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W2019319022
Emulsifying and Foaming Properties of Defatted Soy Meal Extracts Obtained by Subcritical Water Treatment
Soy meal from vegetable oil processing was treated with subcritical water at different temperatures (100, 125, 150, 175, 200, 225 and 250°C) for 5 min in a batch-type reactor. Maximum protein and carbohydrate contents in the liquid extracts were obtained at 225°C (0.52 ± 0.03 g/g of sample) and 175°C (0.24 ± 0.03 g/g of sample), respectively. The extracts from all treated temperatures similarly formed and stabilized oil-in-water type emulsion. However, the extracts at different temperatures showed different foaming capacities during 3 h of storage. Because of a short extraction time of the process, subcritical water treatment is a promising technology for producing functional substances from this industrial by-product.
[ "Products and Processes Engineering", "Physical and Analytical Chemical Sciences" ]
678674
Quantum fluids of photons in optically-induced structures
A variety of classical optical systems exhibiting rich and complex matter-like behavior have been explored in recent years. Unfortunately in the optical regime, photons – the fundamental constituents of light – do not interact strongly with one another, and therefore cannot be used for studying many-body effects. It is only in the extreme regime of quantum nonlinear optics where effective interactions between photons are made strong. In an atomic gas, strong long-range interactions can be achieved by coupling photons to interacting atoms. First experiments have indicated the formation of a two-photon bound state via this mechanism. The main goal of the proposed research is to develop an optical system based on atomic interactions that realizes quantum many-body physics with optical photons subject to a rich variety of model problems. The proposed method relies on reconfigurable, optically-induced, three-dimensional, structures, which are fully compatible with the underlying atomic process. These structures enable the spatial compression of photons for enhancing the interactions, wave guiding for one-dimensional confinement in long media, and a rich variety of two-dimensional potentials with tunable interactions, from nearly-free photons to various tight-binding models with a controllable level of disorder. Optically-induced structures also offer advantages to optical quantum information, enabling better gate fidelities due to stronger nonlinearities and multimode coupling for processes such as photon routing. Our method has the potential to realize quantum gases and fluids of interacting photons. We can manipulate the effective mass and the band structure, control the potential landscape, and tune the scattering length in the system from attractive to repulsive. In particular, we intend to study few-photon bound states, quantum solitons, Luttinger liquids of photons, and Wigner crystallization in one and two dimensions.
[ "Fundamental Constituents of Matter", "Condensed Matter Physics", "Systems and Communication Engineering" ]
10.1088/0004-637X/814/1/24
The Corona Of The Broad Line Radio Galaxy 3C 390 3
We present the results from a joint Suzaku/NuSTAR broadband spectral analysis of 3C 390. 3. The high quality data enables us to clearly separate the primary continuum from the reprocessed components allowing us to detect a high energy spectral cut-off (E_(cut) = 117 ^(+18)_(−14) keV), and to place constraints on the Comptonization parameters of the primary continuum for the first time. The hard over soft compactness is 69 ^(+124)_(−24) and the optical depth is 4. 1 ^(+0. 5)_(−3. 6), his leads to an electron temperature of 30 ^(+32)_(−8) keV. Expanding our study of the Comptonization spectrum to the optical/UV by studying the simultaneous Swift-UVOT data, we find indications that the compactness of the corona allows only a small fraction of the total UV/optical flux to be Comptonized. Our analysis of the reprocessed emission show that 3C 390. 3 only has a small amount of reflection (R ∼ 0. 3), and of that the vast majority is from distant neutral matter. However, we also discover a soft-X-ray excess in the source, which can be described by a weak ionized reflection component from the inner parts of the accretion disk. In addition to the backscattered emission, we also detect the highly ionized iron emission lines Fe xxv and Fe xxvi.
[ "Universe Sciences", "Fundamental Constituents of Matter" ]
10.1016/j.it.2018.02.004
Cutaneous Barriers and Skin Immunity: Differentiating A Connected Network
The skin is the outermost barrier of the organism that ensures protection from external harm. Lately, our view of the skin has evolved from an inert mechanical barrier to an active organ that can sense danger signals and mount perfectly adapted defense measures in response to invading pathogens. This Review highlights the different levels of the cutaneous barrier (the microbiome, chemical, physical, and immune barriers), their characteristics, and functional, highly interconnected network of cells and mediators that allow balanced defense measures to protect the body and maintain barrier integrity.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Immunity, Infection and Immunotherapy" ]
865230
A Single-Photon Source Featuring Unity Efficiency And Unity Indistinguishability For Scalable Optical Quantum Information Processing
Within optical quantum information processing, the quantum bits are encoded on single photons and their quantum mechanical properties are exploited to build new functionality. A prime example is the quantum computer, which can be built simply from single-photon sources and detectors, and simple optical components. However for scalable optical quantum computing involving hundreds of photons, the performance requirements for the single-photon source are daunting: the source must feature near-unity efficiency and near-unity indistinguishability simultaneously! Today, all known source designs suffer from inherent trade-offs between efficiency and indistinguishability and their performance is insufficient for scalable quantum computing. The project objective is to realize a source of single indistinguishable photons with performance of ground-breaking nature. The break-through lies in the simultaneous realization of near-unity efficiency and indistinguishability, a combination which overcomes the limitations of present state-of-the-art and ventures far into the regime of scalable quantum computing. As an expert in single-photon source engineering I find myself in a unique position to address this challenge. Since it is unknown how to design such a source, I will first establish a new understanding of the physics of the near-unity regime, where phonon-induced decoherence represents a main limitation for the indistinguishability. I will then advance state-of-the-art in optical engineering by proposing a novel design, where all physical parameters can be controlled independently. The modelling of the near-unity performance source is extremely demanding, and the analysis requires additional advances within optical simulations and open quantum systems theory. Once this is achieved, I will fabricate a prototype and test it in a multi-photon interference boson sampling experiment to unambiguously prove that scalable optical quantum information processing is indeed within reach.
[ "Fundamental Constituents of Matter", "Systems and Communication Engineering" ]
10.1021/acsnano.5b02762
Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs
Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus. (Figure Presented).
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases", "Materials Engineering" ]
10.1038/s41434-020-0175-3
Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering
The low gene manipulation efficiency of human hematopoietic stem and progenitor cells (HSPC) remains a major hurdle for sustainable and broad clinical application of innovative therapies for a wide range of disorders. Given that all current and emerging gene transfer and editing technologies are bound to expose HSPC to exogenous nucleic acids and most often also to viral vectors, we reason that host antiviral factors and nucleic acid sensors play a pivotal role in the efficacy of HSPC genetic manipulation. Here, we review recent progress in our understanding of vector–host interactions and innate immunity in HSPC upon gene engineering and discuss how dissecting this crosstalk can guide the development of more stealth and efficient gene therapy approaches in the future.
[ "Immunity, Infection and Immunotherapy", "Integrative Biology: from Genes and Genomes to Systems", "Cell Biology, Development, Stem Cells and Regeneration", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1007/s00440-014-0550-3
Large deviations for occupation time profiles of random interlacements
We derive a large deviation principle for the density profile of occupation times of random interlacements at a fixed level in a large box of (formula Presented). As an application, we analyze the asymptotic behavior of the probability that atypically high values of the density profile insulate a macroscopic body in a large box. As a step in this program, we obtain a similar large deviation principle for the occupation-time measure of Brownian interlacements at a fixed level in a large box of (formula Presented), and we derive a new identity for the Laplace transform of the occupation-time measure, which is based on the analysis of certain Schrödinger semi-groups.
[ "Mathematics" ]
Q2701905
sostegno al mantenimento delle microimprese e delle piccole imprese colpite dall'epidemia di COVID-19 in una situazione di improvvisa carenza o mancanza di liquidità
Il progetto riguarda il sostegno al capitale circolante di una società in caso di diminuzione del fatturato (entrate derivanti dalle vendite) causata dagli effetti negativi dell'epidemia di COVID-19.
[ "Individuals, Markets and Organisations" ]
10.1038/s41467-018-05077-9
Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts
Interaction of T cell with antigen-bearing dendritic cells (DC) results in T cell activation, but whether this interaction has physiological consequences on DC function is largely unexplored. Here we show that when antigen-bearing DCs contact T cells, DCs initiate anti-pathogenic programs. Signals of this interaction are transmitted from the T cell to the DC, through extracellular vesicles (EV) that contain genomic and mitochondrial DNA, to induce antiviral responses via the cGAS/STING cytosolic DNA-sensing pathway and expression of IRF3-dependent interferon regulated genes. Moreover, EV-treated DCs are more resistant to subsequent viral infections. In summary, our results show that T cells prime DCs through the transfer of exosomal DNA, supporting a specific role for antigen-dependent contacts in conferring protection to DCs against pathogen infection. The reciprocal communication between innate and adaptive immune cells thus allow efficacious responses to unknown threats.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
202499
Experimental Linear Optics Quantum Information Processing with Atoms and Photons
Quantum information science and atom optics are among the most active fields in modern physics. In recent years, many theoretical efforts have been made to combine these two fields. Recent experimental progresses have shown the in-principle possibility to perform scalable quantum information processing (QIP) with linear optics and atomic ensembles. The main purpose of the present project is to use atomic qubits as quantum memory and exploit photonic qubits for information transfer and processing to achieve efficient linear optics QIP. On the one hand, utilizing the interaction between laser pulses and atomic ensembles we will experimentally investigate the potentials of atomic ensembles in the gas phase to build quantum repeaters for long-distance quantum communication, that is, to develop a new technological solution for quantum repeaters making use of the effective qubit-type entanglement of two cold atomic ensembles by a projective measurement of individual photons by spontaneous Raman processes. On this basis, we will further investigate the advantages of cold atoms in an optical trap to enhance the coherence time of atomic qubits beyond the threshold for scalable realization of quantum repeaters. Moreover, building on our long experience in research on multi-photon entanglement, we also plan to perform a number of significant experiments in the field of QIP with particular emphasis on fault-tolerant quantum computation, photon-loss-tolerant quantum computation and cluster-state based quantum simulation. Finally, by combining the techniques developed in the above quantum memory and multi-photon interference experiments, we will further experimentally investigate the possibility to achieve quantum teleportation between photonic and atomic qubits, quantum teleportation between remote atomic qubits and efficient entanglement generation via classical feed-forward. The techniques that will be developed in the present project will lay the basis for future large scale
[ "Fundamental Constituents of Matter", "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.2514/1.60701
Mean Orbital Elements Estimation For Autonomous Satellite Guidance And Orbit Control
Satellite guidance and orbit control often use mean elements as inputs. Whereas traditional missions can use ground-station-based calculation of mean elements, this is not possible in autonomous satellites, which are required to perform onboard estimation of the mean elements. This problem is not trivial, because analytical satellite theories are not robust to modeling errors and cannot easily accommodate thrust. The purpose of this paper is to develop an effective filtering algorithm for onboard estimation of the mean orbital elements in small-eccentricity low Earth orbits. To that end, a semianalytical astrodynamical model that includes zonal/tesseral/sectorial harmonics and drag is formulated to capture the daily, long-periodic, and secular evolution of the mean orbital elements. The mapping from mean to osculating elements is used as a measurement equation by adding the short-periodic terms. This unique formulation is then fed into a spherical-simplex square-root unscented Kalman filter, which serves . . .
[ "Systems and Communication Engineering", "Universe Sciences" ]
10.1681/ASN.2014090875
Combined Deletion Of Vhl And Kif3A Accelerates Renal Cyst Formation
A subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium-specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography-based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
W4297399803
Tendencias en la mortalidad por cáncer de pulmón en Colombia, 1985-2018
To determine lung cancer mortality trends in Colombia during the period 1985-2018 in the population aged 35 years and over and identify changes in the trend.Analysis of mortality time series. The specific standardized rates by sex and age group were calculated. Using joinpoint regression, the annual percentage change in the rates was estimated and points of change were identified.During the period 1985-2018, 105 553 deaths from lung cancer were reported in the population aged 35 and over. The standardized rates exhibit a downward trend during the period 1985-2005, except in people over the age of 64.Lung cancer death rates in Colombia are trending downward. Primary and secondary prevention measures with respect to tobacco use need to be enhanced and other risk factors, such as residential radon or occupation, monitored.Determinar a evolução da mortalidade por câncer de pulmão na Colômbia no período de 1985 a 2018, na população com 35 anos de idade ou mais, e identificar mudanças na tendência.Análise de séries temporais de mortalidade. Foram calculadas taxas específicas e padronizadas por sexo e faixa etária. Por meio da regressão joinpoint, estimou-se o percentual de variação anual das taxas e foram identificados os pontos de variação.No período de 1985 a 2018, foram registradas 105.553 mortes por câncer de pulmão na população com 35 anos de idade ou mais. As taxas padronizadas demonstram tendência decrescente no período de 1985 a 2005, exceto para maiores de 64 anos.A tendência das taxas de mortalidade por câncer de pulmão na Colômbia é descendente. É necessário promover medidas de prevenção primária e secundária acerca do consumo de tabaco e monitorar outros fatores de risco, como a exposição ao radônio residencial ou a ocupação.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physiology in Health, Disease and Ageing" ]
10.1051/0004-6361/201730645
The Flying Saucer Tomography Of The Thermal And Density Gas Structure Of An Edge On Protoplanetary Disk
Context. Determining the gas density and temperature structures of protoplanetary disks is a fundamental task in order to constrain planet formation theories. This is a challenging procedure and most determinations are based on model-dependent assumptions. Aims. We attempt a direct determination of the radial and vertical temperature structure of the Flying Saucer disk, thanks to its favorable inclination of 90 degrees. Methods. We present a method based on the tomographic study of an edge-on disk. Using ALMA, we observe at 0. 5″ resolution the Flying Saucer in CO J = 2–1 and CS J = 5–4. This edge-on disk appears in silhouette against the CO J = 2–1 emission from background molecular clouds in ρ Oph. The combination of velocity gradients due to the Keplerian rotation of the disk and intensity variations in the CO background as a function of velocity provide a direct measure of the gas temperature as a function of radius and height above the disk mid-plane. Results. The overall thermal structure is consistent with model predictions, with a cold (<12−15 K) CO-depleted mid-plane and a warmer disk atmosphere. However, we find evidence for CO gas along the mid-plane beyond a radius of about 200 au, coincident with a change of grain properties. Such behavior is expected in the case of efficient rise of UV penetration re-heating the disk and thus allowing CO thermal desorption or favoring direct CO photo-desorption. CO is also detected at up to 3–4 scale heights, while CS is confined to around 1 scale height above the mid-plane. The limits of the method due to finite spatial and spectral resolutions are also discussed. Conclusions. This method appears to be a very promising way to determine the gas structure of planet-forming disks, provided that the molecular data have an angular resolution which is high enough, on the order of 0. 3−0. 1″ at the distance of the nearest star-forming regions.
[ "Universe Sciences", "Physical and Analytical Chemical Sciences" ]
948371
Beliefs and Gender Inequality
There are large differences in earnings between men and women. Recent work highlights the importance of parenthood for the existence of gender inequality in the labour market. Estimates of the long-run ‘child penalty’, i.e. the impact of having children on women’s relative to men’s earnings, are large and vary substantially across countries. Neither the existence of child penalties nor the striking cross-country variation in child penalties is well understood. BELIEFS will collect a representative dataset of 80,000 individuals in the 28 EU Member States to study the role of several factors in explaining the cross-country differences in child penalties. It will examine the role of (i) beliefs about the benefits/costs to fertility and labour supply decisions, (ii) preferences for having children and for work/leisure, (iii) constraints, and (iv) social norms. BELIEFS will explore different dimensions of heterogeneity and study the individual-level (gender, age etc.) and country-level (labour regulations, family policies etc.) determinants of these factors. It will study whether there are misperceptions of norms and identify whether informing individuals of prevalent social norms shifts their beliefs about the benefits/costs to men/women working and their support for public policies. BELIEFS examines educational, fertility and labour supply decisions in a dynamic life-cycle framework and explores the role of beliefs, preferences, constraints and norms in those decisions. The dynamic framework will also be used to study the role of perceived child penalties in explaining fertility and educational choices. The project is highly ambitious in its scope and it is highly innovative in its combination of research methods. Ultimately, this research agenda will shed light on what drives gender gaps in labour market outcomes as well as which policies may be effective in narrowing these gaps.
[ "The Social World and Its Interactions", "Individuals, Markets and Organisations" ]
US 7900464 W
METHOD AND SYSTEM FOR SUBSCRIPTION TELEVISION BILLING AND ACCESS
A subscription television system and method in which billing information regarding programs actually viewed by a subscriber of the system is accumulated (20) over nondedicated telephone lines. A scrambled television program signal containing a block of television program material (14), a program identification code (18) unique to the block of program material, and a program category code (18), is broadcast (16). The codes are preferably included in the vertical retrace interval of the video portion of the program signal and the transmitted program signal is selectively received at a subscriber station (12) and selectively unscrambled (24) to permit viewing of the block of program material being transmitted in response to subscriber action (30) indicating acceptance for viewing of the block of program material. The received program category code is compared (92) with a locally generated category code (90) to determine whether the program is acceptable for viewing. The program identification code is detected (64) and stored (68) for subsequent transmission in response to the subscriber action indicating acceptance for viewing of the received block of program material. The program identification code stored at the subscriber station is selectively accessed from a remote location (10) over telephone lines on other than a real time basis (e.g., a periodic basis) to thereby provide billing information at the remote location as to programs actually viewed by the subscriber. The subscriber can thus be billed monthly or on some desired periodic basis for programs actually viewed during the preceding period. The billing period can be varied (32, 70) from the remote location (10) to provide a means to control the number of programs which a subscriber can receive.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
W2001820906
Feasibility Study of Fe-ti based Oxygen Carriers for Chemical Looping Combustion
Abstract The reactivity and high fuel conversion efficiency of metal oxide as oxygen carrier are two of the most important functions that can be research in order to make chemical looping combustion (CLC) a reality. In this study, oxygen carriers of Fe 2 O 3 , supported by titanium oxides were prepared to evaluate the feasibility as oxygen carriers for chemical looping by thermogravimetric analyzer (TGA), as well as gas conversion in a fixed bed reactor (FBR). Supported Fe 2 O 3 oxygen carriers and sintered in air at 1100C is a suitable preparation parameter to demonstrate reasonable oxygen conversion. The reduction mechanism of supported Fe 2 O 3 oxygen carriers were proposed in accordance with TGA and x-ray diffraction analysis (XRD) characterizations. Fe 2 TiO 5 and inherent TiO 2 as supporting material would be formed and carried on FBR in practical operation. The preparation of FT-03 (80% Fe 2 O 3 and 20% TiO 2 ) oxygen carrier demonstrated high CO 2 yields regarding to syngas (10% H 2 and 10% CO in N 2 ) and methane (10% CH 4 in N 2 ) combustion in FBR, operated at temperatures higher than 500 and 900C, respectively. Moreover, great mechanical strength and reasonable reactivity of supported Fe 2 O 3 oxygen carriers were also examined by texture analyzer with well-suited for used in CLC.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Products and Processes Engineering", "Materials Engineering" ]
W4280521333
Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project)
To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.Evaluator blinded, randomised controlled trial.16 clinical sites across 11 European countries, January 2016 to 31 October 2019.1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes.Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34).A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.ClinicalTrials.gov NCT02582138.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
EP 05003282 A
Extruded product
An extruded product formed by extrusion molding and continuing in a longitudinal direction includes: an extruded product body (51); and a decoration layer (57) provided integrally on a surface of the extruded product body, wherein the decoration layer is provided on a substantially entire surface of the decoration layer by combining an irregular surface pattern (57c) and a plurality of linear grooves (57b) on the surface thereof, and the depth of the linear groove (57b) is deeper than the depth of the irregular surface pattern (57c). <IMAGE> <IMAGE>
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1080/00220388.2015.1028536
Distributive Politics And Regional Development Assessing The Territorial Distribution Of Turkey S Public Investment
Turkey is often perceived as a country with low bureaucratic capacity and prone to political manipulation and ‘pork-barrel’. This article tests whether this is the case, by analysing the extent to which politics, rather than equity and efficiency criteria, have determined the geographical allocation of public investment across the 81 provinces of Turkey between 2005 and 2012. The results show that although the Turkish government has indeed channelled public expenditures to reward its core constituencies, socioeconomic factors remained the most relevant predictors of investment. Moreover, in contrast to official regional development policy principles, we uncover the concentration of public investment in areas with comparatively higher levels of development. We interpret this as the state bureaucracy’s intentional strategy of focussing on efficiency by concentrating resources on ‘the better off among the most in need’.
[ "Human Mobility, Environment, and Space", "Individuals, Markets and Organisations" ]
10.1021/acs.cgd.6b01468
A gold complex single crystal comprising nanoporosity and curved surfaces
Complex hierarchical shapes are widely known in biogenic single crystals, but growth of intricate synthetic metal single crystals is still a challenge. Here we report a simple method for growing intricately shaped single crystals of gold, each consisting of a micron-sized crystal surrounded by a nanoporous structure, while the two parts constitute a single crystal. This is achieved by annealing thin films of gold and germanium to solidify a eutectic composition melt at a hypoeutectic concentration (Au-enriched composition). Transmission electron microscopy and synchrotron submicron scanning diffractometry as well as imaging confirmed that the whole structure was indeed a single crystal. A kinetic model showing how this intricate single-crystal structure can be grown is presented.
[ "Condensed Matter Physics", "Materials Engineering" ]
624162
Traceability at wine industry through integrated labelling of typicality, health protection effect and organoleptic attributes
The wine market has changed dramatically in the last fifty years, moving from small national markets, scarcely spread and limited to specialists, to the globalized web revolution. Wine industry represents an important part of both agriculture and food industry in many countries (i.e ES, FR and IT represent alone a total of 32% of world vineyard surface area, being within top 5 world producers of grapes in 2018). However, wine industry is threatened by counterfeit products and illicit trades. The overall research and technology development goal of TRACEWINDU is to improve productivity of vineyards by using novel combination of Plant Protection Products while simultaneously geographic origin analysis is integrated in a multi-approach strategy to ensure wine traceability/authentication. Such approach will be correlated with the obtained outputs of sensory analysis to generate a labelling score chart data in form of product passport included in smart tags. The smart tag are physical labels with unique item-level identifiers in form of QR codes for digital and dynamic information sharing and provisioning of all relevant product information throughout product’s lifecycle, and transparency of product data facilitating decentralized blockchain technology. Through implemented smart tags, TRACEWINDU supports tracing bottles back directly to producer and each time a bottle changes hands, the origin is updated, and ownership is transferred, and those bottles certified at the time and place of production, by producers will carry even more value in secondary markets. Overall, TRACEWINDU aims to foster, improve and develop permanent international and inter-sector collaboration between academic research centers and private sector, enhancing the exchange of knowledge, best practices, know-how, innovations, experience, mutual cooperation and culture of work at different regions and countries (ES, FR, IT, ME, RS, AR) through a series of scheduled secondments.
[ "Products and Processes Engineering", "Computer Science and Informatics", "Systems and Communication Engineering", "Physical and Analytical Chemical Sciences" ]
W1944979283
New horizons for cutaneous microbiology: the role of biofilms in dermatological disease
Human skin is colonized by bacteria. The development of new genomic microbiological techniques has revealed that the bacterial ecology of human skin is far more complex than previously imagined and includes many fastidious or noncultivable bacterial species which are found on both normal and diseased skin. In nature, the predominant bacterial phenotype on epithelial surfaces is that of organisms organized within a biofilm. This contrasts with the widely held belief that bacteria are planktonic, i.e. free-floating single cells. Biofilms are sessile bacterial communities encased in an extracellular matrix that have a well-developed communication system and can regulate bacterial growth and metabolism, confer resistance to antimicrobials and to host inflammatory cells, and alter host metabolism. Biofilms have been observed on healthy skin and in a number of dermatological conditions, including some that were previously thought not to have an infectious aetiology. Here we review the concept of biofilms and their role in cutaneous health and disease.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Immunity, Infection and Immunotherapy", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1063/1.4812461
Predicting Phase Behavior In Multicomponent Mixtures
Mixtures with a large number of components can undergo phase transitions of a hybrid character, with both condensation and demixing contributions. We describe a robust Monte Carlo simulation method for calculating phase coexistence in multicomponent mixtures. We use this approach to study the phase behavior of lattice models of multicomponent mixtures with strongly varying pair interactions. Such a system can be thought of as a simplified model of the cytosol, with both specific and nonspecific interactions. We show that mapping a multicomponent mixture onto an approximately equivalent one-component system yields both upper and lower bounds on the maximum solute volume fraction of a stable, homogeneous phase. By following the minimum excess-free-energy path from the dilute phase free-energy minimum, we predict the difference in composition between the condensed and dilute phases at the boundary of the homogeneous phase. We find that this “direction” of phase separation rarely aligns with the dominant direction of density fluctuations in the dilute phase. We also show that demixing transitions tend to lower the maximum solute volume fraction at which the homogeneous phase is stable. By considering statistical ensembles of mixtures with random interactions, we show that the demixing contribution to phase separation is self-averaging and dependent only on the mean and variance of the distribution of interactions.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1016/j.geb.2014.03.007
A folk theorem for stochastic games with private almost-perfect monitoring
We prove a folk theorem for stochastic games with private, almost-perfect monitoring and observable states when the limit set of feasible and individually rational payoffs is independent of the state. This asymptotic state independence holds, for example, for irreducible stochastic games. Our result establishes that the sophisticated construction of Hörner and Olszewski (2006) for repeated games can be adapted to stochastic games, reinforcing our conviction that much knowledge and intuition about repeated games carries over to the analysis of irreducible stochastic games.
[ "Mathematics", "Computer Science and Informatics" ]
interreg_2612
Promoting Accessible and Sustainable Tourism for Future
The Project tackles the main common challenges of the programme internal and rural areas: creating new tourist destinations through  promotion of natural and cultural heritage; supporting diversification, customization, integration and specialization of local tourist services by focusing on accessibility and sustainability; improving common knowledge of new trends in the tourism market and the marketing capacity of SME and local communities to promote a tourism based on the experience of “new communities”; providing smart systems capable of promoting the best international tourist marketing . Therefore the project&#39;s objective is to promote and strengthen the Accessible and Sustainable tourism offer of the cross border area at a European and international level, through the implementation and diversification of the tourist products/services in the target areas. It will implement  a new Cross border Accessible and Sustainable Community Tourist Destination, able to increase the tourists incoming (in particular people with special needs) and consequentially the promotion of the natural, environmental, historical and cultural heritage, boosting a smart and sustainable economic development in the whole Cross border area. This will lead to turn Accessible and Sustainable tourism into the development flywheel of the cross border internal/rural areas. The main outputs of the Project are the 1) Cross border Network for A&S Tourism, 2) the Cross border Destination Management Organization for A&S Tourism, 3) Web platform and APP, 4) Valorized sites for tourits and especially for people with special needs. The local rural communities (public authorities, SME, NGO, citizens) will benefit from them. The project’s approach is based on Community-Led Local Development, focused on specific sub-regional areas&#39; needs and assets, aiming to create local hospitality systems by opening rural communities towards new tourist inflows in a cross border framework.
[ "Human Mobility, Environment, and Space", "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
interreg_1705
Interregional Hospital Network for Energy Sustainability
The healthcare industry belongs to the most energy intensive sectors in Europe. 6.000 kWh electricity and 29.000 kWh heat per year and bed (Viamedica (2009): “Klinergie 2020”) are consumed. That energy consumption equals two modern single-family houses. Apart from a 24/7 heating or cooling demand there are additional energy needs for sterilization, lightning, electronic infrastructure and other medical equipment of course. According to recent studies and already realized projects it is possible to reduce the electrical consumption by up to 40% and to decrease the thermal energy demand by at least 30%. Different climate and legal conditions as well as different focus in regard to health care lead to different requirement profiles from an energy perspective. Based on a common Energy Performance Indicator System the effectiveness of energy efficiency measures shall be validated and thus ease replication efforts. In order to promote energy efficiency and energy management in the health sector, a transnational network of hospital operators, research institutes and engineering offices is created. Based on shared energy indicators, building characteristics and energy management processes are compared, going to define specific efficiency measures to be applied transversally to the project partners. A software tool for the evaluation and planning of specific measures will be developed within the project.
[ "Products and Processes Engineering", "Earth System Science" ]
10.1016/j.molmed.2016.07.001
MicroRNA Regulators of Anxiety and Metabolic Disorders
Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulatory networks in metabolic and anxiety-related conditions. In particular, miRNAs involved in these disorders include regulators of acetylcholine signaling in the nervous system and their accompanying molecular machinery. These have been associated with anxiety-prone states in individuals, while also acting as inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead to dysregulated metabolism. Common pathways in metabolic and anxiety-related phenomena might offer an opportunity to reclassify ‘healthy’ and ‘unhealthy’, as well as metabolic and anxiety-prone biological states, and inform putative strategies to treat these disorders.
[ "Neuroscience and Disorders of the Nervous System", "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2746002251
Sustainable economic governance: learning from Kautilya's Arthashastra
Sustainable economic governance requires effectual rules and policies and their effective implementation. Arthashastra written by Kautilya more than two thousand years ago discusses various best practices on governance of markets, economics and trade to ensure happiness and wellbeing of the subjects. Most of the wisdom of Arthashastra are still relevant and are being adopted knowingly or knowingly by present day governments. This paper discusses the teachings of Arthashastra on critical economic policy areas and their key elements and tries to relate its application with present day scenario. The paper discusses how Arthashastra lessons on public finance, trade, taxation and administration have been or can be incorporated in Indian context to achieve the ultimate objective of sustainable economic governance. The paper further combines the key teachings on economic governance and presents a model which can act as a guide for good economic governance.
[ "Institutions, Governance and Legal Systems", "Individuals, Markets and Organisations" ]
W244217642
Abstract 12088: cMyBP-C’S Interaction With Actin is Critical to Maintain Diastolic Function in vivo
Background: cMyBPC’s interaction with actin is critical to maintain diastolic function in vivo Rationale: Extensive studies demonstrate that cardiac myosin binding protein C (cMyBP-C) is a critical mediator of diastolic function through its interaction with actin, myosin and titin. The precise molecular mechanisms underlying the protein’s function remain elusive as cMyBP-C’s structural domains responsible for actin and/or myosin interaction are ill-defined and the physiological consequences of these filament interactions are unknown. Objective: In the present study, we made transgenic mice that lacked cMyBP-C’s actin and/or the head region of the myosin heavy chain (S2-MyHC) sites in order to better understand the molecular mechanisms of cMyBPC-mediated regulation of cardiac contraction, particularly diastolic function. Methods and Results: Using a combination of genetics and functional assays, we defined cMyBP-C’s N-terminal structural domains as well as the critical residues necessary or sufficient to mediate interactions with actin and/or S2-MyHC. Using genetic experiments, we first confirmed that mutation of three lysines to alanines in the C1 domain abolished actin binding (cMyBP-C Act- ). Similarly, mutation of three arginines to alanines in the “m” domain abolished S2-MyHC binding (cMyBP-C S2- ). To determine the functional roles of these sites in vivo, we generated transgenic lines in which normal cMyBP-C was replaced by either cMyBP-C Act-,S2- or wild type (cMyBP-C WT ), transgenically-encoded cMyBP-C. Mutant protein was completely substituted for endogenous cMyBP-C by breeding the transgenes into a cMyBP-C null background. The cMyBP-C Act-,S2- mice developed significant cardiac hypertrophy with myofibrillar disarray and fibrosis. Echocardiographic Doppler measurements showed that cMyBP-C Act-,S2- mice develop both diastolic and systolic dysfunction. In contrast, the cMyBP-C WT Tg line showed normal cardiac structure and function. Conclusions: These results suggest that the cMyBP-C’s interactions with both actin/S2-MyHC are structurally important to preserve normal cardiac contractility and particularly, cMyBP-C’s interaction with actin is indispensable for normal diastolic function.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
616179
Pre-Columbian Amazon-Scale Transformations
The protection of rainforests and the development of sustainable land-use practices in the humid tropics are of global significance because these forests represent a major reservoir of biodiversity and are of crucial importance for the regulation of Earth’s climate. A sound understanding of the historical role of humans in shaping Amazonian landscapes and to what extent Amazonian forests were resilient to historical disturbance is critical to make informed policy decisions about sustainable Amazonian futures. However, the nature and scale of pre-Columbian land use and its modern legacy on Amazonian landscapes are among the most debated topics in New World archaeology, palaeoecology and conservation. To resolve this debate, this project will investigate the influence of the late pre-Columbian (1000-1492 A.D.) land use on Amazonian landscapes, the impact of the 1492 Columbian Encounter (CE) and its modern legacy through the comparative study of pre-Columbian land uses in four different regions of Amazonia. It will apply, for the first time, an innovative interdisciplinary approach that integrates archaeology, ethnohistory, archaeobotany, paleoecology, soil science, landscape ecology and remote sensing (including the novel application of LIDAR survey) to the following study regions: (1) the Santarem Amazonian Dark Earth sites in the Lower Amazon, (2) the interfluvial areas of the Purus-Madeira Rivers in the Central Amazon, (3) the Acre geoglyphs of SW Amazonia and (4) the ring-ditches of the Baures forested areas of the Bolivian Amazon. The results of the project have broader implications not only for archaeology and geography but for conservation and sustainable Amazonian futures.
[ "Earth System Science", "The Study of the Human Past", "Environmental Biology, Ecology and Evolution" ]
10.1007/978-3-030-00934-2_25
A Probabilistic Model Combining Deep Learning And Multi Atlas Segmentation For Semi Automated Labelling Of Histology
Thanks to their high resolution and contrast enhanced by different stains, histological images are becoming increasingly widespread in atlas construction. Building atlases with histology requires manual delineation of a set of regions of interest on a large amount of sections. This process is tedious, time-consuming, and rather inefficient due to the high similarity of adjacent sections. Here we propose a probabilistic model for semi-automated segmentation of stacks of histological sections, in which the user manually labels a sparse set of sections (e. g. , one every n), and lets the algorithm complete the segmentation for other sections automatically. The proposed model integrates in a principled manner two families of segmentation techniques that have been very successful in brain imaging: multi-atlas segmentation (MAS) and convolutional neural networks (CNNs). Within this model, we derive a Generalised Expectation Maximisation algorithm to compute the most likely segmentation. Experiments on the Allen dataset show that the model successfully combines the strengths of both techniques (effective label propagation of MAS, and robustness to misregistration of CNNs), and produces significantly more accurate results than using either of them independently.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Computer Science and Informatics" ]
10.3389/fncel.2018.00011
Internal state dependent odor processing and perception—The role of neuromodulation in the fly olfactory system
Animals rely heavily on their sense of olfaction to perform various vital interactions with an ever-in-flux environment. The turbulent and combinatorial nature of air-borne odorant cues demands the employment of various coding strategies, which allow the animal to attune to its internal needs and past or present experiences. Furthermore, these internal needs can be dependent on internal states such as hunger, reproductive state and sickness. Neuromodulation is a key component providing flexibility under such conditions. Understanding the contributions of neuromodulation, such as sensory neuron sensitization and choice bias requires manipulation of neuronal activity on a local and global scale. With Drosophila’s genetic toolset, these manipulations are feasible and even allow a detailed look on the functional role of classical neuromodulators such as dopamine, octopamine and neuropeptides. The past years unraveled various mechanisms adapting chemosensory processing and perception to internal states such as hunger and reproductive state. However, future research should also investigate the mechanisms underlying other internal states including the modulatory influence of endogenous microbiota on Drosophila behavior. Furthermore, sickness induced by pathogenic infection could lead to novel insights as to the neuromodulators of circuits that integrate such a negative postingestive signal within the circuits governing olfactory behavior and learning. The enriched emporium of tools Drosophila provides will help to build a concrete picture of the influence of neuromodulation on olfaction and metabolism, adaptive behavior and our overall understanding of how a brain works.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2483923550
Effects of catchment characteristics and climatic conditions on reservoir water capacity in a drought prone area
Crop production in semi-arid sub-Saharan Africa (SSA) is limited by over-reliance on erratic and inadequate rainfall, which often results in yield reduction or total crop failure. The effects of frequent droughts and dry spells need to be circumvented by water conservation. Where rainwater is harvested, research recommendations are based on direct use of the water without relating it to catchment characteristics, climatic conditions and long term storage. A study aimed at predicting sizes of seasonal open surface reservoir based on rainfall and runoff rainwater was conducted from 2012 to 2013 at Ukwe Area, Malawi. The work premised on assessment of land and hydrological factors as they impinge on runoff water storage. Rainfall-runoff relative analysis showed runoff trend following the magnitude of rainfall. Findings showed that runoff water harvested, under the Ukwe area landscape conditions, is linearly related to seasonal rainfall amount with coefficient of correlation of greater than 0.75, demonstrating vitality of rain and timing of rain harvesting for reservoir sustenance. Runoff amount was almost four times that of infiltrated amount, highlighting the fact that drought prone areas can be flood prone as well. Results further demonstrate that weekly reservoir balance using crop, livestock and domestic consumption, and losses through evaporation and seepage, as dry season progresses are critical for reservoir sizing during dam construction or crop field sizing at the onset of dry season.   Key words: Semi-arid, rainwater, reservoir, Malawi, runoff, coefficient.
[ "Earth System Science", "Products and Processes Engineering" ]
10.1051/0004-6361/201527780
Planck Intermediate Results Xlv Radio Spectra Of Northern Extragalactic Radio Sources
Continuum spectra covering centimetre to submillimetre wavelengths are presented for a northern sample of 104 extragalactic radio sources, mainly active galactic nuclei, based on four-epoch Planck data. The nine Planck frequencies, from 30 to 857 GHz, are complemented by a set of simultaneous ground-based radio observations between 1. 1 and 37 GHz. The single-survey Planck data confirm that the flattest high-frequency radio spectral indices are close to zero, indicating that the original accelerated electron energy spectrum is much harder than commonly thought, with power-law index around 1. 5 instead of the canonical 2. 5. The radio spectra peak at high frequencies and exhibit a variety of shapes. For a small set of low-z sources, we find a spectral upturn at high frequencies, indicating the presence of intrinsic cold dust. Variability can generally be approximated by achromatic variations, while sources with clear signatures of evolving shocks appear to be limited to the strongest outbursts.
[ "Universe Sciences", "Physical and Analytical Chemical Sciences" ]
10.1080/00018732.2016.1211393
Statistical Physics Of Inference Thresholds And Algorithms
Many questions of fundamental interest in today's science can be formulated as inference problems: some partial, or noisy, observations are performed over a set of variables and the goal is to recover, or infer, the values of the variables based on the indirect information contained in the measurements. For such problems, the central scientific questions are: Under what conditions is the information contained in the measurements sufficient for a satisfactory inference to be possible? What are the most efficient algorithms for this task? A growing body of work has shown that often we can understand and locate these fundamental barriers by thinking of them as phase transitions in the sense of statistical physics. Moreover, it turned out that we can use the gained physical insight to develop new promising algorithms. The connection between inference and statistical physics is currently witnessing an impressive renaissance and we review here the current state-of-the-art, with a pedagogical focus on the Ising . . .
[ "Mathematics", "Computer Science and Informatics" ]
10.1080/17550874.2019.1626509
Perspectives For Ecological Networks In Plant Ecology
ABSTRACTBackground: Plant communities are usually characterised by species composition and abundance, but also underlie a multitude of complex interactions that we have only recently started unveil. . .
[ "Environmental Biology, Ecology and Evolution" ]
W4307930540
Fluorose Dentária em Escolares aos 12 anos de Idade, no município de Lauro de Freitas, na Região Metropolitana de Salvador, Bahia, Brasil
A adição de flúor na água de abastecimento público e o heterocontrole têm sido consideradas medidas de promoção da saúde bucal e de prevenção da cárie dentária em diversos países, contudo devem ser acompanhadas da vigilância em saúde da prevalência e severidade da fluorose dentária e da cárie dentária. Neste âmbito, esta pesquisa almeja investigar a prevalência e a severidade da fluorose dentária em escolares residentes no município de Lauro de Freitas, na Região Metropolitana de Salvador (RMS), Bahia, Brasil. Adotou-se uma abordagem metodológica que abrangeu o estudo transversal da prevalência e severidade da fluorose dentária de 680 escolares aos 12 anos de idade (Índice de Dean) no município de Lauro de Freitas. Obteve-se uma proporção da prevalência da fluorose dentária de 34%, com 32,5% dos casos distribuídos nos graus muito leve a leve e 1,5% dos casos diagnosticados pertenceram ao grau moderado de severidade. Este perfil da fluorose foi considerado similar ao perfil observado em estudos anteriores na RMS, ou de áreas não endêmicas de fluorose, sendo, ademais, compatível ao uso de um nível seguro do fluoreto na água de abastecimento público. Demanda-se pela efetividade da vigilância em saúde da fluorose dentária e a formação de profissionais que compreendam o ambiente em suas relações com a saúde e com a sociedade.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Environmental Biology, Ecology and Evolution" ]
10.1016/j.na.2019.01.028
A variational principle for three-dimensional water waves over Beltrami flows
We consider steady three-dimensional gravity–capillary water waves with vorticity propagating on water of finite depth. We prove a variational principle for doubly periodic waves with relative velocities given by Beltrami vector fields, under general assumptions on the wave profile.
[ "Mathematics", "Condensed Matter Physics" ]
10.1016/j.jmb.2016.09.011
Structural Insights into the Inhibitory Mechanism of an Antibody against B7-H6, a Stress-Induced Cellular Ligand for the Natural Killer Cell Receptor NKp30
Antibodies have been shown to block signaling through cell surface receptors using several mechanisms. The two most common are binding to the ligand-binding site of the receptor and, conversely, binding to the receptor-binding site of the ligand. Here, we investigated the inhibitory mechanism of an antibody (17B1. 3) against human B7-H6, a stress-induced cellular ligand for the natural killer (NK) cell receptor NKp30. Binding of this antibody to B7-H6, a transmembrane protein expressed on tumor and other stressed cells, but not on normal cells, prevents NK cell activation via NKp30. We determined the crystal structure of antibody 17B1. 3 in complex with the ectodomain of B7-H6 to 2. 5 Å resolution. Surprisingly, 17B1. 3 binds to a site on B7-H6 that is completely distinct from the binding site for NKp30, such that 17B1. 3 does not block the NKp30–B7-H6 interaction. We then asked whether 17B1. 3 prevents signaling by binding to a putative site for B7-H6 dimerization. However, structure-based mutations designed to disrupt potential B7-H6 dimerization through this site did not diminish NKp30-mediated cell activation. We conclude that the bulky 17B1. 3 antibody most likely acts by sterically interfering with close cell–cell contacts at the NK cell–target cell interface that are required for NK cell activation. A similar inhibitory mechanism may apply to other antibodies, including therapeutic antibodies that block signaling through cell surface receptors whose ligands are also cell surface proteins.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1007/JHEP02(2016)183
Seed Conformal Blocks In 4D Cft
We compute in closed analytical form the minimal set of "seed" conformal blocks associated to the exchange of generic mixed symmetry spinor/tensor operators in an arbitrary representation (l,\bar l) of the Lorentz group in four dimensional conformal field theories. These blocks arise from 4-point functions involving two scalars, one (0,|l-\bar l|) and one (|l-\bar l|,0) spinors or tensors. We directly solve the set of Casimir equations, that can elegantly be written in a compact form for any (l,\bar l), by using an educated ansatz and reducing the problem to an algebraic linear system. Various details on the form of the ansatz have been deduced by using the so called shadow formalism. The complexity of the conformal blocks depends on the value of p=|l-\bar l | and grows with p, in analogy to what happens to scalar conformal blocks in d even space-time dimensions as d increases. These results open the way to bootstrap 4-point functions involving arbitrary spinor/tensor operators in four dimensional conformal field theories.
[ "Mathematics", "Fundamental Constituents of Matter" ]
10.1007/s00381-016-3017-2
Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds
Purpose: In pediatric neurosurgery, decompressive craniectomy and correction of congenital cranial anomalies can result in major cranial defects. Corrective cranioplasty for the repair of these critical-sized defects is not only a cosmetic issue. The limited availability of suitable autogenous bone and the morbidity of donor site harvesting have driven the search for new approaches with biodegradable and bioactive materials. This study aimed to assess the healing of rabbit calvarial critical-sized defects filled with osteogenic material, either with bioactive glass scaffolds or tricalcium phosphate granules in various combinations with adipose stem cells or bone marrow stem cells, BMP-2, BMP-7, or VEGF to enhance osteogenesis. Methods: Eighty-two bicortical full thickness critical-sized calvarial defects were operated. Five defects were left empty as negative control defects. The remaining 77 defects were filled with solid bioactive glass scaffolds or tricalcium phosphate granules seeded with adipose or bone marrow derived stem cells in combination with BMP-2, BMP-7, or VEGF. The defects were allowed to heal for 6 weeks before histologic and micro-CT analyses. Results: Micro-CT examination at the 6-week post-operative time point revealed that defects filled with stem cell-seeded tricalcium phosphate granules resulted in new bone formation of 6. 0 %, whereas defects with bioactive glass scaffolds with stem cells showed new bone formation of 0. 5 to 1. 7 %, depending on the growth factor used. Conclusions: This study suggests that tricalcium phosphate granules combined with stem cells have osteogenic potential superior to solid bioactive glass scaffolds with stem cells and growth factors.
[ "Materials Engineering", "Cell Biology, Development, Stem Cells and Regeneration", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1080/13698230.2019.1610843
Arendt And Political Realism Towards A Realist Account Of Political Judgement
This article argues that Hannah Arendt’s thought can offer significant insights on political judgement for realism in political theory. We identify a realist position which emphasises the need to a. . .
[ "Texts and Concepts" ]
216574
Synchronicity: delivering an iot enabled digital single market for europe and beyond
SynchroniCity represents the first attempt to deliver a Single Digital City Market for Europe by piloting its foundations at scale in 11 reference zones - 8 European cities & 3 more worldwide cities - connecting 34 partners from 11 countries over 4 continents. Building upon a mature European knowledge base derived from initiatives such as OASC, FIWARE, FIRE, EIP-SCC, and including partners with leading roles in standardization bodies, e.g. ITU, ETSI, IEEE, OMA, IETF, SynchroniCity will deliver a harmonized ecosystem for IoT-enabled smart city solutions where IoT device manufacturers, system integrators and solution providers can innovate and openly compete. With an already emerging foundation, SynchroniCity will establish a reference architecture for the envisioned IoT-enabled city market place with identified interoperability points and interfaces and data models for different verticals. This will include tools for co-creation & integration of legacy platforms & IoT devices for urban services and enablers for data discovery, access and licensing lowering the barriers for participation on the market. SynchroniCity will pilot these foundations in the reference zones together with a set of citizen-centred services in three high-impact areas, showing the value to cities, businesses and citizens involved, linked directly to the global market. With a running start, SynchroniCity will serve as lighthouse initiative to inspire others to join the established ecosystem and contribute to the emerging market place. SynchroniCity takes an inclusive approach to grow the ecosystem by inviting businesses and cities to join through an open call, allowing them to participate on the pioneering market place enabling a second wave of successful pilots. They will strengthen the ecosystem by creating a positive ripple effect throughout Europe, and globally, to establish a momentum and critical mass for a strong European presence in a global digital single market of IoT-enabled solutions.
[ "Computer Science and Informatics", "Systems and Communication Engineering", "Products and Processes Engineering" ]
10.1038/s41556-018-0095-2
Early lineage segregation of multipotent embryonic mammary gland progenitors
The mammary gland is composed of basal cells and luminal cells. It is generally believed that the mammary gland arises from embryonic multipotent progenitors, but it remains unclear when lineage restriction occurs and what mechanisms are responsible for the switch from multipotency to unipotency during its morphogenesis. Here, we perform multicolour lineage tracing and assess the fate of single progenitors, and demonstrate the existence of a developmental switch from multipotency to unipotency during embryonic mammary gland development. Molecular profiling and single cell RNA-seq revealed that embryonic multipotent progenitors express a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in embryonic multipotent progenitors promotes unipotent basal cell fate and was sufficient to reprogram adult luminal cells into basal cells by promoting an intermediate hybrid multipotent-like state. Altogether, this study identifies the timing and the mechanisms mediating early lineage segregation of multipotent progenitors during mammary gland development.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1038/emboj.2010.237
Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders
The function of lysosomes relies on the ability of the lysosomal membrane to fuse with several target membranes in the cell. It is known that in lysosomal storage disorders (LSDs), lysosomal accumulation of several types of substrates is associated with lysosomal dysfunction and impairment of endocytic membrane traffic. By analysing cells from two severe neurodegenerative LSDs, we observed that cholesterol abnormally accumulates in the endolysosomal membrane of LSD cells, thereby reducing the ability of lysosomes to efficiently fuse with endocytic and autophagic vesicles. Furthermore, we discovered that soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs), which are key components of the cellular membrane fusion machinery are aberrantly sequestered in cholesterol-enriched regions of LSD endolysosomal membranes. This abnormal spatial organization locks SNAREs in complexes and impairs their sorting and recycling. Importantly, reducing membrane cholesterol levels in LSD cells restores normal SNARE function and efficient lysosomal fusion. Our results support a model by which cholesterol abnormalities determine lysosomal dysfunction and endocytic traffic jam in LSDs by impairing the membrane fusion machinery, thus suggesting new therapeutic targets for the treatment of these disorders.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W1987951345
Rock magnetic investigation of possible sources of the Bangui magnetic anomaly
The Bangui magnetic anomaly (BMA) is the largest lithospheric magnetic field anomaly on Earth at low latitudes. Previous studies investigated its geological source using constraints from satellite and ground magnetic field measurements, as well as from surface magnetic susceptibility measurements on rocks from the Panafrican Mobile Belt Zone (PMBZ). Here we combine magnetic field data modelling and rock magnetic property measurements (susceptibility and natural remanent magnetization, NRM) on many samples from this PMBZ and the surrounding formations. It reveals that NRM is a significant component of the total magnetization (Mt) of the BMA source, which reaches 4.3 A/m with maximum thicknesses of 38 and 54 km beneath the western and eastern parts of the BMA. Only the isolated and relatively thin banded iron formations and some migmatites show such Mt values. Thus we suggest that the thick BMA source may be composed either by overlapped slices of such metamorphic rocks, or by an iron-rich mafic source, or by a combination of these two geological structures.
[ "Earth System Science", "Condensed Matter Physics" ]
10.1080/13501763.2019.1701066
Domestic Contestation Of The European Union
A constitution will not be enough. It can only set democratic processes in motion, processes into which it will then have to put down roots (…) A European party system will take shape only to the e. . .
[ "Institutions, Governance and Legal Systems" ]
10.1051/0004-6361/201832900
Gaia Data Release 2 Observations Of Solar System Objects
Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations. Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality. Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP). Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ∼ 12 - 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ∼ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects. (Less)
[ "Universe Sciences", "Systems and Communication Engineering" ]
IB 2017055112 W
WEIGHT MATERIAL RECOVERY AND REUSE METHOD FROM DRILLING WASTE
A process for recovering weight material for reuse in drilling fluids from a previously unavailable source of feed stock. The process described herein includes a process of cleaning drilling waste through either low temperature thermal or solvent washing to remove hydrocarbon or water based drilling fluid contamination. The cleaned drilling waste, substantially free of liquids is sifted and the bulk fraction is further treated by employing conventional separation technology to recover a high gravity solids phase while discarding low gravity solids phase as tailings. Additionally, described is a process where the recovered high gravity solids phase can be reused as a high density weight material, or lower cost weight material, either of which is desirable to the drilling of modern oil and gas wells. The process of adding drilling fluid back into the recovered weight material to simplify the process of transporting the weight material into an active drilling fluid system is also described.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1002/bit.25587
Genetically expanded cell-free protein synthesis using endogenous pyrrolysyl orthogonal translation system
Cell-free protein synthesis offers a facile and rapid method for synthesizing, monitoring, analyzing, and purifying proteins from a DNA template. At the same time, genetic code expansion methods are gaining attention due to their ability to site-specifically incorporate unnatural amino acids (UAAs) into proteins via ribosomal translation. These systems are based on the exogenous addition of an orthogonal translation system (OTS), comprising an orthogonal tRNA, and orthogonal aminoacyl tRNA synthetase (aaRS), to the cell-free reaction mixture. However, these components are unstable and their preparation is labor-intensive, hence introducing a major challenge to the system. Here, we report on an approach that significantly reduces the complexity, effort and time needed to express UAA-containing proteins while increasing stability and realizing maximal suppression efficiency. We demonstrate an endogenously introduced orthogonal pair that enables the use of the valuable yet insoluble pyrrolysyl-tRNA synthetase in a cell-free system, thereby expanding the genetic repertoire that can be utilized in vitro and enabling new possibilities for bioengineering. With the high stability and efficiency of our system, we offer an improved and accessible platform for UAA incorporation into proteins.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Biotechnology and Biosystems Engineering" ]
W1529638062
Real-Time Binaural Sound Source Localization Using Sparse Coding and SOM
AbstractThis paper presents a binaural sound source localization method using both a sparse coding and a self-organizing map (SOM) in real-time system. We use the sparse coding for feature extraction to estimate the azimuth of sound source. It is used for decomposing input sound signals into three components such as time, frequency and magnitude. Therefore, although the frequency characteristic of ITD (Interaural Time Difference) is changed by shape of head, we utilized it to estimate the azimuth of the sound source considering the time-frequency features simultaneously. Then we adapted the SOM to estimate the azimuth of sound source which is a type of artificial neural networks. This system is constructed by open-source software, Flowdesigner, which gives us a data-flow oriented developmental environment for efficient real-time system.Keywordsreal-time binaural sound source localizationsparse codingSOMflowdesigner
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1039/C8MO00060C
Untargeted Lipidomic Analysis Of Primary Human Epidermal Melanocytes Acutely And Chronically Exposed To Uv Radiation
Ultraviolet (UV) radiation present in sunlight has been related to harmful effects on skin such as premature aging and skin cancer. In order to study the effects of UV radiation on skin, many investigations have been carried out at transcriptomic and proteomic levels. However, studies on the effects of UV radiation on lipid composition are scarce. In this work, primary cultures of melanocytes were exposed to UV radiation in a similar UVA/UVB ratio to that found in solar light. The UV exposure was carried out twice a week and different endpoints were investigated at 0. 5 (acute exposure), 1. 5 and 3 weeks. As a result, dendrite formation and a progressive reduction in cell viability were observed. Also, cell cycle arrest and a reduced E-cadherin content were detected at 0. 5 and 1. 5 weeks. In the second stage of the study, lipid extracts of melanocytes were analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and subjected to an untargeted lipidomic approach using the ROIMCR chemometric method. Among the most important changes observed under UV irradiation, lipid raft components such as sphingomyelins and GM3 gangliosides as well as other signalling molecules such as phosphatidylinositols decreased progressively with time. These modifications indicated strong effects on important functions such as cell signalling and recognition. In contrast, triacylglycerol species, associated with energy storage, increased progressively, which could be interpreted as a survival mechanism under adverse conditions. Further studies are needed to better understand the functional implications of the changes observed.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Physical and Analytical Chemical Sciences" ]
10.1038/s41598-020-63584-6
Self-similarity of low-frequency earthquakes
Low-frequency earthquakes are a particular class of slow earthquakes that provide a unique source of information on the physical processes along a subduction zone during the preparation of large earthquakes. Despite increasing detection of these events in recent years, their source mechanisms are still poorly characterised, and the relation between their magnitude and size remains controversial. Here, we present the source characterisation of more than 10,000 low-frequency earthquakes that occurred during tremor sequences in 2012–2016 along the Nankai subduction zone in western Shikoku, Japan. We show that the scaling of seismic moment versus corner frequency for these events is compatible with an inverse of the cube law, as widely observed for regular earthquakes. Their radiation, however, appears depleted in high-frequency content when compared to regular earthquakes. The displacement spectrum decays beyond the corner frequency with an omega-cube power law. Our result is consistent with shear rupture as the source mechanism for low-frequency earthquakes, and suggests a self-similar rupture process and constant stress drop. When investigating the dependence of the stress drop value on the rupture speed, we found that low-frequency earthquakes might propagate at lower rupture velocity than regular earthquakes, releasing smaller stress drop.
[ "Earth System Science", "Condensed Matter Physics" ]
10.1039/C5GC00712G
The Magic Of Aqueous Solutions Of Ionic Liquids Ionic Liquids As A Powerful Class Of Catanionic Hydrotropes
Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are widely used in the formulation of drugs, cleaning and personal care products. In this work, it is shown that ionic liquids are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the solubility of biomolecules in water. The effects of the ionic liquid chemical structures, their concentration and the temperature on the solubility of two model biomolecules, vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The solubility of these two biomolecules was studied in the entire composition range, from pure water to pure ionic liquids, and an increase in the solubility of up to 40-fold was observed, confirming the potential of ionic liquids to act as hydrotropes. Using dynamic light scattering, NMR and molecular dynamics simulations, it was possible to infer that the enhanced solubility of the biomolecule in the IL aqueous solutions is related to the formation of ionic-liquid–biomolecules aggregates. Finally, it was demonstrated that hydrotropy induced by ionic liquids can be used to recover solutes from aqueous media by precipitation, simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liquid aqueous solutions in the extraction of value-added compounds from biomass as well as in the design of novel processes for their recovery from aqueous media.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Products and Processes Engineering" ]
10.1093/molbev/mss326
Origins of shared genetic variation in African cichlids
Cichlid fishes have evolved tremendous morphological and behavioral diversity in the waters of East Africa. Within each of the Great Lakes Tanganyika, Malawi, and Victoria, the phenomena of hybridization and retention of ancestral polymorphism explain allele sharing across species. Here, we explore the sharing of single nucleotide polymorphisms (SNPs) between the major East African cichlid assemblages. A set of approximately 200 genic and nongenic SNPs was ascertained in five Lake Malawi species and genotyped in a diverse collection of ∼160 species from across Africa. We observed segregating polymorphism outside of the Malawi lineage for more than 50% of these loci; this holds similarly for genic versus nongenic SNPs, as well as for SNPs at putative CpG versus non-CpG sites. Bayesian and principal component analyses of genetic structure in the data demonstrate that the Lake Malawi endemic flock is not monophyletic and that river species have likely contributed significantly to Malawi genomes. Coalescent simulations support the hypothesis that river cichlids have transported polymorphism between lake assemblages. We observed strong genetic differentiation between Malawi lineages for approximately 8% of loci, with contributions from both genic and nongenic SNPs. Notably, more than half of these outlier loci between Malawi groups are polymorphic outside of the lake. Cichlid fishes have evolved diversity in Lake Malawi as new mutations combined with standing genetic variation shared across East Africa.
[ "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
174246
Resource and cost effective conversion of biomass to hydrocarbontm oil
The ambition for the Project is to pave-the-way for commercialization and implementation of Steeper Energy Aps (SEA) innovative hydrothermal liquefaction technology platform: HydrofactionTM. The proprietary technology is a highly efficient method to produce renewable fuel oil with similarities to petroleum fuel oils. Timely commercialization will be achieved by bringing Hydrofaction to market via testing, scale-up and demonstration. Based on a proven new chemical process, using renewable low-cost (non-food) feedstocks, Hydrofaction Oil can be burned in CHP applications, used a substitute for low-sulphur marine diesel or may be upgraded to diesel or jet via traditional petroleum refineries. The Project will advance the design of the Hydrofaction technology platform and mature the Company’s preparedness to attract new investment while moving the TRL level from 6 to 8: a critical step toward the commercialization of Hydrofaction. The Project objectives include adjusting the product offering to meet the needs of technology users (licensees) and their customers (oil buyers) by lowering the risks associated with the performance of future commercial plants as well as improving or modifying the quality of Hydrofaction Oil. Within the design of the Project, Hydrofaction Oil will be produced from feedstocks provided by potential commercial partners as well as comprehensive testing of that oil at certified laboratories. Future licensees expect that the scaled demonstration plant, approximately 100 times larger than SEA’s current Pilot facility or 5.000 fuel tonne export capacity, will be representative in both physical design and operations to subsequent full-scale commercial plants to be based on 50.000 fuel tonne export modules transforming large amounts of biomass residuals to Hydrofaction Oil for oil refineries to upgrade to renewable diesel. Key milestones include advancing existing business partner/licensee/project relationships to signed LOIs and MOUs.
[ "Products and Processes Engineering", "Biotechnology and Biosystems Engineering" ]
W2090416936
Human development and cross-border acquisitions
Abstract We examine the role of human development in US companies' decisions to engage in cross-border acquisitions. Utilizing the human development index (HDI) published by the United Nations Development Program (UNDP), we find that US firms make acquisitions in countries with strong HDI levels. Alternative factors such as institutional quality, life expectancy, telephone usage and school enrolments also have a positive influence on the cross-border acquisition decision. Further, we find a positive relationship between cross-border mergers and acquisitions (M&As) and HDI rankings relative to the United States. Our findings contribute to the literature that seeks to explain why so little capital flows from developed to developing economies.
[ "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
interreg_1507
Green public procurement for resource-efficient regional growth
GREEN PUBLIC PROCUREMENT TO ACHIEVE GREEN GROWTH: _x000D_ Since April 2016, the new EU public procurement system generates new opportunities for public administrations to incentivise eco-innovation and resource efficiency via green public procurement (GPP), i.e. by applying new environmental criteria in tenders. GPP4Growth regions are called to play an important role, using their purchasing power to choose green goods & services, and promote sustainable consumption & production patterns. _x000D_ _x000D_ PROJECT OBJECTIVE:_x000D_ GPP4Growth brings together 9 partners from 9 countries, involving the managing authorities & regional bodies influencing regional & national policy instruments, to exchange experiences & practices, and improve their capacity on implementing resource efficiency policies that promote eco-innovation and green growth through GPP. _x000D_ _x000D_ EXPECTED CHANGES: _x000D_ Over 7% increase in the number of businesses in partners’ regions, integrating environmental factors and costs when producing goods and/or providing supplies, services and works. Increased capacity of 200 staff of public administrations to effectively implement resource efficiency policies, applying GPP. 10+Meuros of investments unlocked to promote new green products and services development. Increased knowledge awareness of over 1000 stakeholders on the influence of GPP on the adoption of sustainable consumption and production patterns by businesses. _x000D_ _x000D_ MAIN OUTPUTS & BENEFITS: _x000D_ 3 interregional workshops, 2 existing experience visits & 1 regions summit to promote experiences exchanges of partners and stakeholders. 9 action plans to improve the addressed policy instruments, benefiting managing authorities and beneficiaries. 14 policy briefs to transfer GPP4Growth lessons learnt to public authorities beyond the partnership. A digital lifecycle costing (LCC) method and resources for all EU public administrations to allow harmonised application of LCC. 5 thematic studies & analyses on practices that improve effectiveness of GPP.
[ "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution", "Institutions, Governance and Legal Systems" ]
10.1063/1.4915141
The Same Number Of Optimized Parameters Scheme For Determining Intermolecular Interaction Energies
We propose the Same Number Of Optimized Parameters (SNOOP) scheme as an alternative to the counterpoise method for treating basis set superposition errors in calculations of intermolecular interaction energies. The key point of the SNOOP scheme is to enforce that the number of optimized wave function parameters for the noninteracting system is the same as for the interacting system. This ensures a delicate balance between the quality of the monomer and dimer finite basis set calculations. We compare the SNOOP scheme to the uncorrected and counterpoise schemes theoretically as well as numerically. Numerical results for second-order Moller-Plesset perturbation theory (MP2) and coupled-cluster with single, double, and approximate triple excitations (CCSD(T)) show that the SNOOP scheme in general outperforms the uncorrected and counterpoise approaches. Furthermore, we show that SNOOP interaction energies calculated using a given basis set are of similar quality as those determined by basis set extrapolation of counterpoise-corrected results obtained at a similar computational cost.
[ "Physical and Analytical Chemical Sciences", "Fundamental Constituents of Matter" ]
10.1021/ja4118335
Reaction of a bridged frustrated lewis pair with nitric oxide: A kinetics study
Described is a kinetics and computational study of the reaction of NO with the intramolecular bridged P/B frustrated Lewis pair (FLP) endo-2- (dimesitylphosphino)-exo-3-bis(pentafluorophenyl)boryl-norbornane to give a persistent FLP-NO aminoxyl radical. This reaction follows a second-order rate law, first-order in [FLP] and first-order in [NO], and is markedly faster in toluene than in dichloromethane. By contrast, the NO oxidation of the phosphine base 2-(dimesitylphosphino)norbornene to the corresponding phosphine oxide follows a third-order rate law, first-order in [phosphine] and second-order in [NO]. Formation of the FLP-NO radical in toluene occurs with a ΔH â§§ of 13 kcal mol-1, a feature that conflicts with the computation-based conclusion that NO addition to a properly oriented B/P pair should be nearly barrierless. Since the calculations show the B/P pair in the most stable solution structure of this FLP to have an unfavorable orientation for concerted reaction, the observed barrier is rationalized in terms of the reversible formation of a [B]-NO complex intermediate followed by a slower isomerization-ring closure step to the cyclic aminoxyl radical. This combined kinetics/theoretical study for the first time provides insight into mechanistic details for the activation of a diatomic molecule by a prototypical FLP.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
817842
Pathogen-phage cooperation during mammalian infection
Most bacterial pathogens are lysogens, namely carry DNA of active phages within their genome, referred to as prophages. While these prophages have the potential to turn under stress into infective viruses which kill their host bacterium in a matter of minutes, it is unclear how pathogens manage to survive this internal threat under the stresses imposed by their invasion into mammalian cells. In the proposed project, we will study the hypothesis that a complex bacteria-phage cooperative adaptation supports virulence during mammalian infection while preventing inadvertent killing by phages. Several years ago, we uncovered a novel pathogen-phage interaction, in which an infective prophage promotes the virulence of its host, the bacterial pathogen Listeria monocytogenes (Lm), via adaptive behaviour. More recently, we discovered that the prophage, though fully infective, is non-autonomous- completely dependent on regulatory factors derived from inactive prophage remnants that reside in the Lm chromosome. These findings lead us to propose that the intimate cross-regulatory interactions between all phage elements within the genome (infective and remnant), are crucial in promoting bacteria-phage patho-adaptive behaviours in the mammalian niche and thereby bacterial virulence. In the proposed project, we will investigate specific cross-regulatory and cooperative mechanisms of all the phage elements, study the domestication of phage remnant-derived regulatory factors, and examine the hypothesis that they collectively form an auxiliary phage-control system that tempers infective phages. Finally, we will examine the premise that the mammalian niche drives the evolution of temperate phages into patho-adaptive phages, and that phages that lack this adaptation may kill host pathogens during infection. This work is expected to provide novel insights into bacteria-phage coexistence in mammalian environments and to facilitate the development of innovative phage therapy strategies.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1152/jn.00557.2013
Perception-action dissociation generalizes to the size-inertia illusion
Two objects of similar visual aspects and of equal mass, but of different sizes, generally do not elicit the same percept of heaviness in humans. The larger object is consistently felt to be lighter than the smaller, an effect known as the "size-weight illusion. " When asked to repeatedly lift the two objects, the grip forces were observed to adapt rapidly to the true object weight while the size-weight illusion persisted, a phenomenon interpreted as a dissociation between perception and action. We investigated whether the same phenomenon can be observed if the mass of an object is available to participants through inertial rather than gravitational cues and if the number and statistics of the stimuli is such that participants cannot remember each individual stimulus. We compared the responses of 10 participants in 2 experimental conditions, where they manipulated 33 objects having uncorrelated masses and sizes, supported by a frictionless, air-bearing slide that could be oriented vertically or horizontally. We also analyzed the participants' anticipatory motor behavior by measuring the grip force before motion onset. We found that the perceptual illusory effect was quantitatively the same in the two conditions and observed that both visual size and haptic mass had a negligible effect on the anticipatory gripping control of the participants in the gravitational and inertial conditions, despite the enormous differences in the mechanics of the two conditions and the large set of uncorrelated stimuli.
[ "The Human Mind and Its Complexity", "Neuroscience and Disorders of the Nervous System" ]
10.1021/acs.jpcb.5b01335
A hidden state in light-harvesting complex II revealed by multipulse spectroscopy
Light-harvesting complex II (LHCII) is pivotal both for collecting solar radiation for photosynthesis, and for protection against photodamage under high light intensities (via a process called nonphotochemical quenching, NPQ). Aggregation of LHCII is associated with fluorescence quenching, and is used as an in vitro model system of NPQ. However, there is no agreement on the nature of the quencher and on the validity of aggregation as a model system. Here, we use ultrafast multipulse spectroscopy to populate a quenched state in unquenched (unaggregated) LHCII. The state shows characteristic features of lutein and chlorophyll, suggesting that it is an excitonically coupled state between these two compounds. This state decays in approximately 10 ps, making it a strong competitor for photodamage and photochemical quenching. It is observed in trimeric and monomeric LHCII, upon re-excitation with pulses of different wavelengths and duration. We propose that this state is always present, but is scarcely populated under low light intensities. Under high light intensities it may become more accessible, e. g. by conformational changes, and then form a quenching channel. The same state may be the cause of fluorescence blinking observed in single-molecule spectroscopy of LHCII trimers, where a small subpopulation is in an energetically higher state where the pathway to the quencher opens up.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1007/s10803-020-04718-7
Pupillary Responses Obey Emmert’s Law and Co-vary with Autistic Traits
We measured the pupil response to a light stimulus subject to a size illusion and found that stimuli perceived as larger evoke a stronger pupillary response. The size illusion depends on combining retinal signals with contextual 3D information; contextual processing is thought to vary across individuals, being weaker in individuals with stronger autistic traits. Consistent with this theory, autistic traits correlated negatively with the magnitude of pupil modulations in our sample of neurotypical adults; however, psychophysical measurements of the illusion did not correlate with autistic traits, or with the pupil modulations. This shows that pupillometry provides an accurate objective index of complex perceptual processes, particularly useful for quantifying interindividual differences, and potentially more informative than standard psychophysical measures.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity" ]
EP 81810513 A
VAT AND SULPHUR DYESTUFF PREPARATIONS
Beschrieben werden spezifische Verküpungsbeschleuniger gemäss den Ansprüchen 1 und 2. Diese können einer Küpen- oder Schwefelfarbstoffzubereitung oder einem Färbebad oder Druckpaste enthaltend Küpen- bzw. Schwefelfarbstoffe zugesetzt werden womit eine Verbesserung der Farbausbeute vor allem auf Cellulosematerialien erzielt wird.
[ "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
TW 102105933 A
An ophthalmic lens with segmented ring layers in a functionalized insert
An active lens insert for an ophthalmic lens is described. The lens comprising: arcuate shape ring segments assembled into substrate layers with one or both of electrical and logical functionality; wherein the size, shape and stacking structure of each of the annular shaped substrate layers is based on the thickness around an optical zone of the ophthalmic lens; electrical interconnections between substrate layers; and wherein the active lens insert is encapsulated with one or more materials for bonding within the body material of a molded ophthalmic lens.
[ "Products and Processes Engineering", "Materials Engineering", "Systems and Communication Engineering" ]
10.1016/j.buildenv.2011.08.009
Relating material experience to technical parameters: A case study on visual and tactile warmth perception of indoor wall materials
Experiential aspects of materials are addressed rather intuitively by architects during the material selection process for buildings. This paper explores the possibilities of relating material experience in architecture to technical material parameters and uses the perceived warmth of indoor wall materials as a case study. Various building materials were assessed technically and their perceived warmth was evaluated by participants. As people experience a building and its materials through multiple senses, the separate effects of vision and touch were considered. Results show that the senses used for evaluation have a major impact on the perception of warmth, and that a distinction should be made between the visual warmth and tactile warmth of a material. The overall perception of warmth was shown to correspond to its visual perception. Furthermore, the perception of material warmth was correlated with several technical material parameters, such as the thermal effusivity, the surface gloss and the hue and saturation of the material color. The color study suggested that the material color has a larger effect on the perceived warmth than other material parameters. An indication of the relationships between the perceived material warmth and measurable technical material parameters offers architects insights on how to change the experience of warmth by changing specific technical parameters and thus allows to select materials in a better informed way.
[ "Materials Engineering", "Products and Processes Engineering", "Physical and Analytical Chemical Sciences" ]
10.1155/2016/3572827
High Yielding Microbubble Production Method
Microfluidic approaches to microbubble production are generally disadvantaged by low yield and high susceptibility to (micro)channel blockages. This paper presents an alternative method of producing microbubbles of 2. 6 μm mean diameter at concentrations in excess of 30 × 106 mL−1. In this method, the nitrogen gas flowing inside the liquid jet is disintegrated into spray of microbubble when air surrounding this coflowing nitrogen gas-liquid jet passes through a 100 μm orifice at high velocity. Resulting microbubble foam has the polydispersity index of 16%. Moreover, a ratio of mean microbubble diameter to channel width ratio was found to be less than 0. 025, which substantially alleviates the occurrence of blockages during production.
[ "Physical and Analytical Chemical Sciences", "Products and Processes Engineering" ]
10.1093/esr/jcaa023
Economic Exchange or Gender Identities? Housework Division and Wives’ Economic Dependency in Different Contexts
This paper explores cross-country variation in the relationship between division of housework and wives’ relative economic contribution. Using ISSP 2012 data from 19 countries, we examined the effect of two contextual factors: women’s employment rates, which we link to economic exchange theories; and gender ideology context, which we link to cultural theories. In line with economic-based theories, economic exchange between housework and paid work occurs in all countries—but only in households which follow normative gender roles. However, and consistent with the cultural-based theory of ‘doing gender’, wives undertake more housework than their spouses in all countries—even if they are the main or sole breadwinners. This universal gendered division of housework is significantly more salient in more conservative countries; as the context turns more conservative, the gender gap becomes more pronounced, and the relationship between paid and unpaid work further removed from the economic logic. In gender egalitarian societies, in contrast, women have more power in negotiating housework responsibilities in non-normative gender role households. In contrast to gender ideology, the cross-country variations in women’s employment did not follow the expectations that derive from the economic exchange theory.
[ "The Social World and Its Interactions", "Individuals, Markets and Organisations" ]
10.1038/nature07636
Electrically pumped photonic-crystal terahertz lasers controlled by boundary conditions
Semiconductor lasers based on two-dimensional photonic crystals generally rely on an optically pumped central area, surrounded by un-pumped, and therefore absorbing, regions. This ideal configuration is lost when photonic-crystal lasers are electrically pumped, which is practically more attractive as an external laser source is not required. In this case, in order to avoid lateral spreading of the electrical current, the device active area must be physically defined by appropriate semiconductor processing. This creates an abrupt change in the complex dielectric constant at the device boundaries, especially in the case of lasers operating in the far-infrared, where the large emission wavelengths impose device thicknesses of several micrometres. Here we show that such abrupt boundary conditions can dramatically influence the operation of electrically pumped photonic-crystal lasers. By demonstrating a general technique to implement reflecting or absorbing boundaries, we produce evidence that whispering-gallery-like modes or true photonic-crystal states can be alternatively excited. We illustrate the power of this technique by fabricating photonic-crystal terahertz (THz) semiconductor lasers, where the photonic crystal is implemented via the sole patterning of the device top metallization. Single-mode laser action is obtained in the 2. 55-2. 88 THz range, and the emission far field exhibits a small angular divergence, thus providing a solution for the quasi-total lack of directionality typical of THz semiconductor lasers based on metal-metal waveguides.
[ "Condensed Matter Physics", "Systems and Communication Engineering" ]
10.1126/science.aav9518
Amyloid b oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes
Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid b (Ab) constricts brain capillaries at pericyte locations. This was caused by Ab generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Ab could potentially reduce energy lack and neurodegeneration in AD.
[ "Neuroscience and Disorders of the Nervous System", "Physiology in Health, Disease and Ageing" ]
215776
Enhanced bioconversion of agricultural residues through cascading use
The BIOrescue project aims to develop and demonstrate a new innovative biorefinery concept based on the cascading use of spent mushroom substrate (SMS) supplemented by wheat straw (and other seasonal underutilised lignocellulosic feedstocks. i.e pruning residues, residual citrus peels and wastes). This new concept will avoid disposal and allow for the production of some biodegradable bio-based products and bioactive compounds that will help to replace the existing ones based on fossil resources. The research will help to expand the business opportunities of the mushroom cultivation farms, and the know-how and business opportunities of all the partners involved. The main innovations are: - Improved methods for the lab-based rapid (NIR) analysis of biomass - Innovative two step fractionation of SMS - Synergic effects for complete SMS glucan hydrolysis - Innovative enzyme immobilisation strategy - Development of highly efficient glucan-enzymes - Novel lignin based nano- and micro-carriers - Biopesticide production from monomeric sugars SMS derived and their packaging into nanocarriers The consortium involved is a representation of some BIC members including a large company (Monaghan Mushrooms) which is leading the proposal and some SMEs (MetGen Oy and CLEA Technologies) and BIC associate members (University of Naples and CENER). Additionally other relevant partners with well-known expertise in their respective areas contribute to the objectives. Among them some research organisations (Imperial College of London and Max Planck Institute of Polymers) and Innovative SMEs (Celignis Limited, Zabala Innovation Consulting, Greenovate Europe and C-TECH Innovation Ltd). The synergies between large industry and SME’s go beyond the scope of this project. There is a lot of potential for collaboration between agricultural industry (Monaghan) and biotechnology (MetGen and CLEA) to provide novel solutions for continuous circular economy in large agriculture-based value-chains.
[ "Biotechnology and Biosystems Engineering", "Environmental Biology, Ecology and Evolution", "Products and Processes Engineering", "Materials Engineering" ]
W2062084074
The age prospective memory paradox within the same sample in time-based and event-based tasks
The present research investigated the age prospective memory (PM) paradox by testing the performance of the same participants on laboratory and naturalistic PM tasks. Younger, middle-aged, and older adults performed three tasks (time-based, event-based with focal cue, and event-based with nonfocal cue); first in the laboratory, then in the context of their everyday lives. Additionally, the social importance of PM tasks was manipulated in the laboratory. As expected, age-dependent declines on the laboratory tasks were reversed in the naturalistic tasks. Middle-aged adults performed as well as younger adults in the laboratory and as well as the elderly outside of the laboratory. When the social importance of laboratory tasks was stressed, the performance of younger adults fell. In addition, older adults showed higher self-reported commitment to the naturalistic tasks than both younger and middle-aged adults. Findings are discussed in the context of possible explanations for the age PM paradox.
[ "The Human Mind and Its Complexity", "Neuroscience and Disorders of the Nervous System" ]
173356
Synchronisation to enhance reliability of climate predictions
Climate prediction is the next frontier in climate research. Prediction of climate on timescales from a season to a decade has shown progress, but beyond the ocean skill remains low. And while the historical evolution of climate at global scales can be reasonably simulated, agreement at a regional level is limited and large uncertainties exist in future climate change. These large uncertainties pose a major challenge to those providing climate services and to informing policy makers. This proposal aims to investigate the potential of an innovative technique to reduce model systematic error, and hence to improve climate prediction skill and reduce uncertainties in future climate projections. The current practice to account for model systematic error, as for example adopted by the Intergovernmental Panel on Climate Change, is to perform simulations with ensembles of different models. This leads to more reliable predictions, and to a better representation of climate. Instead of running models independently, we propose to connect the different models in manner that they synchronise and errors compensate, thus leading to a model superior to any of the individual models – a super model. The concept stems from theoretical non-dynamics and relies on advanced machine learning algorithms. Its application to climate modelling has been rudimentary. Nevertheless, our initial results show it holds great promise for improving climate prediction. To achieve even greater gains, we will extend the approach to allow greater connectivity among multiple complex climate models to create a true super climate model. We will assess the approach’s potential to enhance seasonal-to-decadal prediction, focusing on the Tropical Pacific and North Atlantic, and to reduce uncertainties in climate projections. Importantly, this work will improve our understanding of climate, as well as how systematic model errors impact prediction skill and contribute to climate change uncertainties.
[ "Computer Science and Informatics", "Earth System Science" ]
US 19322994 A
Electromagnetic radiation absorbers and modulators comprising polyaniline
A method of providing electronic shielding comprising providing a layer of a polyaniline composition on the object to be shielded, whereby the entrance and egress of electromagnetic radiation is prevented. Also presented herein is a method of changing the absorption by a polyaniline composition of electromagnetic radiation by modifying the chemical structure and crystallinographic order of the polyaniline composition, wherein said composition comprises a composition of the formula <IMAGE> where y can be equal to or greater than zero, and R1 and R2 are independently selected from the group consisting of -H, -OCH3, -F, -Cl, -Br, -I, -NR32, -NHCOR3, -OH, -O, -SR3, -OR3, -OCOR3, -NO2, -COOH, -COOR3, -R3SO3H, -COR3, -CHO, and -CN, where R3 is a C1 to C8 alkyl, aryl, or aralkyl group.
[ "Synthetic Chemistry and Materials", "Materials Engineering", "Physical and Analytical Chemical Sciences" ]
10.1016/j.jsb.2010.12.004
Structural insights into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase
The Na+,K+-ATPase belongs to the P-ATPase family, whose characteristic property is the formation of a phosphorylated intermediate. The enzyme is also a defined target for cardiotonic steroids which inhibit its functional activity and initiate intracellular signaling. Here we describe the 4. 6Å resolution crystal structure of the pig kidney Na+,K+-ATPase in its phosphorylated form stabilized by high affinity binding of the cardiotonic steroid ouabain. The steroid binds to a site formed at transmembrane segments αM1-αM6, plugging the ion pathway from the extracellular side. This structure differs from the previously reported low affinity complex with potassium. Most importantly, the A domain has rotated in response to phosphorylation and αM1-2 move towards the ouabain molecule, providing for high affinity interactions and closing the ion pathway from the extracellular side. The observed re-arrangements of the Na+,K+-ATPase stabilized by cardiotonic steroids may affect protein-protein interactions within the intracellular signal transduction networks.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
interreg_3837
Urban-rural partnerships in metropolitan areas
The URMA-project promotes urban-rural partnerships as a tool to strengthen the potential for generation and transfer of innovation in European metropolitan areas and their surrounding hinterlands. The basis was laid during a preceding project, integrated in the action programme “Pilot Project of Spatial Planning” sponsored by the German Federal Ministry of Transport, Building and Urban Development. In this project regional disparities were tackled and the effectiveness of regional development policies was improved by new governance structures for large scale urban-rural partnerships (triple helix approach). Balancing regional disparities and being competitive at the same time are challenges for all regions in Europe and therefore the project theme is of high interest to many other metropolitan areas. The project’s objective is therefore to utilize the urban-rural cooperation schemes developed and tested in the above-named project and in other partner regions in the field of innovation generation and transfer within metropolitan areas and regional urban-rural networks. The PP will identify different types of regional innovation systems, exchange experiences on urban-rural cooperation and finally help to improve the effectiveness of regional and local policies in the field of innovation. This objective enables an establishment of a regional, national and European policy agenda for a sustainable development of metropolitan areas. Moreover, it will result in lasting and balanced positive effects on the competiveness of metropolitan areas, also in global terms. The key advantage to this approach is that urban and rural areas will benefit on equal terms and that cities will not gain competitiveness on the expense of urban areas and vice-versa. The participating nine PP from five EU member states (BG,DE,IT,NL,PL) cover a wide EU area and are directly involved in the improvement of regional policies. The consortium is homogenous and diverse at the same time, comprising differently shaped urban-rural regions, from strong interconnected metropolitan areas to smaller city regions. The mix of larger and smaller, well experienced and less experienced PP will open up new possibilities of learning and knowledge transfer and creates an added value for all regions. URMA is mainly focused on the exchange of experiences through an array of conferences, public and project internal workshops, study visits in all regions and 3 pilot implementations. The cooperation will be supported by a common toolkit to identify and describe best practices, a concise dictionary and a Good Practice Guide. Furthermore recommendations for the whole project partnership with regard to regional innovation systems and for the future European cohesion policy regarding urban-rural partnerships will be developed. All in all, the project will raise the awareness for the need and potential of urban-rural partnerships – a new approach to strengthen innovation in European metropolitan areas.
[ "Human Mobility, Environment, and Space", "Institutions, Governance and Legal Systems", "Individuals, Markets and Organisations" ]
W2603990139
The suitability of cloud, massive and moderate computing environments for SKA scale data
We present the results of our investigations into options for the computing platform for the imaging pipeline in the CHILES project, an ultra-deep HI pathfinder for the era of the Square Kilometre Array. CHILES pushes the current computing infrastructure to its limits and understanding how to deliver the images from this project is clarifying the Science Data Processing requirements for the SKA. We have tested three platforms: a moderately sized cluster, a massive High Performance Computing (HPC) system, and the Amazon Web Services (AWS) cloud computing platform. We are able to complete the imaging pipeline processing on both the HPC platform and also on the cloud computing platform, which paves the way for meeting big data challenges in the era of SKA in the field of Radio Astronomy.
[ "Universe Sciences", "Computer Science and Informatics" ]
10.1039/C8PY00278A
A Biocompatible Diazosulfonate Initiator For Direct Encapsulation Of Human Stem Cells Via Two Photon Polymerization
Direct cell encapsulation is a powerful tool for fabrication of biomimetic 3D cell culture models in vitro. This method allows more precise recapitulation of the natural environment and physiological functions of cells compared to classical 2D cultures. In contrast to seeding cells on prefabricated scaffolds, cell encapsulation offers benefits regarding high initial cell loading, uniformity of cell distribution and more defined cell–matrix contact. Two-photon polymerization (2PP) based 3D printing enables the precise engineering of cell-containing hydrogel constructs as tissue models. Two-photon initiators (2PIs) specifically developed for this purpose still exhibit considerable cyto- and phototoxicity, impairing the viability of encapsulated cells. This work reports the development of the first cleavable diazosulfonate 2PI DAS, largely overcoming these limitations. The material was characterized by standard spectroscopic methods, white light continuum two-photon absorption cross-section measurements, and its photosensitization of cytotoxic singlet oxygen was compared to the well-established 2PI P2CK. When DAS is used at double concentration to compensate for the lower two-photon cross section, its performance in 2PP-printing of hydrogels is similar to P2CK based on structuring threshold and structure swelling measurements. PrestoBlue metabolic assay showed vastly improved cytocompatibility of DAS in 2D. Cell survival in 3D direct encapsulation via 2PP was up to five times higher versus P2CK, further demonstrating the excellent biocompatibility of DAS and its potential as superior material for laser-based biofabrication.
[ "Materials Engineering", "Cell Biology, Development, Stem Cells and Regeneration", "Synthetic Chemistry and Materials" ]
W1565843436
Prevalence of third molars and pathological changes related to them in dental medicine.
The purpose of this study was to determine the prevalence of third molars in terms of respondents' age. Furthermore it was desired to determine the extent of the manifestation of pathological changes, such as caries, apical lesions, and alveolar bone resorption. This study was based on 500 OPGs of patients from the Faculty of Dentistry, University of Zagreb. Patients were divided into seven age groups. The total number of molars, the number of cavities on remaining molars, the quality of endodontic treatment and the evaluation of their performance and presence of periapical lesions was analyzed. As apart of the periodontal status, the number of inadequate fillings, the number of damaged furcations and bone resorption was analyzed. The statistical analysis was performed by means of STATISTICA 7 statistical package (StatSoft, Tulsa, USA). The correlation between the total number of molars and the age of patients was analyzed by means of Spearman's correlation to the level of significance of 0.05. The number of first, second and third molars significantly decreased in higher age groups. The prevalence of caries in third molars as compared to first and second molars was generally lower, third molars were endodontic treated at least. Assessment of involved furcations showed that the lowest percentage of 8% was found in third molars. The majority of all remaining molars had bone resorption of 1-3 mm.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physiology in Health, Disease and Ageing" ]
171227
Liquid ring compressor - pioneering full api-681/610 compliance
Our company, Emmecom Srl, has tremendously changed since its creation: established in 2001 in Cologno Monzese (near Milan, Italy) as a reseller of industrial goods and limited to Lombardy-region based customers, we have experience during the last decade a remarkable growth to become an international company (presence in Italy and China) designing, producing and selling pumps, compressors and vacuum systems. This consistent growth, supported by our excellence in key technologies such as the liquid ring pumps, has transformed our business figures from €2.1million in 2009 to €5.2 million in 2014. Listening to customer’s feedback from the Oil & Gas and petrochemical sector, we have been developing, since 2010, an innovating portfolio of Liquid Ring Compressors & Pumps to address their needs: liquid ring based solutions are preferred solutions for critical applications in chemical, petrochemical and refinery industries as they are highly reliable and easy to maintain; nonetheless, their limited efficiency – and therefore high energy intake – due to inner turbulence still hinders their growth against traditional solutions. LIRICO, our innovative two-stage Liquid Ring Compressor/Pump, represents the next step: its increase in volumetric efficiency (+5%) and in output pressure (+15%) allows a drastic reduction in energy consumption (-25%) and in overall casing volume (-30%). Fully compliant to API681 and API610, LIRICO will allow us to provide a competitive, highly efficient, with even reduced downtime solution, subsequentely increasing our sales by 15% within 5 years.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1021/acssuschemeng.9b07494
Chemoenzymatic Halocyclization of 4-Pentenoic Acid at Preparative Scale
The scale-up of chemoenzymatic bromolactonization to 100 g scale is presented, together with an identification of current limitations. The preparative-scale reaction also allowed for meaningful mass balances identifying current bottlenecks of the chemoenzymatic reaction.
[ "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
W1791397770
Business models for district heating
Although district heating (DH) as a technology has shown considerable competitive attractiveness, it is a delicate task to develop an efficient, profitable, and customer-oriented district heating firm. Even in mature markets where DH has a dominant position, the difficulties have increased due to global warming, competing technologies, and changing customer preferences. In this chapter, we present the results and theoretical implications of a 3-year long research project that explored the strategic decisions made by managers working in Swedish DH firms that have, to a large degree, met such challenges, in one of the world’s most deregulated energy markets, in a successful way. We also present two analytical concepts: the business model and business logic, as a means to understand the DH business and its possibilities for development. These concepts are contextualized in order to fit with aspects unique to district heating and cooling (DHC). Although helpful for understanding the core business, we suggest that a dominant industry-specific “business logic” should guide managers when they are making decisions on how to reshape their business models. Furthermore, several innate features of the DHC business accentuate the need for managers to act in a strategic manner and build long-term stable relationships with stakeholders, in order to be able to meet complex challenges through realizing complex business opportunities.
[ "Individuals, Markets and Organisations", "Products and Processes Engineering" ]
896067
Software platform for multiscale modelling of reactive materials and processes
Reactive process design has largely been based on trial-and-error experimentation and similarly, reactor design has utilised empirical kinetics (data-based models). On the other hand, physics-based modelling approaches are emerging as highly promising in the development of new catalytic materials and reactive processes, and it would be desirable to be able to use high-fidelity, first-principles-based reactor scale simulations for process design. Multi-equation models are steadily gaining ground in the chemical reaction engineering community, combining mature tools at each scale, from the molecular up to the reactor. However, such efforts are currently restricted to academia; a commercial modelling suite and software platform, accessible to the generalist user, is lacking. To address this challenge, ReaxPro has identified a set of academic software tools (EON, Zacros, CatalyticFOAM) which will be upscaled into easy-to-learn, user friendly, interoperable software that is supported and well documented. These tools will be further integrated with commercial software (ADF Modeling Suite) into an industry-ready solution for catalytic material and process design. The ReaxPro Software platform and associated services will be made available via the European Materials Modelling Marketplace through the consortium's partnership with ongoing EU projects MARKETPLACE and VIMMP. To fully reach the target technology readiness level of 7, ReaxPro has partnered with translators and industry for validation and demonstration in pilot- and industrial-scale user cases. As a result of the proposed activities, academia and industry will have at their disposal an integrated, interoperable, customisable and modular modelling platform, enabling users to gain unique fundamental insight on reactive processes, but also a ready-to-use tool for the design of cost-efficient, environmentally friendly and sustainable processes, delivering measurable impact on the entire EU economy.
[ "Physical and Analytical Chemical Sciences", "Products and Processes Engineering", "Computer Science and Informatics" ]
945602
Pathogen-responsive hydrogels release antimicrobial vesicles for local infection treatment
The rise of bacterial resistance against antibiotic drugs is becoming the leading cause for morbidity and mortality worldwide. In Europe alone, up to 33,000 people die each year from infections with resistant bacteria. Current antibiotic therapy often suffers from low selectivity, adverse side effects in other organs and impaired ability to overcome bacterial barriers. These problems limit the efficacy of our antibiotic arsenal. Local and effective eradication of bacterial infections is of utmost importance to avert the formation of new resistances. My research centres on naturally derived vesicles. All living cells and microorganisms produce these nanoparticles and equip them with unique features for transport and targeted delivery of molecules. I have previously discovered a new group of bacteria-derived vesicles with low cytotoxicity and inherent antibiotic activity. Upon contact with culture supernatant from pathogens, bacteria produce higher potent antimicrobial vesicles. Now, I would like to incorporate these vesicles into hydrogels – Gels4Bac – that respond to pathogenic factors in the infection environment. Once the hydrogel encounters these factors, antimicrobial vesicles are selectively and locally released in the presence of specific pathogens. The local application reduces time until treatment, adverse side effects and unspecific killing of beneficial microbiota. Gels4Bac will create new options for selectively treating infectious dispositions. Stimulation of vesicle producing bacteria with pathogen-derived components may open an on-demand customisable, quick and cost-effective approach for treatment. In addition, it creates new avenues for the discovery of novel antimicrobial agents besides current screening and medicinal chemistry. Such platform technology is imperative to equip Europe in its fight against the rise of infections with resistant bacteria, and will boost Europe's scientific competitiveness in infection therapy.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Materials Engineering" ]
10.1158/0008-5472.CAN-16-2946
Sarcoma Eradication By Doxorubicin And Targeted Tnf Relies Upon Cd8 T Cell Recognition Of A Retroviral Antigen
Antibody-cytokine complexes may offer new tools to treat cancer. Here, we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37). Notably, cured mice were resistant to rechallenge not only by WEHI-164 cells but also heterologous C51 or CT26 colorectal tumor cells in a CD8+ T-cell-dependent process. Mechanistic analyses revealed that each tumor cell line presented AH1, a common endogenous retroviral peptide. Numbers of AH1-specific CD8+ T cells exhibiting cytotoxic capacity were increased by F8-TNF plus doxorubicin treatment, arguing that cognate CD8+ T cells contributed to tumor eradication. Sequence analysis of T-cell receptors of CD8+ T cells revealed the presence of H-2Ld/AH1-specific T cells and an expansion of sequence diversity in treated mice. Overall, our findings provide evidence that retroviral genes contribute to tumoral immunosurveillance in a process that can be generally boosted by F8-TNF and doxorubicin treatment. Cancer Res; 77(13); 3644-54.
[ "Immunity, Infection and Immunotherapy", "Prevention, Diagnosis and Treatment of Human Diseases", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1371/journal.pgen.1005445
The Evolutionary Potential of Phenotypic Mutations
Errors in protein synthesis, so-called phenotypic mutations, are orders-of-magnitude more frequent than genetic mutations. Here, we provide direct evidence that alternative protein forms and phenotypic variability derived from translational errors paved the path to genetic, evolutionary adaptations via gene duplication. We explored the evolutionary origins of Saccharomyces cerevisiae IDP3 - an NADP-dependent isocitrate dehydrogenase mediating fatty acids ß-oxidation in the peroxisome. Following the yeast whole genome duplication, IDP3 diverged from a cytosolic ancestral gene by acquisition of a C-terminal peroxisomal targeting signal. We discovered that the pre-duplicated cytosolic IDPs are partially localized to the peroxisome owing to +1 translational frameshifts that bypass the stop codon and unveil cryptic peroxisomal targeting signals within the 3’-UTR. Exploring putative cryptic signals in all 3’-UTRs of yeast genomes, we found that other enzymes related to NADPH production such as pyruvate carboxylase 1 (PYC1) might be prone to peroxisomal localization via cryptic signals. Using laboratory evolution we found that these translational frameshifts are rapidly imprinted via genetic single base deletions occurring within the very same gene location. Further, as exemplified here, the sequences that promote translational frameshifts are also more prone to genetic deletions. Thus, genotypes conferring higher phenotypic variability not only meet immediate challenges by unveiling cryptic 3’-UTR sequences, but also boost the potential for future genetic adaptations.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
interreg_2362
Guiding Mediterranean MPAs through the climate change era: Building resilience and adaptation
The Mediterranean Sea climate will undergo rapid changes over the next decades. Direct evidence of climate change (CC) is already being observed at Mediterranean coast, including marine protected areas (MPAs). The need for building resilience in both social and ecological aspects of MPAs, through taking on adaptive management thus becomes an essential element for mitigating against and adjusting to the rapid changes to maintain and protect healthy ecosystems. However, CC is not explicit incorporated in most management plans and information to assist MPA decision making is both limited and fragmented.The goals of the MPA-Adapt are to develop collaborative and site-specific adaptation plans for the MPAs that enhance resilience to CC impacts. This will be achieved by building capacity for effective management, assessing risks- and exploring potential actions and priorities needed to ensure the adaptability and the resilience of biodiversity and the local communities. It also aims to incorporate CC vulnerability assessments and nature-based adaptation planning into their existing management framework, and provide guidance to MPA managers and local stakeholders to implement and test climate-change approaches. This project is a first of its kind for the marine and coastal Mediterranean environment and will also foster networks by improving the dialogue and coordination between MPA managers and scientists in order to create the first line of Mediterranean MPA sentinel sites.
[ "Earth System Science", "Environmental Biology, Ecology and Evolution" ]
W2005689768
Cysteine coordination of Pb(II) is involved in the PbrR-dependent activation of the lead-resistance promoter, PpbrA, from Cupriavidus metallidurans CH34
The pbr resistance operon from Cupriavidus metallidurans CH34 plasmid pMOL30 confers resistance to Pb(II) salts, and is regulated by the Pb(II) responsive regulator PbrR, which is a MerR family activator. In other metal sensing MerR family regulators, such as MerR, CueR, and ZntR the cognate regulator binds to a promoter with an unusually long spacer between the -35 and -10 sequences, and activates transcription of resistance genes as a consequence of binding the appropriate metal. Cysteine residues in these regulators are essential for metal ion coordination and activation of expression from their cognate promoter. In this study we investigated the interaction of PbrR with the promoter for the structural pbr resistance genes, PpbrA, effects on transcriptional activation of altering the DNA sequence of PpbrA, and effects on Pb(II)-induced activation of PpbrA when cysteine residues in PbrR were mutated to serine.Gel retardation and footprinting assays using purified PbrR show that it binds to, and protects from DNase I digestion, the PpbrA promoter, which has a 19 bp spacer between its -35 and -10 sites. Using β-galactosidase assays in C. metallidurans, we show that when PpbrA is changed to an 18 bp spacer, there is an increase in transcriptional activation both in the presence and absence of Pb(II) salts up to a maximum induction equivalent to that seen in the fully-induced wild-type promoter. Changes to the -10 sequence of PpbrA from TTAAAT to the consensus E. coli -10 sequence (TATAAT) increased transcriptional activation from PpbrA, whilst changing the -10 sequence to that of the Tn501 mer promoter (TAAGGT) also increased the transcriptional response, but only in the presence of Pb(II). Individual PbrR mutants C14S, C55S, C79S, C114S, C123S, C132S and C134S, and a double mutant C132S/C134S, were tested for Pb(II) response from PpbrA, using β-galactosidase assays in C. metallidurans. The PbrR C14S, C79S, C134S, and C132S/C134S mutants were defective in Pb(II)-induced activation of PpbrA.These data show that the metal-dependent activation of PbrR occurs by a similar mechanism to that of MerR, but that metal ion coordination is through cysteines which differ from those seen in other MerR family regulators, and that the DNA sequence of the -10 promoter affects expression levels of the lead resistance genes.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Physical and Analytical Chemical Sciences" ]
10.1016/j.atmosenv.2014.08.007
Proton Transfer Reaction Time-of-Flight Mass Spectrometric (PTR-TOF-MS) determination of volatile organic compounds (VOCs) emitted from a biomass fire developed under stable nocturnal conditions
Combustion of solid and liquid fuels is the largest source of potentially toxic volatile organic compounds (VOCs), which can strongly affect health and the physical and chemical properties of the atmosphere. Among combustion processes, biomass burning is one of the largest at global scale. We used a Proton Transfer Reaction "Time-of-Flight" Mass Spectrometer (PTR-TOF-MS), which couples high sensitivity with high mass resolution, for real-time detection of multiple VOCs emitted by burned hay and straw in a barn located near our measuring station. We detected 132 different organic ions directly attributable to VOCs emitted from the fire. Methanol, acetaldehyde, acetone, methyl vinyl ether (MVE), acetic acid and glycolaldehyde dominated the VOC mixture composition. The time-course of the 25 most abundant VOCs, representing ~85% of the whole mixture of VOCs, was associated with that of carbon monoxide (CO), carbon dioxide (CO2) and methane (CH4) emissions. The strong linear relationship between the concentrations of pyrogenic VOC and of a reference species (i. e. CO) allowed us to compile a list of emission ratios (ERs) and emission factors (EFs), but values of ER (and EF) were overestimated due to the limited mixing of the gases under the stable (non-turbulent) nocturnal conditions. In addition to the 25 most abundant VOCs, chemical formula and concentrations of the residual, less abundant VOCs in the emitted mixture were also estimated by PTR-TOF-MS. Furthermore, the evolution of the complex combustion process was described on the basis of the diverse types of pyrogenic gases recorded.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
W2532660647
Market Access, Well-being, and Nutrition: Evidence from Ethiopia
Summary We use a unique data source from a rural area in northwestern Ethiopia to analyze the relationship between household/individual well-being, nutrition, and market access. We find that households residing in relatively more remote areas consume substantially less than households nearer to the market, they are more food insecure, and their school enrollment rates are lower. Although their diets are also less diverse, we find no significant differences in mother and child anthropometric measures. Part of the differences in well-being that we do observe can be attributed to lower household agricultural production in remote areas. Nonetheless agricultural production differences alone do not account for all the differences in household consumption levels for remote households. An additional contributing factor is the terms of trade for remote households that negatively affect both the size of the agricultural surplus that these households market and the quantity of food items that they purchase. Reducing transaction costs for remote households and facilitating migration could help equalize well-being among more or less favored locations.
[ "Individuals, Markets and Organisations", "Human Mobility, Environment, and Space" ]
636808
From the origin of Earth's volatiles to atmospheric oxygenation
Aim of this project is to understand the connection between endogenic and exogenic processes of our planet that led to the redox contrast between Earth’s surface and interior. For this purpose the time constraints on atmospheric oxygenation can be refined and for the first time linked with a new approach to Earth’s endogenic processes like plate tectonics, mantle melting, volcanism, continent formation and subduction-related sediment- and crust recycling. These objectives will be achieved by using the unique geochemical capabilities of the selenium (Se) isotope system to unlock the geological record of changing oxygen fugacities in the mantle-crust-atmosphere reservoirs. The power of the Se isotope system lies in its redox sensitivity and in the volatile and highly siderophile/chalcophile character of elemental Se. This links Se to the evolution of other volatiles during key geological processes from Earth formation ca. 4.5 Ga ago until today. The occurrence and behavior of Se is fully controlled by accessory micrometric sulfide minerals in the silicate Earth, which may conserve their original Se isotopic signatures over large geological timescales and can be dated via the 187Re-187Os geochronometer. This offers high resolutions in time and space that are groundbreaking for research on Earth System Oxygenation. Covering Earth geologic history, new high-precision Se isotope data of the sedimentary and representative mantle-derived magmatic rock record from all major plate tectonic settings will be combined with the mineral-scale record of robust and global “time capsules” such as diamond inclusions. Once the evolution into todays dynamic Earth’s Redox System is understood, the investigation will be pushed back in time to Earth’s formation. This involves a reconciliation of the meteoritic and Archean rock and mineral-scale Se isotope record to constrain the origin of volatiles essential for the oceans, generation of an atmosphere and development of life on our planet.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
10.1007/s10624-019-09578-x
‘We are not just a union, we are a family’ class, kinship and tribe in Zambia’s mining unions
Trade unions in Zambia and in several other developing countries have been understood to create ‘detribalising’ class consciousnesses. In contrast, we argue that Zambian understandings of unionism have developed through similar political economic processes to those that generated ‘tribes’. Values and structures that enable concepts of the good life more commonly found among Bemba speakers and Eastern Zambians have been naturalised into Zambia’s mining unions, guiding union policy and practice in a manner which limits North Western Zambians’ union participation. Utilising Lazar's (2018) understanding of unionism as kinship, we explore how Zambians of various tribes attempt to utilise unions to achieve what they see as human flourishing and social justice. We foreground that people’s understandings of the good life frequently incorporate gendered and gerontocratic hierarchies and we demonstrate that intra-national unionisms are co-created through (and influence) local cultural norms and political histories. This encourages anthropologists of trade unionism to ask what values and hierarchies are rendered invisible in other union ‘families’, and to explore intertwinements between unions and communities enabled through kinship, rather than through Civil Society Organisations.
[ "The Social World and Its Interactions", "Studies of Cultures and Arts" ]
741273
Detection, simulation, modelling and loading of thunderstorm outflows to design wind-safer and cost-efficient structures
Wind actions are crucial for the safety and cost of structures. The wind climate of Europe and many parts of the world is dominated by synoptic extra-tropical cyclones and mesoscale thunderstorm outflows. Thunderstorms are frequent events causing wind speeds often higher than cyclones. In spite of an impressive amount of research, there is not yet a model for thunderstorm outflows and their actions on structures like that for cyclones. Thus, thunderstorm actions on structures are still determined using the cyclone model developed half a century ago and engineering practice often leads to unsafe or too expensive construction. This happens because the complexity of thunderstorms makes it difficult to develop realistic and simple models. Their short duration and small size make the available data very poor. There is a great gap between research in wind engineering and atmospheric sciences. The realization of an unprecedented wind monitoring network, the role of the PI and his novel vision, a project team leader in wind engineering with interdisciplinary skill in atmospheric sciences, the chance to simulate large-scale thunderstorms in a new unique laboratory, the recent advance in CFD simulations, the success and synergy of previous and on-going projects, and a top host institution represent extraordinary conditions to overcome these shortcomings. THUNDERR is an acronym of THUNDERstorm that points out the ground-breaking Roar of this project. It aims to detect novel thunderstorm measurements, to create a huge dataset of field acquisitions and a new interpretation of their weather scenarios, to conduct unique wind tunnel tests and CFD analyses, to formulate a thunderstorm model that is physically correct and suitable to develop a loading scheme easily transferable to engineering and codification, to radically change the existing wind loading format and the engineering practice, to design safer and cost-efficient structures producing a deep social and economic impact.
[ "Products and Processes Engineering", "Earth System Science" ]
10.1002/ijc.29841
Diverse expression patterns of the EMT suppressor grainyhead-like 2 (GRHL2) in normal and tumour tissues
The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes. Although GRHL2 recently has attracted considerable interest in that it could be identified as a novel suppressor of the epithelial-to-mesenchymal transition, evidence is emerging that GRHL2 also exhibits tumour-promoting activities. Aim of the present study therefore was to help defining the relevance of GRHL2 for human cancers by performing a comprehensive immunohistochemical analysis of GRHL2 expression in normal (n = 608) and (n = 3,143) tumour tissues using tissue microarrays. Consistent with its accepted role in epithelial morphogenesis, GRHL2 expression preferentially but not exclusively was observed in epithelial cells. Regenerative and proliferating epithelial cells with stem cell features showed a strong GRHL2 expression. Highly complex GRHL2 expression patterns indicative of both reduced and elevated GRHL2 expression in tumours, possibly reflecting potential tumour-suppressing as well as oncogenic functions of GRHL2 in distinct human tumours, were observed. A dysregulation of GRHL2 expression for the first time was found in tumours of non-epithelial origin (e. g. , astrocytomas, melanomas). We also report GRHL2 copy number gains which, however, did not necessarily translate into increased GRHL2 expression levels in cancer cells. Results obtained by meta-analysis of gene expression microarray data in conjunction with functional assays demonstrating a direct regulation of HER3 expression further point to a potential therapeutic relevance of GRHL2 in ovarian cancer. Hopefully, the results presented in this study may pave the way for a better understanding of the yet largely unknown function of GRHL2 in the initiation, progression and also therapy of cancers. What's new? Transcription factor "grainyhead-like 2" (GRHL2) acts as a tumour suppressor in breast cancer, but it may have tumour-promoting activities in other cancers. In this study using immunohistochemistry and tissue microarrays, the authors found that GRHL2 expression is dysregulated in a broad range of malignant tumours, including astrocytoma, melanoma, breast and ovarian cancers. These results indicate that GRHL2 may offer a potential therapeutic target, and further studies should enhance our understanding of its role in numerous types of cancer.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1038/nature14665
Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity
Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumours that are classified into different histological and molecular subtypes. PIK3CA and P53 (also known as TP53) are the two most frequently mutated genes and are associated with different types of human breast cancers. The cellular origin and the mechanisms leading to PIK3CA-induced tumour heterogeneity remain unknown. Here we used a genetic approach in mice to define the cellular origin of Pik3ca-derived tumours and the impact of mutations in this gene on tumour heterogeneity. Surprisingly, oncogenic Pik3caH1047R mutant expression at physiological levels in basal cells using keratin (K)5-CreERT2 mice induced the formation of luminal oestrogen receptor (ER)-positive/progesterone receptor (PR)-positive tumours, while its expression in luminal cells using K8-CReERT2 mice gave rise to luminal ER+ PR+ tumours or basal-like ER- PR- tumours. Concomitant deletion of p53 and expression of Pik3caH1047R accelerated tumour development and induced more aggressive mammary tumours. Interestingly, expression of Pik3caH1047R in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumours. Transcriptional profiling of cells that underwent cell fate transition upon Pik3caH1047R expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3caH1047R expression in basal and luminal cells, which correlated with the cell of origin, tumour type and different clinical outcomes. Altogether our study identifies the cellular origin of Pik3ca-induced tumours and reveals that oncogenic Pik3caH1047R activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumour initiation, setting the stage for future intratumoural heterogeneity. These results have important implications for our understanding of the mechanisms controlling tumour heterogeneity and the development of new strategies to block PIK3CA breast cancer initiation.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1002/eji.201646756
NK-cell receptors NKp46 and NCR1 control human metapneumovirus infection
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46-activating receptor and its mouse orthologue Ncr1, both members of the natural cytotoxicity receptor (NCR) family, recognized an unknown ligand expressed by HMPV-infected human cells. We demonstrated that MHC class I is upregulated and MICA is downregulated upon HMPV infection. We also characterized mouse NK-cell phenotype in the blood and the lungs of HMPV-infected mice and found that lung NK cells are more activated and expressing NKG2D, CD43, CD27, KLRG1, and CD69 compared to blood NK cells regardless of HMPV infection. Finally, we demonstrated, using Ncr1-deficient mice, that NCR1 plays a critical role in controlling HMPV infection.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1021/acs.jpclett.7b00784
Accurate Neural Network Description of Surface Phonons in Reactive Gas-Surface Dynamics: N<inf>2</inf> + Ru(0001)
Ab initio molecular dynamics (AIMD) simulations enable the accurate description of reactive molecule-surface scattering especially if energy transfer involving surface phonons is important. However, presently, the computational expense of AIMD rules out its application to systems where reaction probabilities are smaller than about 1%. Here we show that this problem can be overcome by a high-dimensional neural network fit of the molecule-surface interaction potential, which also incorporates the dependence on phonons by taking into account all degrees of freedom of the surface explicitly. As shown for N2 + Ru(0001), which is a prototypical case for highly activated dissociative chemisorption, the method allows an accurate description of the coupling of molecular and surface atom motion and accurately accounts for vibrational properties of the employed slab model of Ru(0001). The neural network potential allows reaction probabilities as low as 10-5 to be computed, showing good agreement with experimental results.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]