
[ "Mathematics" ]
10.1063/1.4945792
Energy Utilization In Fluctuating Biological Energy Converters
We have argued previously [Szoke et al. , FEBS Lett. 553, 18–20 (2003); Curr. Chem. Biol. 1, 53–57 (2007)] that energy utilization and evolution are emergent properties based on a small number of established laws of physics and chemistry. The relevant laws constitute a framework for biology on a level intermediate between quantum chemistry and cell biology. There are legitimate questions whether these concepts are valid at the mesoscopic level. Such systems fluctuate appreciably, so it is not clear what their efficiency is. Advances in fluctuation theorems allow the description of such systems on a molecular level. We attempt to clarify this topic and bridge the biochemical and physical descriptions of mesoscopic systems.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1016/j.atmosenv.2008.10.059
Deposition rates on smooth surfaces and coagulation of aerosol particles inside a test chamber
Because aerosol particle deposition is an important factor in indoor air quality, many empirical and theoretical studies have attempted to understand the process. In this study, we estimated the deposition rate of aerosol particles on smooth aluminum surfaces inside a test chamber. We investigated the influence of turbulent intensity due to ventilation and fan operation. We also investigated two important processes in particle deposition: turbophoresis, which is significant for micron particles, and coagulation, which is relevant to ultrafine particles (UFP diameter <0. 1 μm) at high particle concentrations. Our analysis included semi-empirical estimates of the deposition rates that were compared to available deposition models and verified with simulations of an aerosol dynamics model. In agreement with previous studies, this study found that induced turbulent intensity greatly enhanced deposition rates of fine particles (FP diameter <1 μm). The deposition rate of FP was proportional to the ventilation rate, and it increased monotonically with fan speed. With our setup, turbophoresis was very important for coarse particles larger than 5 μm. The coagulation of aerosol particles was insignificant when the particle concentration was less than 104 cm-3 during fan operation. The model simulation results verified that the aerosol dynamics module incorporated in our Multi-Compartment and Size-Resolved Indoor Aerosol Model (MC-SIAM) was valid. The behavior of aerosol particles inside our chamber was similar to that found in real-life conditions with the same ventilation rates (0. 018-0. 39 h-1) and similar air mixing modes. Therefore, our findings provide insight into indoor particle behavior.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
10.1002/jgrd.50828
Gas-particle partitioning of primary organic aerosol emissions: 3. Biomass burning
Atmospheric organic aerosol concentrations depend in part on the gas-particle partitioning of primary organic aerosol (POA) emissions. Consequently, heating and dilution were used to investigate the volatility of biomass-burning smoke particles from combustion of common North American trees/shrubs/grasses during the third Fire Lab at Missoula Experiment. Fifty to eighty percent of the mass of biomass-burning POA evaporated when isothermally diluted from plume- (~1000 μg m-3) to ambient-like concentrations (~10 μg m-3), while roughly 80% of the POA evaporated upon heating to 100°C in a thermodenuder with a residence time of ~14 sec. Therefore, the majority of the POA emissions were semivolatile. Thermodenuder measurements performed at three different residence times indicated that there were not substantial mass transfer limitations to evaporation (i. e. , the mass accommodation coefficient appears to be between 0. 1 and 1). An evaporation kinetics model was used to derive volatility distributions and enthalpies of vaporization from the thermodenuder data. A single volatility distribution can be used to represent the measured gas-particle partitioning from the entire set of experiments, including different fuels, organic aerosol concentrations, and thermodenuder residence times. This distribution, derived from the thermodenuder measurements, also predicts the dilution-driven changes in gas-particle partitioning. This volatility distribution and associated emission factors for each fuel studied can be used to update emission inventories and to simulate the gas-particle partitioning of biomass-burning POA emissions in chemical transport models. American Geophysical Union. All Rights Reserved.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
169593
European holocaust research infrastructure
The European Holocaust Research Infrastructure (EHRI) project seeks to transform archival research on the Holocaust. The vision of EHRI is to integrate the data, services and expertise of existing Holocaust infrastructures on an unprecedented scale. It will allow researchers from across the globe transnational and virtual access to the integrated infrastructure, and provide them with innovative digital tools and methods to (collaboratively) explore and analyse Holocaust sources. EHRI will thereby become an indispensable tool for the study of the Holocaust from a pan-European perspective. EHRI is based on an advanced community that has already achieved a significant co-ordination of its efforts, not least thanks to the activities undertaken during EHRI's first phase. The aim of the second phase is to further expand this community. The EHRI consortium includes 22 partners, spread across Europe and beyond. This consortium, as well as a network of regional contact points, enables EHRI to reach those regions where much valuable Holocaust source material is located, but where access has hitherto been problematic, especially in South-Eastern and Eastern Europe. EHRI includes measures to build capacity in such regions, thereby ensuring that institutions and people across Europe can contribute to, and make use of, the EHRI infrastructure. EHRI will continue to serve as a 'best practice' model for other humanities projects, and its innovative approach to data integration, management and retrieval will have impact in the wider cultural and IT industries. Although EHRI is geared towards scholarly communities, open online availability of reliable Holocaust material is important for the larger public, as the Holocaust is deeply rooted in the development of European societies. European support for the study of this most traumatic historical event is essential to achieve a comprehensive approach to the history of the Holocaust as a shared European phenomenon.
[ "The Study of the Human Past", "Computer Science and Informatics" ]
865724
NanophononIcs for QUantum information procEssing
Over the past thirty years, the remarkable technological advances in microfabrication processes have thrust mechanical vibrations into the quantum realm. The intrinsic coherence of mechanical motion and the capability to couple it to other physical degrees of freedom hold promises of scalable hybrid quantum platforms. But mechanical vibrations are also powerful conveyors of physical information. They are ubiquitously used in wireless communication systems, where bulk and surface acoustic wave (BAW and SAW) devices are prevalent. Their high achievable quality factors and frequencies, as well as their low propagation speed, are appropriate ingredients for information processing: they are synonymous of storage and delay. Recent works have shown that SAW could be operated in the single-phonon regime, potentially behaving as a quantum bus between solid-state qubits. The proposed approaches, however, do not yet take advantage of wave propagation management at the substrate surface itself. The uNIQUE project aims at the development of an all-electro-acousto-mechanical quantum information platform exploiting the full potential offered by surface acoustic waves in the single-phonon regime, and by mechanical resonators beyond the standard quantum limit. It adopts a yet unexplored approach at the crossing of phononics, nanomechanics and quantum acoustics to yield a fully coherent mechanical playground that can be used at the interface with other solid-state or photon qubits or as an independent quantum signal processing system. It will exploit the substrate surface to prepare and transfer non-classical states of motion of surface-coupled phononic resonators with the utmost ambition to encode the state information in a travelling single-phonon, allowing remote entanglement. This platform will allow manipulating quantum states in exceedingly compact systems driven by a sheer radio-frequency signal.
[ "Condensed Matter Physics", "Fundamental Constituents of Matter", "Systems and Communication Engineering" ]
10.1002/pssr.201105247
Electronics with and on paper
Today there is a strong interest in the scientific and industrial community concerning the use of biopolymers for electronic applications, driven mainly by low-cost and disposable applications. Adding to this interest, we must recognise the importance of the dream of wireless auto-sustained and low-energy-consumption electronics. This dream can be fulfilled by cellulose paper, the lightest and the cheapest known substrate material, as well as the Earth's major biopolymer and of tremendous global economic importance. Most of the paper used up to now is optimised in terms of the required mechanical and physical properties to be used as the support of inks of different origins. In the future, specific electronic heterogeneous paper sheets should be fabricated aiming to get paper fibers with required bulk and surface functionalities, proper water/vapour barrier, size and diameter/thickness of the fibrils and full paper thickness. This will be the function of components/devices to be incorporated/integrated such as thin-film transistors, complementary metal oxide semiconductor devices, passive electronic components (resistances, inductors and capacitors), memory transistors, electrochromics and thin-film paper batteries.
[ "Systems and Communication Engineering", "Materials Engineering" ]
W4313194398
Spiel im Morgengrauen (1926/1927)
27 Jahre nach der Publikation von Lieutenant Gustl (1900) erscheint Schnitzlers zweite »Leutn[ants]novella « (Tb, 5.3.1924), Spiel im Morgengrauen, bei S. Fischer in Berlin. Der Entstehungsprozess der Novelle, die sich zugleich als Abwandlung und Aktualisierung früher Figuren und Grundmotive lesen lässt (vgl. Rey 1968, 126), erstreckt sich über einen Zeitraum von zehn Jahren, wobei die Periode 1923/26 als eigentliche Schaffens- und Bearbeitungsphase zu betrachten ist. Nach den ersten Entwürfen im Mai 1916 (vgl. Kiermeier-Debre 2011, 137) nimmt Schnitzler die Novelle im September 1923 unter dem Arbeitstitel »Bezahlt« wieder auf (Tb, 29.9.1923), was im Juni 1924 zu einer ersten Niederschrift führt: »Dict. Bezahlt vorläufig zu Ende« (Tb, 16.6.1924).
[ "Texts and Concepts" ]
W3100010313
MAGNETOSPHERIC ACCRETION AND EJECTION OF MATTER IN RESISTIVE MAGNETOHYDRODYNAMIC SIMULATIONS
The ejection of matter in the close vicinity of a young stellar object is investigated, treating the accretion disk as a gravitationally bound reservoir of matter. By solving the resistive MHD equations in 2D axisymmetry using our version of the Zeus-3D code with newly implemented resistivity, we study the effect of magnetic diffusivity in the magnetospheric accretion-ejection mechanism. Physical resistivity was included in the whole computational domain so that reconnection is enabled by the physical as well as the numerical resistivity. We show, for the first time, that quasi-stationary fast ejecta of matter, which we call {\em micro-ejections}, of small mass and angular momentum fluxes, can be launched from a purely resistive magnetosphere. They are produced by a combination of pressure gradient and magnetic forces, in presence of ongoing magnetic reconnection along the boundary layer between the star and the disk, where a current sheet is formed. Mass flux of micro-ejection increases with increasing magnetic field strength and stellar rotation rate, and is not dependent on the disk to corona density ratio and amount of resistivity.
[ "Universe Sciences", "Fundamental Constituents of Matter" ]
320651
Solving High Energy Physics Equations using Monte Carlo Gaming Techniques
The main objective of this proposal is to perform (hitherto unsolved) calculations in Quantum Field Theory (QFT) most of which are urgently needed to make optimal use of upcoming experimental data from the Large Hadron Collider. These specific calculations have been intractable thus far due to their enormous demand of man and computer power. We will make use of the brand new technique of Monte Carlo Tree Search (MCTS) from the fields of Artificial Intelligence (AI) and gaming to resolve this issue and automatize the derivation of formulas and the construction of computer programs. To do so, we will first develop MCTS into a viable QFT tool. Calculations and derivation of the formulas will be done by the (open source) symbolic system FORM developed by the PI. A spinoff of the proposal will be the adaptation and extension of FORM to allow the physics and the AI to work well together. We will make the new technology available for other researchers, enabling a wide range of calculations at a new level of precision.
[ "Fundamental Constituents of Matter", "Computer Science and Informatics" ]
10.1016/j.msea.2015.08.060
Effect of grain size and specimen dimensions on micro-forming of high purity aluminum
Micro-compression testing was conducted using high purity Al processed by equal-channel angular pressing (ECAP) with both coarse-grained (CG) and ultrafine-grained (UFG) samples. The effects on the flow stresses of the initial grain size and the specimen size were investigated and the results show the initial grain sizes and the specimen dimensions affect the flow stresses during micro-compression for both CG and UFG specimens. There is a transition from strain hardening to strain softening with decreasing grain size during micro-compression but the transition grain size is dependent upon the size of the specimen. These results are interpreted using a model based on the separate influences of dislocation annihilation and dislocation accumulation in the UFG and CG materials, respectively. The results demonstrate that the occurrence of surface roughening is improved when using UFG pure Al and this shows there is a significant potential for using UFG pure Al in micro-forming operations.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1007/s11229-013-0261-9
A slugfest of intuitions: Contextualism and experimental design
This paper considers ways that experimental design can affect judgments about informally presented context shifting experiments. Reasons are given to think that judgments about informal context shifting experiments are affected by an exclusive reliance on binary truth value judgments and by experimenter bias. Exclusive reliance on binary truth value judgments may produce experimental artifacts by obscuring important differences of degree between the phenomena being investigated. Experimenter bias is an effect generated when, for example, experimenters disclose (even unconsciously) their own beliefs about the outcome of an experiment. Eliminating experimenter bias from context shifting experiments makes it far less obvious what the "intuitive" responses to those experiments are. After it is shown how those different kinds of bias can affect judgments about informal context shifting experiments, those experiments are revised to control for those forms of bias. The upshot of these investigations is that participants in the contextualist debate who employ informal experiments should pay just as much attention to the design of their experiments as those who employ more formal experimental techniques if they want to avoid obscuring the phenomena they aim to uncover.
[ "The Human Mind and Its Complexity" ]
10.1209/0295-5075/122/36006
Hydrogel Menisci Shape Interaction And Instability
The interface of a soft hydrogel is easily deformed when it is in contact with particles, droplets or cells. Here we compute the intricate shapes of hydrogel menisci due to the indentation of point particles. The analysis is based on a free energy formulation, by which we also assess the interaction laws between neighbouring particles on hydrogel interfaces, similar to the "Cheerios effect". It is shown how the meniscus formed around the particles results from a competition between surface tension, elasticity and hydrostatic pressure inside the gel. We provide a detailed overview of the various scaling laws, which are governed by a characteristic shear modulus G∗ √ = γpg that is based on surface tension γ and gravity pg. Stiffer materials exhibit a solid-like response while softer materials are more liquid-like. The importance of G∗ is further illustrated by examining the Rayleigh-Taylor instability of soft hydrogels.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1126/science.aal3298
Recent natural selection causes adaptive evolution of an avian polygenic trait
We used extensive data froma long-term study of great tits (Parusmajor) in theUnitedKingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirmthat these genes, especially the collagen gene COL4A5, explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.
[ "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1051/0004-6361/201937247
ALMA chemical survey of disk-outflow sources in Taurus (ALMA-DOT)
The chemical composition of planets is determined by the distribution of the various molecular species in the protoplanetary disk at the time of their formation. To date, only a handful of disks have been imaged in multiple spectral lines with high spatial resolution. As part of a small campaign devoted to the chemical characterization of disk-outflow sources in Taurus, we report on new ALMA Band 6 (~1. 3 mm) observations with ~0. 15′′ (20 au) resolution toward the embedded young star DG Tau B. Images of the continuum emission reveals a dust disk with rings and, putatively, a leading spiral arm. The disk, as well as the prominent outflow cavities, are detected in CO, H2CO, CS, and CN; instead, they remain undetected in SO2, HDO, and CH3OH. From the absorption of the back-side outflow, we inferred that the disk emission is optically thick in the inner 50 au. This morphology explains why no line emission is detected from this inner region and poses some limitations toward the calculation of the dust mass and the characterization of the inner gaseous disk. The H2CO and CS emission from the inner 200 au is mostly from the disk, and their morphology is very similar. The CN emission significantly differs from the other two molecules as it is observed only beyond 150 au. This ring-like morphology is consistent with previous observations and the predictions of thermochemical disk models. Finally, we constrained the disk-integrated column density of all molecules. In particular, we found that the CH3OH/H2CO ratio must be smaller than ~2, making the methanol non-detection still consistent with the only such ratio available from the literature (1. 27 in TW Hya).
[ "Physical and Analytical Chemical Sciences", "Universe Sciences" ]
802437
The Dark Side of Translation: 20th and 21st Century Translation from Russian as a Political Phenomenon in the UK, Ireland, and the USA
What is the dark side of translation? Translation is valued, taught, and often funded as a deterrent to monolingual nationalism and cultural parochialism. Yet the praxis of translation is highly politicized, often subverted by ideological prejudice or state interference. Translators have a personal agenda, as do editors, publishers, and other agents. Every translation is an act of cultural appropriation. This may not be detrimental to the culture of origin; even inaccurate translations can confer prestige on the former. The ‘dark side’ of translation – its immanent politics – often allows subaltern nations to assert cultural parity with larger neighbours. RusTRANS investigates how individuals, and governments, exploit this ‘dark side’ to reap cultural capital by translating their own literature into global languages (and the reverse). The PI and postdoctoral research assistant will research four case studies about translators of Russian literature, and their networks, in Anglophone contexts (Ireland, the UK, and the USA). Three doctoral students will study the transmission of Russian literature in other European cultures. We will also commission new translations of contemporary Russian writing in order to observe the dynamics of translator (and publisher) networks today. RusTRANS offers two key innovations. First, we explore an obscure, paradoxical, yet crucial function of translation: as a means of self-promotion and cultural consolidation for emergent nation-states. By focussing on literary translation, and on the transmission of a single language (Russian), we create a coherent paradigm for historians of the cultural reception of national literatures in translation. Second, our diachronic approach to translation praxis allows us to contrast past translation networks and strategies with cultural agents in the ever-more volatile context of modern Russia, as we document the political pressures placed on contemporary authors, translators, and publishers.
[ "Texts and Concepts", "The Study of the Human Past", "Studies of Cultures and Arts" ]
10.1371/journal.pone.0135353
Lack of dietary polyunsaturated fatty acids causes synapse dysfunction in the Drosophila visual system
Polyunsaturated fatty acids (PUFAs) are essential nutrients for animals and necessary for the normal functioning of the nervous system. A lack of PUFAs can result from the consumption of a deficient diet or genetic factors, which impact PUFA uptake and metabolism. Both can cause synaptic dysfunction, which is associated with numerous disorders. However, there is a knowledge gap linking these neuronal dysfunctions and their underlying molecular mechanisms. Because of its genetic manipulability and its easy, fast, and cheap breeding, Drosophila melanogaster has emerged as an excellent model organism for genetic screens, helping to identify the genetic bases of such events. As a first step towards the understanding of PUFA implications in Drosophila synaptic physiology we designed a breeding medium containing only very low amounts of PUFAs. We then used the fly's visual system, a well-established model for studying signal transmission and neurological disorders, to measure the effects of a PUFA deficiency on synaptic function. Using both visual performance and eye electrophysiology, we found that PUFA deficiency strongly affected synaptic transmission in the fly's visual system. These defects were rescued by diets containing omega-3 or omega-6 PUFAs alone or in combination. In summary, manipulating PUFA contents in the fly's diet was powerful to investigate the role of these nutrients on the fly's visual synaptic function. This study aims at showing how the first visual synapse of Drosophila can serve as a simple model to study the effects of PUFAs on synapse function. A similar approach could be further used to screen for genetic factors underlying the molecular mechanisms of synaptic dysfunctions associated with altered PUFA levels.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
W4301394117
USO DO PLASMA ATMOSFÉRICO A FRIO NO TRATAMENTO DO CARCINOMA DE CÉLULAS ESCAMOSAS FELINO EM ESTÁGIO AVANÇADO
INTRODUÇÃO: O plasma atmosférico frio (CAP) vem emergindo como tratamento promissor para o tratamento de lesões cutâneas, possuindo capacidade antimicrobiana e antinflamatória. Recentemente vem sendo utilizado no tratamento de neoplasias, promovendo a morte seletiva de células cancerígenas por meio da produção de espécies reativas de oxigênio e nitrogênio (ERON). Dentre os cânceres de pele não melanoma, o carcinoma de células escamosas (CCE) é o segundo mais prevalente, especialmente no nordeste do Brasil, onde há alta incidência solar. Os gatos são excelentes modelos para estudos de CCE, pois também frequentemente desenvolvem esse tipo de neoplasia, que possui comportamento semelhante. OBJETIVO: Dessa forma, objetivou-se avaliar o efeito do CAP sobre lesões de CCE em gato atendido no Hospital Veterinário Jerônimo Dix-Huit Rosado Maia – HOVET/UFERSA. MÉTODOS: Um felino, macho, adulto, com quatro lesões faciais (plano nasal, ponta da orelha, lábio inferior e canto medial do olho) foi submetido a dois ciclos de tratamento com CAP. Cada ciclo consistiu na administração do plasma por três vezes dentro de uma semana, seguido por uma semana sem exposição. O paciente foi acompanhado para avaliação da resposta ao tratamento e efeitos adversos. RESULTADOS: Com dois ciclos de tratamento foi possível observar resposta completa para as formações menores (canto medial do olho e ponta da orelha). O tumor em plano nasal apresentou resposta parcial e o CCE labial permaneceu estável. Os efeitos adversos foram leves, autolimitantes e incluíram eritema e formação de crostas. CONCLUSÃO: O CAP demonstrou-se eficaz para o tratamento do CCE cutâneo felino, principalmente em lesões superficiais. Para formações mais proliferativas, como em lábio inferior, podem ser necessárias estratégias multimodais de tratamento, a fim de permitir uma maior penetrabilidade das ERON.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1111/bjir.12053
Rule Enactment in a Pan-European Labour Market: Transnational Posted Work in the German Construction Sector
This article analyses the micro-level rule enactment of the posting of workers framework in the German construction sector. I examine how actors draw on different power resources in order to influence policies without formal negotiation within transnational workspaces and thereby initiate institutional change. Drawing on interviews with posted workers, managers, unionists, works councillors and labour inspectors I show how transnational subcontracting allows the emergence of different regulatory spaces at national and workplace level. The article concludes that the informal renegotiation of employment relations in transnational workspaces is likely to destabilize the posting framework negotiated at policy level.
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions" ]
323883
Personal Perception
The project aims to open-up a new research field concerned with how human visual perception operates in a social context, and involves an innovative link between cognitive and social psychology. In particular, the project assesses how personal social interests permeate the functional and neural processes supporting human visual perception. The proposal is built around emerging findings from my laboratory showing that it is possible to experimentally ‘tag’ stimuli with personal-related (e.g., self-linked) associations, which enhance subsequent stimulus processing. The tagged stimuli can then be used to probe specific functional stages and brain mechanisms mediating visual perception, taking us beyond the view of perception as a purely bottom-up module to a new view of perception as tuned to personal self-interest. The project will provide a coherent programme of research using inter-disciplinary and state-of-the-art methods to assess (i) which functional processes in perception are affected by self-related biases, (ii) whether the effects occur automatically and even prior to the engagement of visual attention; (iii) the neural substrates of these effects (the neural localization, connectivity and necessary role of different brain regions); (iv) how self-prioritization is modulated by culture, (v) the developmental trajectory of self-prioritization in perception (when does self-prioritized perception occur in children? are the critical factors the same as in adults? does self-prioritization in perception increase in older adults?) and (vi) what factors determine the effects (what are the causal drivers of self-prioritized perception? reward? shared values? empathy?). By marrying together research from perceptual and social psychology, the project will offer a new over-arching framework for conceptualising human perception in a social context, enabling us to understand for the first time how social salience can modulate the perceptual salience of stimuli.
[ "The Social World and Its Interactions", "The Human Mind and Its Complexity" ]
US 2004/0005096 W
COVALENT MODIFICATION OF RNA FOR IN VITRO AND IN VIVO DELIVERY
The post-synthetic modification of RNA for the delivery of the RNA to a mammalian cell is described. The modifications enhance resistant of the RNA to nuclease digestion and delivery of the RNA to the cell whether the RNA is delivered alone or in combination with a transfection agent. Activity of the RNA in the cell is maintained.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Biotechnology and Biosystems Engineering" ]
10.1093/gbe/evt205
Is ftsH the key to plastid longevity in sacoglossan slugs?
Plastids sequestered by sacoglossan sea slugs have long been a puzzle. Some sacoglossans feed on siphonaceous algae and can retain the plastids in the cytosol of their digestive gland cells. There, the stolen plastids (kleptoplasts) can remain photosynthetically active in some cases for months. Kleptoplast longevity itself challenges current paradigms concerning photosystem turnover, because kleptoplast photosystems remain active in the absence of nuclear algal genes. In higher plants, nuclear genes are essential for plastid maintenance, in particular, for the constant repair of the D1 protein of photosystem II. Lateral gene transfer was long suspected to underpin slug kleptoplast longevity, but recent transcriptomic and genomic analyses show that no algal nuclear genes are expressed from the slug nucleus. Kleptoplast genomes themselves, however, appear expressed in the sequestered state. Here we present sequence data for the chloroplast genome of Acetabularia acetabulum, the food source of the sacoglossan Elysia timida, which can maintain Acetabularia kleptoplasts in an active state for months. The data reveal what might be the key to sacoglossan kleptoplast longevity: plastids that remain photosynthetically active within slugs for periods of months share the property of encoding ftsH, a D1 quality control protease that is essential for photosystem II repair. In land plants, ftsH is always nuclear encoded, it was transferred to the nucleus from the plastid genome when Charophyta and Embryophyta split. A replenishable supply of ftsH could, in principle, rescue kleptoplasts from D1 photodamage, thereby influencing plastid longevity in sacoglossan slugs.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.gca.2014.06.037
Structure, equation of state and transport properties of molten calcium carbonate (CaCO<inf>3</inf>) by atomistic simulations
First-principle molecular dynamics (FPMD) calculations have been performed to evaluate the physical properties of liquid calcium carbonate (CaCO3), which are up to now poorly known. The liquid structure, the density, the atomic vibration motions, the diffusion coefficients of calcium and carbonate ions and the electrical conductivity have been evaluated. As compared with silicate melts, molten CaCO3 is characterized by a low density (~2. 25g/cm3 at 1623K and 0. 5GPa), a viscosity almost as low as that of water (~5mPas), and a high conductivity (~200S/m). In using the FPMD calculations for benchmark, an empirical force field has been developed for predicting the properties of molten CaCO3 at any state point in the liquid stability field. This force field is implemented into a classical molecular dynamics (MD) code, much cheaper in computer time, and the equation of state and the phase diagram of the liquid phase have been obtained. The evolutions of the self diffusion coefficients, viscosity, and the electrical conductivity with pressure and temperature have been investigated and the results fitted with analytical forms. It is shown that the Stokes-Einstein equation, expressing the viscosity as a function of diffusion motion, is well followed, and that the Nernst-Einstein equation relating the electrical conductivity to the diffusion coefficients of charge carriers leads to an accurate prediction of the conductivity, provided that a constant correcting factor is applied. Consequently, viscosity and electrical conductivity of the liquid are found to be anticorrelated with each other and can be described by a simple law; λ=A/η0. 9 (where A=1. 905, λ is in S/m, and η in Pas).
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1080/17531055.2020.1768468
One Stop Border Posts In East Africa State Encounters Of The Fourth Kind
Across Africa, One-Stop Border Posts are being rolled out as part of a continental/ regional integration agenda that seeks to facilitate the movement of people and goods. This article focuses on fo. . .
[ "Human Mobility, Environment, and Space", "Institutions, Governance and Legal Systems" ]
267104
Towards the Construction of the Fundamental Theory of Flavour
Six quarks and six leptons of different kinds, referred to as flavours, form the modern periodic table of the fundamental building blocks of matter. The Standard Model of particle physics successfully describes these elementary particles and the forces between them. A deeper understanding of the flavour structure of quarks and leptons, of their masses and couplings, is however still missing. Decisive new experiments are about to start in particle physics (LHC, high-intensity flavour facilities). They will test existing theoretical concepts and inspire new ideas. This should allow us to make substantial steps forwards in the construction of the fundamental Theory of Flavour, which is the main goal of this project. Such a theory should allow us to address the following fundamental questions: what is the underlying dynamics differentiating quarks and leptons of different flavour? Is this dynamics related to a new symmetry? How can this new dynamics be tested at low and high energies? These questions are of utmost importance in the context of our search for a new, more fundamental, theory of elementary interactions. They are also key ingredients to understand the strucutre of our Universe. Reaching this goal requires substantial efforts in model building, precision calculations, and phenomenological studies. These different lines of research will be joined in a novel way by the collaboration of the principal investigator with four younger team members. All team members have made, mostly independently, important and often pioneering contributions to the different aspects of this project. The combination of their different expertise in a joint effort is a unique feature of the present proposal.
[ "Fundamental Constituents of Matter" ]
10.1039/c7ta03144k
Correlating photovoltaic properties of a PTB7-Th:PC71BM blend to photophysics and microstructure as a function of thermal annealing
The effect of thermal annealing on a polymer solar cell is investigated and related to changes in the photophysics and structure.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1093/cercor/bhs142
Functional neural plasticity and associated changes in positive affect after compassion training
The development of social emotions such as compassion is crucial for successful social interactions as well as for the maintenance of mental and physical health, especially when confronted with distressing life events. Yet, the neural mechanisms supporting the training of these emotions are poorly understood. To study affective plasticity in healthy adults, we measured functional neural and subjective responses to witnessing the distress of others in a newly developed task (Socio-affective Video Task). Participants' initial empathic responses to the task were accompanied by negative affect and activations in the anterior insula and anterior medial cingulate cortex-a core neural network underlying empathy for pain. Whereas participants reacted with negative affect before training, compassion training increased positive affective experiences, even in response to witnessing others in distress. On the neural level, we observed that, compared with a memory control group, compassion training elicited activity in a neural network including the medial orbitofrontal cortex, putamen, pallidum, and ventral tegmental area-brain regions previously associated with positive affect and affiliation. Taken together, these findings suggest that the deliberate cultivation of compassion offers a new coping strategy that fosters positive affect even when confronted with the distress of others.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity" ]
10.1103/PhysRevC.86.035801
Investigation of α-induced reactions on 127I for the astrophysical γ process
Background: The γ process in core-collapse supernova explosions is thought to explain the origin of proton-rich isotopes between Se and Hg, the so-called p nuclei. The majority of the reaction rates for γ process reaction network studies has to be predicted in Hauser-Feshbach statistical model calculations. Recent investigations have shown problems in the prediction of α widths at astrophysical energies. This impacts the reliability of abundance predictions in the upper mass range of the p nuclei. Purpose: Our purpose is to measure the 127I(α,γ)131I and 127I(α,n)130I reaction cross sections close to the astrophysically relevant energy range to test the predictions, to derive an improved reaction rate, and to extend the database required to define an improved global optical α+nucleus potential. Methods: The cross sections are derived using the activation technique and the yield of the emitted γ, and characteristic x-ray photons are measured using a LEPS and an HPGe detector. Results: Cross sections of the 127I(α,γ)131Cs reaction are determined for the first time, at energies 9. 50≤Ec. m. ≤15. 15 MeV. The 127I(α,n)130Cs reaction is studied in the range 9. 62≤Ec. m. ≤15. 15 MeV. Furthermore, the relative intensity of the 536. 1-keV γ transition is measured precisely; its uncertainty is reduced from 13% to 4%. The results are then compared to Hauser-Feshbach calculations which are also used to extend the cross sections into the astrophysically relevant region and to compute the reaction rate. Conclusions: The comparison to statistical Hauser-Feshbach model calculations shows that the α width can be described well in the measured energy range using a standard, energy-independent global optical potential. The newly derived stellar reaction rates at γ process temperatures for 127I(α,γ)131I and its reverse reactions, nevertheless, are faster by factors of 4-10 than those from previous calculations, owing to further improvements in the reaction model. The importance of the inclusion of complete level schemes in the Hauser-Feshbach calculations is illustrated by comparing the impacts of two level schemes, one of them extending to higher excitation energies but not containing all relevant levels.
[ "Fundamental Constituents of Matter", "Universe Sciences" ]
10.1021/acs.chemmater.5b03995
Controlled Shape and Nucleation Switching of Interfacially Polymerizable Nanoassemblies by Methyl Substitution
Interfacial polymerization of uniform template-free nanostructures is very challenging since many factors play determinant roles in the final structure of the resulting nanoassemblies. Here, we present a single oxidative coupling method for the synthesis of different nanoshapes by addition or substitution of a methyl group on aniline monomers to freely alter the mechanism of monomer-to-polymer conversion. Well-defined nanotubes, nanohollows, and solid nanospheres are obtained from aniline, N-methylaniline, and 2-methylaniline polymerizations, respectively. We found that the extent of hydrophobicity and protonation under mild acidic conditions determines the monomers' arrangement in micelle or droplet form, reactivity, and nucleation mechanism. These can subsequently affect the final morphology through a fusion process to form tubular structures, external flux of monomers to form nanohollows, and intradroplet oxidation to form solid nanospheres. Altered biological responses, such as cytocompatibility, redox response, hemocompatibility, and cell proliferation, are also found to be dependent on the position of the methyl group in the nanostructures.
[ "Physical and Analytical Chemical Sciences", "Materials Engineering", "Synthetic Chemistry and Materials" ]
10.1021/jacs.6b03604
Advancing Drug Formulation Additives toward Precision Additives with Release Mediating Peptide Interlayer
Amphiphilic drug formulation additives based on palmitic acid-modified poly(ethylene glycol) (Pal-PEG) are combined with a tailored drug binding peptide that is positioned at the hydrophobic-hydrophilic interface. The peptide originates from combinatorial selection and enables precise modulation of the drug release profiles. While Pal provides a cost-effective reservoir for drug storage, the PEG realizes solubility and shielding. The precision additives reach high payloads close to 1:1, rendering a photosensitizer water-soluble and providing adjustable drug activation kinetics by fine-tuning the peptide interface layer.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1111/pai.12344
Maternal preeclampsia and childhood asthma in the offspring
Background: Preeclampsia is a possible risk factor for childhood asthma in the offspring. Our aim was to find whether preeclampsia is associated with childhood asthma. We also aimed to study whether a possible association can be explained by factors shared by siblings. Methods: All eligible live singletons born in Denmark during 1993-2007 were identified (N = 923,533), and the occurrence of preeclampsia during the index pregnancy was determined. The children were followed from their 3rd birthday to the first hospitalization, outpatient contact or prescription for asthma, emigration, death, their 18th birthday, or the end of 2010, whichever came first. We carried out a nested case-control and a case-sibling study with density sampling to estimate incidence rate ratio (IRR) of asthma as a function of maternal preeclampsia, using conditional logistic regression. Results: A total of 115,522 asthma cases were identified during 1996-2010. In the case-control analysis, the overall IRR of asthma for those exposed to maternal preeclampsia was 1. 19 (95% confidence interval (CI): 1. 15, 1. 24). The IRRs for asthma according to early and late onset preeclampsia were 1. 88 (95% CI: 1. 67, 2. 11) and 1. 14 (95% CI: 1. 10, 1. 19). In the case-sibling analysis, the corresponding IRRs were 1. 06 (95% CI: 0. 98, 1. 14), 1. 15 (95% CI: 1. 02, 1. 29), and 1. 02 (95% CI: 0. 93, 1. 11), respectively. Conclusions: Early onset preeclampsia was associated with an increased risk of asthma in the offspring, but part of this association may be due to confounding by factors shared by siblings.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physiology in Health, Disease and Ageing" ]
Q77907
Development of the Cybersecurity System of Internet Services as a tool to improve the security of use of Internet services by end-users.
Reference number of the aid programme: SA.41471(2015/X) Purpose of public aid: Article 25 of EC Regulation No 651/2014 of 17 June 2014 declaring certain types of aid compatible with the internal market in the application of Articles 107 and 108 of the Treaty (OJ L. I'm sorry. EU L 187/1 of 26.06.2014). The aim of the project is to carry out R & D work on the development of the Cybersecurity System of Internet Services (SCSI), which significantly improves the security of end-users of Internet services. The technology is at the second level of technological readiness – the desired functionalities of the system and their application have been defined, taking as a starting point the protection of the user interface (UIP). Ultimately, we will create a prototype of the system and validate it in real warunaks by integration with the website of the partner, which will allow to obtain the IX level of readiness. In 2017, Gartner included the trend related to protection against attacks against users, including Gartner, pointing to a niche in the development of cybersecurity, i.e. User Interface Protection (UIP). This is linked to the pursuit of a layer in Internet services to protect against specific attacks of business logic. The competition analysis confirms the lack of efficient and effective solutions based on this concept. Effective protection of end-users’ data is crucial in the light of legal changes. IT’S A GDPR. The result of the project will be a product innovation. It will be a solution to protect users from man-in-the-Browser (MitB) and Man-in-the-Middle (MITM) attack vectors to respond to demand, in particular among: banks, online lending companies, hosting companies and VOD networks. It will be distinguished by its approach to protection against cyber attacks on websites aimed at unauthorised change of displayed content on the user’s side or theft of data.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1051/0004-6361/201834489
Formation Of Planetary Systems By Pebble Accretion And Migration Growth Of Gas Giants
Giant planets migrate though the protoplanetary disc as they grow. We investigate how the formation of planetary systems depends on the radial flux of pebbles through the protoplanetary disc and on the planet migration rate. Our N-body simulations confirm previous findings that Jupiter-like planets in orbits outside the water ice line originate from embryos starting out at 20-40 AU when using nominal type-I and type-II migration rates and a pebble flux of 100-200 Earth masses per million years, enough to grow Jupiter within the lifetime of the solar nebula. The planetary embryos placed up to 30AU migrate into the inner system (r<1AU) and form super-Earths or hot and warm gas giants, producing systems that are inconsistent with the configuration of the solar system, but consistent with some exoplanetary systems. We also explore slower migration rates which allow the formation of gas giants from embryos originating from the 5-10AU region, which are stranded exterior to 1 AU at the end of the gas-disc phase. We identify a pebble flux threshold below which migration dominates and moves the planetary core to the inner disc, where the pebble isolation mass is too low for the planet to accrete gas efficiently. Giant planet growth requires a sufficiently-high pebble flux to enable growth to out-compete migration. Even higher pebble fluxes produce systems with multiple gas giants. We show that planetary embryos starting interior to 5AU do not grow into gas giants, even if migration is slow and the pebble flux is large. Instead they grow to the mass regime of super-Earths. This stunted growth is caused by the low pebble isolation mass in the inner disc and is independent of the pebble flux. Additionally we show that the long term evolution of our formed planetary systems can produce systems with hot super-Earths and outer gas giants as well as systems of giants on eccentric orbits (abridged).
[ "Universe Sciences" ]
10.1007/JHEP04(2015)019
Holographic Charge Oscillations
The Reissner-Nordstrom black hole provides the prototypical description of a holographic system at finite density. We study the response of this system to the presence of a local, charged impurity. Below a critical temperature, the induced charge density, which screens the impurity, exhibits oscillations. These oscillations can be traced to the singularities in the density-density correlation function moving in the complex momentum plane. At finite temperature, the oscillations are very similar to the Friedel oscillations seen in Fermi liquids. However, at zero temperature the oscillations in the black hole background remain exponentially damped, while Friedel oscillations relax to a power-law
[ "Condensed Matter Physics", "Fundamental Constituents of Matter" ]
10.1037/a0025659
Automated gaze-contingent objects elicit orientation following in 8-month-old infants
The current study tested whether the purely amodal cue of contingency elicits orientation following behavior in 8-month-old infants. We presented 8-month-old infants with automated objects without human features that did or did not react contingently to the infants' fixations recorded by an eye tracker. We found that an object's occasional orientation toward peripheral targets was reciprocated by a congruent visual orientation following response by infants only when it had displayed gaze-contingent interactivity. Our finding demonstrates that infants' gaze-following behavior does not depend on the presence of a human being. The results are consistent with the idea that, in 8-month-old infants, the detection of contingent reactivity, like other communicative signals, can itself elicit the illusion of being addressed.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity" ]
W2896274961
Design and Operation Overview of 4-person 180-day Integrated Experiment in Controlled Ecological Life Support System
Objective To explore the key technologies of integrated bio-regenerative and physical-chemical regenerative life support system,and investigate the performance of the Controlled Ecological Life Support System( CELSS) with multiple crews in long-term experiment,and to meet the engineering demands of life support system application in extraterrestrial base. Methods A closed ecological-cycle experiment platform with environment control,material-circulation and life support application was established. Based on the CELSS platform,this study assessed the material-circulation and its dynamic balance regulation when the life support function changed from physical-chemical regeneration to bio-regeneration through 40 d simulated and 180 d manned experiments. Results The long-term results of total 220 d experiments indicated that the environment parameters were controlled under the safe level,and the effective and independent control of the environment for crew and plant survival was achieved. During the 180 d manned experiment,the material-circulation kept at a steady state and achieved high-effective regeneration rate,including 100% atmospheric and 100% water regeneration rate,55% food closure rate and 87. 7% solid waste recycle rate. Conclusion The long-term integrated experiment verified the entire process of CELSS integrated technologies,covering design,construction and operation. It accumulated valuable engineering experience for the future technology development and application.
[ "Products and Processes Engineering", "Biotechnology and Biosystems Engineering", "Earth System Science" ]
10.1016/j.celrep.2016.11.012
Tenascin-C Orchestrates Glioblastoma Angiogenesis by Modulation of Pro- and Anti-angiogenic Signaling
High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis. Glioblastoma cells exposed to tenascin-C secrete pro-angiogenic factors that promote endothelial cell survival and tubulogenesis. Proteomic analysis of their secretome reveals a signature, including ephrin-B2, that predicts decreased survival of glioma patients. We find that ephrin-B2 is an important pro-angiogenic tenascin-C effector. Thus, we demonstrate dual activities for tenascin-C in glioblastoma angiogenesis and uncover potential targeting and prediction opportunities.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1016/j.lingua.2015.10.002
Pyow-hack revisited: Two analyses of Putty-nosed monkey alarm calls
Male Putty-nosed monkeys have two main alarm calls, pyows and hacks. While pyows have a broad distribution suggestive of a general call, hacks are often indicative of eagles. In a series of articles, Arnold and Zuberbühler showed that Putty-nosed monkeys sometimes produce distinct pyow-hack sequences made of a small number of pyows followed by a small number of hacks; and that these are predictive of group movement. Arnold and Zuberbühler claimed that pyow-hack sequences are syntactically combinatorial but not semantically compositional because their meaning cannot be derived from the meanings of their component parts. We compare two theories of this phenomenon. One formalizes and modifies the non-compositional theory. The other presents a semantically compositional alternative based on weak meanings for pyow (‘general alarm’) and hack (‘non-ground movement’), combined with pragmatic principles of competition; a crucial one is an ‘Urgency Principle’ whereby calls that provide information about the nature/location of a threat must come before calls that do not. Semantically, pyow-hack sequences are compatible with any kind of situation involving (moving) aerial predators or (arboreal) movement of the monkeys themselves. But in the former case, hacks provide information about the location of a threat, and hence should appear at the beginning of sequences. As a result, pyow-hack sequences can only be used for non-threat-related situations involving movement, hence a possible inference that they involve group movement. Without adjudicating the debate, we argue that a formal analysis can help clarify competing theories and derive new predictions that might decide between them.
[ "The Human Mind and Its Complexity", "Environmental Biology, Ecology and Evolution" ]
W1990519231
Preparation and Photocatalytic Properties of Nano Ni/TiO<sub>2</sub> Composite in Alginate
New nano nickel-doped titanium dioxide composites had been produced by a conducting sol-gel method. The alginate gel was used as a template to prevent the conglomeration of the inorganic materials. In this experiment, nickel nitrate, tetrabutyl titanate and sodium alginate were used as main materials to prepare different amount nickel-doped TiO 2 particles. The amount of Ni was studied from 0 to 9 mol.-% (where mol.-% refers to the Ni/TiO 2 molar ratio), and the Ni/TiO 2 composites were characterized by XRD, FT-IR, TG-DTA, and we carried out doping amount, catalyst amount and illumination time influence on photocatalytic performance of nano Ni/TiO 2 composite in aqueous methyl orange. The activity of TiO 2 gradually increased with the increasing of doping amount, and there was highest catalytic efficiency when Ni = 9 % mol.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1371/journal.ppat.1005585
Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets
Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro β-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the β-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1. 9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore β-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Immunity, Infection and Immunotherapy", "Prevention, Diagnosis and Treatment of Human Diseases", "Physical and Analytical Chemical Sciences" ]
10.3791/3453
Electric Field Controlled Directed Migration Of Neural Progenitor Cells In 2D And 3D Environments
Endogenous electric fields (EFs) occur naturally in vivo and play a critical role during tissue/organ development and regeneration, including that of the central nervous system1,2. These endogenous EFs are generated by cellular regulation of ionic transport combined with the electrical resistance of cells and tissues. It has been reported that applied EF treatment can promote functional repair of spinal cord injuries in animals and humans3,4. In particular, EF-directed cell migration has been demonstrated in a wide variety of cell types5,6, including neural progenitor cells (NPCs)7,8. Application of direct current (DC) EFs is not a commonly available technique in most laboratories. We have described detailed protocols for the application of DC EFs to cell and tissue cultures previously5,11. Here we present a video demonstration of standard methods based on a calculated field strength to set up 2D and 3D environments for NPCs, and to investigate cellular responses to EF stimulation in both single cell growth conditions in 2D, and the organotypic spinal cord slice in 3D. The spinal cordslice is an ideal recipient tissue for studying NPC ex vivo behaviours, post-transplantation, because the cytoarchitectonic tissue organization is well preserved within these cultures9,10. Additionally, this ex vivo model also allows procedures that are not technically feasible to track cells in vivo using time-lapse recording at the single cell level. It is critically essential to evaluate cell behaviours in not only a 2D environment, but also in a 3D organotypic condition which mimicks the in vivo environment. This system will allow high-resolution imaging using cover glass-based dishes in tissue or organ culture with 3D tracking of single cell migration in vitro and ex vivo and can be an intermediate step before moving onto in vivo paradigms.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration" ]
W2193870916
Improving neural network performance on SIMD architectures
Neural network calculations for the image recognition problems can be very time consuming. In this paper we propose three methods of increasing neural network performance on SIMD architectures. The usage of SIMD extensions is a way to speed up neural network processing available for a number of modern CPUs. In our experiments, we use ARM NEON as SIMD architecture example. The first method deals with half float data type for matrix computations. The second method describes fixed-point data type for the same purpose. The third method considers vectorized activation functions implementation. For each method we set up a series of experiments for convolutional and fully connected networks designed for image recognition task.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1109/TIA.2017.2704908
On Secondary Control Approaches For Voltage Regulation In Dc Microgrids
Centralized or decentralized secondary controller is commonly employed to regulate the voltage drop raised by the primary controller. However, in the case of high capacity microgrids (MGs) and long feeders with much voltage drop on the line resistances, the conventional methods may not guarantee the voltage regulation on the load busses within a suitable range. Therefore, in addition to compensate the voltage drop of the primary controller, it is necessary to regulate the voltage of critical loads. In this paper, a new voltage regulation strategy is proposed to regulate the voltage of MG by employing the average voltage of identified critical busses, which are determined by the proposed modal analysis. Numerical steady-state analysis and preliminary simulation results validate effectiveness of the proposed scheme. Furthermore, experimental results are performed to demonstrate the viability of the proposed approach.
[ "Systems and Communication Engineering", "Products and Processes Engineering" ]
10.1039/C4FD00195H
Unfolding The Contents Of Sub Nm Plasmonic Gaps Using Normalising Plasmon Resonance Spectroscopy
Plasmonic coupling of gold nanoparticles to a gold surface creates intense plasmonic hot spots with large electromagnetic field-enhancements within the cavity formed by the two metallic surfaces. The localised field in such structures is extremely sensitive to morphological fluctuations and subtle changes in the dielectric properties of the cavity contents. Here, we present an optical method that pins down the properties of the gap contents with high sensitivity, termed normalising plasmon resonance (NPR) spectroscopy. We use this on a variety of ultrathin molecular spacers such as filled and empty cucurbiturils, and graphene. Clear differences in the spectral positions and intensities of plasmonic modes observed in the scattering spectrum resolve thickness differences of 0. 1 nm, and refractive index changes from molecular filling.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1016/j.jenvp.2017.03.001
Predictors of visual attention to climate change images: An eye-tracking study
Attentional engagement with climate change is an important precondition for intentional climate-friendly behavior. However, not much is known about the determinants of an individuals’ implicit willingness to attend to this global problem. This study investigates two potentially relevant predictors of implicit attention to climate change: a) pro-environmental orientation as a trait factor and b) experimentally induced stress as a state factor. We expected positive effects of pro-environmental orientation and negative effects of stress. Seventy-one male participants with either high or low pro-environmental orientation were randomly assigned to a stress or control condition. Afterwards, they viewed a series of climate change images and negative control images, which were presented simultaneously with positive and neutral distractors. Attentional deployment to the different stimulus categories was assessed using eye-tracking technology. Participants with high pro-environmental orientation spent more time looking at climate change as well as other negative images, compared to participants with low pro-environmental orientation. This result suggests that pro-environmental individuals might be characterized by a general propensity to attend to negative information. Furthermore, stress reduced attentional deployment to both climate change and negative control images, which might indicate decreased interest in self-transcendent problems and/or increased efforts of emotion regulation under stress. In summary, these findings constitute first evidence for trait and state predictors of attentional engagement with climate change.
[ "The Human Mind and Its Complexity", "Earth System Science" ]
W1574263887
Non-negative Hidden Markov Modeling of Audio with Application to Source Separation
In recent years, there has been a great deal of work in modeling audio using non-negative matrix factorization and its probabilistic counterparts as they yield rich models that are very useful for source separation and automatic music transcription. Given a sound source, these algorithms learn a dictionary of spectral vectors to best explain it. This dictionary is however learned in a manner that disregards a very important aspect of sound, its temporal structure. We propose a novel algorithm, the non-negative hidden Markov model (N-HMM), that extends the aforementioned models by jointly learning several small spectral dictionaries as well as a Markov chain that describes the structure of changes between these dictionaries. We also extend this algorithm to the non-negative factorial hidden Markov model (N-FHMM) to model sound mixtures, and demonstrate that it yields superior performance in single channel source separation tasks.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1039/c5sm01429h
Shear banding in entangled polymers in the micron scale gap: a confocal-rheoscopic study
Recent shear experiments in well-entangled polymer solutions demonstrated that interfacial wall slip is the only source of shear rate loss and there is no evidence of shear banding in the micron scale gap.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1111/j.1365-2486.2012.02701.x
Comprehensive methodological analysis of long-term changes in phenological extremes in Germany
This study reports on alterations in the magnitude and frequency of extremes in reproductive phenology using long-term records (1951-2008) for plant species widely distributed across Germany. For each of fourteen indicator phases studied, time series of annual onset dates at up to 119 stations, providing 50-58 years of observation, were standardized by their station mean and standard deviation. Four alternative statistical models were applied and compared to derive probabilities of extreme early or late onset times for the phases: (1) Gaussian models were used to describe decadal probabilities of standardized anomalies, defined by data either falling below the 5th or exceeding the 95th percentile. (2) Semi-parametric quantile regression was employed for flexible and robust modelling of trends in different quantiles of onset dates. (3) Generalized extreme value distributions (GEV) were fitted to annual detrended minima and maxima of standardized anomalies, and (4) Generalized Pareto distributions (GPD) were fitted to extremes defined as peaks over threshold. Probabilities of extreme early phenological events inferred from Gaussian models, increased on average from 3 to 12%, whereas probabilities of extreme late phenological events decreased from 6 to 2% over the study period. Based on quantile regressions, summer and autumn phases revealed a more pronounced advancing pattern than spring phases. Estimated return levels by GEV were similar for the GPD methods, indicating that extreme early phenological events of magnitudes 2. 5, 2. 8, and 3. 6 on the detrended standardized anomaly scale would occur every 20 years for spring, summer and autumn phases, respectively. This corresponds to absolute onset advances of up to 2 months depending on the season and species. This study demonstrates how extreme phenological events can be accurately modelled even in cases of inherently small numbers of observations, and underlines the need for additional evaluation related to their impacts on ecosystem functioning.
[ "Earth System Science", "Environmental Biology, Ecology and Evolution", "Mathematics" ]
10.1177/0956797617714828
Reciprocity Outperforms Conformity To Promote Cooperation
Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants’ cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one’s reputation—a finding that supports a reciprocity framework.
[ "The Human Mind and Its Complexity", "The Social World and Its Interactions" ]
EP 2020077986 W
LOG GRAB
The present invention relates to the geometrical shape of a grab, a single grab element (one-element grab) thereof in the form of a solid and/or a hollow profile engaging in a closed grab element. The invention is used predominantly in timber processing.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1039/B810669J
Reversible Electronic Energy Transfer A Means To Govern Excited State Properties Of Supramolecular Systems
A strategy to manage energy, following light absorption, and modulate excited-state properties, including luminescence lifetimes of multicomponent photoactive systems, is presented. The intervening mechanism, which is illustrated through the use of bi-/multi-chromophoric molecules, relies on energy shuttling between different matched chromophores under kinetic and thermodynamic control. This tutorial review is destined to show supramolecular and materials chemists, spectroscopists and nanoscientists how to harness reversible electronic energy transfer in a predictable fashion in designer molecule-based systems.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1007/s00425-018-2989-4
LAESI mass spectrometry imaging as a tool to differentiate the root metabolome of native and range-expanding plant species
Main conclusion: LAESI-MSI, an innovative high-throughput technique holds a unique potential for untargeted detection, profiling and spatial localization of metabolites from intact plant samples without need for extraction or extensive sample preparation. Our understanding of chemical diversity in biological samples has greatly improved through recent advances in mass spectrometry (MS). MS-based-imaging (MSI) techniques have further enhanced this by providing spatial information on the distribution of metabolites and their relative abundance. This study aims to employ laser-ablation electrospray ionization (LAESI) MSI as a tool to profile and compare the root metabolome of two pairs of native and range-expanding plant species. It has been proposed that successful range-expanding plant species, like introduced exotic invaders, have a novel, or a more diverse secondary chemistry. Although some tests have been made using aboveground plant materials, tests using root materials are rare. We tested the hypothesis that range-expanding plants possess more diverse root chemistries than native plant species. To examine the root chemistry of the selected plant species, LAESI-MSI was performed in positive ion mode and data were acquired in a mass range of m/z 50–1200 with a spatial resolution of 100 µm. The acquired data were analyzed using in-house scripts, and differences in the spatial profiles were studied for discriminatory mass features. The results revealed clear differences in the metabolite profiles amongst and within both pairs of congeneric plant species, in the form of distinct metabolic fingerprints. The use of ambient conditions and the fact that no sample preparation was required, established LAESI-MSI as an ideal technique for untargeted metabolomics and for direct correlation of the acquired data to the underlying metabolomic complexity present in intact plant samples.
[ "Physical and Analytical Chemical Sciences", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W34812821
Findings with AVC Design for Mitigation of Human Induced Vibrations in Office Floors
In recent years, there have been extensive active vibration control (AVC) studies for the mitigation of human induced vibrations in a series of office floors, in which such vibrations are deemed to be ‘problematic’ and have been found to affect only certain sections of the floors. These floors are predominantly open-plan in layout and comprise of different structural configurations for their respective bays and this influences their dynamic characteristics. Most of the AVC studies have comprised extensive analytical predictions and experimental implementations of different controller schemes. The primary measures of vibration mitigation performance have been by frequency response function (FRF) measurements, responses to controlled walking tests, and in-service monitoring, all tests with and without AVC.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
10.1038/nchembio.2380
Engineering protein stability with atomic precision in a monomeric miniprotein
Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i. e. , changing three solvent-exposed hydroxyl groups to protons, reduces the TM to 20 °C. We attribute this result to the loss of CH-π interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with nonproteinogenic side chains. In analyses of natural protein structures, we find a preference for proline-tyrosine interactions over other proline-containing pairs, and observe abundant CH-π interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.18632/oncotarget.12002
Large variety in a panel of human colon cancer organoids in response to EZH2 inhibition
EZH2 inhibitors have gained great interest for their use as anti-cancer therapeutics. However, most research has focused on EZH2 mutant cancers and recently adverse effects of EZH2 inactivation have come to light. To determine whether colorectal cancer cells respond to EZH2 inhibition and to explore which factors influence the degree of response, we treated a panel of 20 organoid lines derived from human colon tumors with different concentrations of the EZH2 inhibitor GSK126. The resulting responses were associated with mutation status, gene expression and responses to other drugs. We found that the response to GSK126 treatment greatly varied between organoid lines. Response associated with the mutation status of ATRX and PAX2, and correlated with BIK expression. It also correlated well with response to Nutlin-3a which inhibits MDM2-p53 interaction thereby activating p53 signaling. Sensitivity to EZH2 ablation depended on the presence of wild type p53, as tumor organoids became resistant when p53 was mutated or knocked down. Our exploratory study provides insight into which genetic factors predict sensitivity to EZH2 inhibition. In addition, we show that the response to EZH2 inhibition requires wild type p53. We conclude that a subset of colorectal cancer patients may benefit from EZH2-targeting therapies.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1145/2661229.2661236
Dual Strip Weaving Interactive Design Of Quad Layouts Using Elastica Strips
We introduce Dual Strip Weaving, a novel concept for the interactive design of quad layouts, i. e. partitionings of freeform surfaces into quadrilateral patch networks. In contrast to established tools for the design of quad layouts or subdivision base meshes, which are often based on creating individual vertices, edges, and quads, our method takes a more global perspective, operating on a higher level of abstraction: the atomic operation of our method is the creation of an entire cyclic strip, delineating a large number of quad patches at once. The global consistency-preserving nature of this approach reduces demands on the user's expertise by requiring less advance planning. Efficiency is achieved using a novel method at the heart of our system, which automatically proposes geometrically and topologically suitable strips to the user. Based on this we provide interaction tools to influence the design process to any desired degree and visual guides to support the user in this task.
[ "Computer Science and Informatics" ]
10.1142/S0218301318300035
Tmd Gluon Distributions At Small X In The Cgc Theory
In this paper, we review recent progress in the description of unpolarized transverse-momentum-dependent (TMD) gluon distributions at small x in the color glass condensate (CGC) effective theory. We discuss the origin of the nonuniversality of TMD gluon distributions in the TMD factorization framework and in the CGC theory and the equivalence of the two approaches in their overlapping domain of validity. We show some applications of this equivalence, including recent results on the behavior of TMD gluon distributions at small x, and on the study of gluon saturation. We discuss recent advances in the unification of the TMD evolution and the nonlinear small-x evolution of gluon distributions.
[ "Fundamental Constituents of Matter" ]
10.1016/j.jbiotec.2014.04.005
Small RNA cloning and sequencing strategy affects host and viral microRNA expression signatures
The establishment of the microRNA (miRNA) expression signatures is the basic element to investigate the role played by these regulatory molecules in the biology of an organism. Marek's disease virus 1 (MDV-1) is an avian herpesvirus that naturally infects chicken and induces T cells lymphomas. During latency, MDV-1, like other herpesviruses, expresses a limited subset of transcripts. These include three miRNA clusters. Several studies identified the expression of virus and host encoded miRNAs from MDV-1 infected cell cultures and chickens. But a high discrepancy was observed when miRNA cloning frequencies obtained from different cloning and sequencing protocols were compared. Thus, we analyzed the effect of small RNA library preparation and sequencing on the miRNA frequencies obtained from the same RNA samples collected during MDV-1 infection of chicken at different steps of the oncoviral pathogenesis. Qualitative and quantitative variations were found in the data, depending on the strategy used. One of the mature miRNA derived from the latency-associated-transcript (LAT), mdv1-miR-M7-5p, showed the highest variation. Its cloning frequency was 50% of the viral miRNA counts when a small scale sequencing approach was used. Its frequency was 100 times less abundant when determined through the deep sequencing approach. Northern blot analysis showed a better correlation with the miRNA frequencies found by the small scale sequencing approach. By analyzing the cellular miRNA repertoire, we also found a gap between the two sequencing approaches. Collectively, our study indicates that next-generation sequencing data considered alone are limited for assessing the absolute copy number of transcripts. Thus, the quantification of small RNA should be addressed by compiling data obtained by using different techniques such as microarrays, qRT-PCR and NB analysis in support of high throughput sequencing data. These observations should be considered when miRNA variations are studied prior addressing functional studies.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Immunity, Infection and Immunotherapy" ]