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W2065748344 | The Age Profile of the Income–Health Gradient: An Evaluation of Two Large Cohorts of Contemporary US Children | The purpose of this study was to evaluate the dynamics of health and income in contemporary US children and the influence of these dynamics on the age profile of an income–health gradient. Two large cohorts were used to evaluate income gradients in children from 9 months to 5 years and from 6 to 14 years using dynamic specifications of random effects models. An income gradient in parental reports of poor child health was observed in two large cohorts of contemporary US children with ages ranging from infancy to early adolescence. When estimated in separate models both current and averaged income exhibited steepening gradients over the ages of both samples. When estimated jointly only current income exhibited a steepening gradient. While state dependence in health was indicated in dynamic models it did not influence the magnitude or age profile of the income effects. The findings suggested that the age profile of an income–health gradient in the health of US children may depend on whether income is measured as a long-term or short-term variable. Distinguishing these patterns is important for an understanding of how families cope with their children’s health adversities. | [
"Physiology in Health, Disease and Ageing",
"Individuals, Markets and Organisations",
"The Social World and Its Interactions"
]
|
10.1090/S0002-9947-2014-05884-4 | The Brezis Nirenberg Result For The Fractional Laplacian | The aim of this paper is to deal with the non-local fractional counterpart of the Laplace equation involving critical non-linearities studied in the famous paper of Brezis and Nirenberg (1983). Namely, our model is the equation { (−Δ)su− λu = |u|2−2u in Ω, u = 0 in Rn \ Ω , where (−Δ)s is the fractional Laplace operator, s ∈ (0, 1), Ω is an open bounded set of Rn, n > 2s, with Lipschitz boundary, λ > 0 is a real parameter and 2∗ = 2n/(n− 2s) is a fractional critical Sobolev exponent. In this paper we first study the problem in a general framework; indeed we consider the equation { LKu+ λu+ |u|2 −2u+ f(x, u) = 0 in Ω, u = 0 in Rn \ Ω , where LK is a general non-local integrodifferential operator of order s and f is a lower order perturbation of the critical power |u|2−2u. In this setting we prove an existence result through variational techniques. Then, as a concrete example, we derive a Brezis-Nirenberg type result for our model equation; that is, we show that if λ1,s is the first eigenvalue of the non-local operator (−Δ)s with homogeneous Dirichlet boundary datum, then for any λ ∈ (0, λ1,s) there exists a non-trivial solution of the above model equation, provided n 4s. In this sense the present work may be seen as the extension of the classical Brezis-Nirenberg result to the case of non-local fractional operators. | [
"Mathematics"
]
|
340055 | Metal catalysis in biological habitats: New strategies for optical bio-sensing and targeted therapy | This proposal aims at the discovery of robust transition-metal catalyzed transformations that can take place in aqueous media and cellular lysates, and are susceptible of being exported to living cells. Specifically, we will exploit the special coordination and activation ability of different metal complexes towards pi-systems to induce chemo-selective reactions of designed, abiotic, unsaturated substrates. Moreover, and importantly, the metal catalysts will be conjugated to designed ligands or biopolymers so that the catalytic power of the metal complex can be transferred to specific “in vivo” locations. Initial designs in this latter “high risk” endeavor will be guided by the current knowledge on metal-catalyzed bio-orthogonal chemistry as well as by some precedents on catalysis-based metal-sensing tactics.
Ultimately, we want to install catalytic power in specific cellular sites and/or endow catalytic properties to any selected bio-molecular target. The catalytic activity could then be used to trigger the amplified generation of fluorescent signals or boost the production of bioactive drugs from inert, non-toxic precursors. This will set the basis for the development of efficient bio-sensing and imaging tools, and “in cellulo” diagnosis tactics, and of novel target-directed therapeutic strategies. With the crescent identification of disease-related biomarkers, the development of biomarker-associated diagnosis and therapy protocols is becoming one of the more urgent challenges in modern life sciences. Advances in early diagnosis can have a profound impact in public health, and boost new technology developments.
The transversal expertise of my group in synthesis, metal catalysis, molecular recognition and chemical biology (see PI profile) places us in a rather unique position to tackle this type of interdisciplinary project. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
US 201414492582 A | ISOLATION SCHEME FOR BIPOLAR TRANSISTORS IN BICMOS TECHNOLOGY | Device structures and design structures for a bipolar junction transistor. The device structure includes a collector region in a substrate, a plurality of isolation structures extending into the substrate and comprised of an electrical insulator, and an isolation region in the substrate. The isolation structures have a length and are arranged with a pitch transverse to the length such that each adjacent pair of the isolation structures is separated by a respective section of the substrate. The isolation region is laterally separated from at least one of the isolation structures by a first portion of the collector region. The isolation region laterally separates a second portion of the collector region from the first portion of the collector region. The device structure further includes an intrinsic base on the second portion of the collector region and an emitter on the intrinsic base. The emitter has a length transversely oriented relative to the length of the isolation structures. | [
"Systems and Communication Engineering",
"Materials Engineering"
]
|
215551 | Cognitively enhanced robot for flexible manufacturing of metal and composite parts | COROMA project proposes to develop a cognitively enhanced robot that can execute multiple tasks for the manufacturing of metal and composite parts. COROMA will therefore provide the flexibility that European metalworking and advanced material manufacturing companies require to compete in the rapidly evolving global market.
The main output of COROMA project will be a modular robotic system that will perform multitude of different manufacturing tasks in an autonomous way to adapt to the production requirements. The robot will be capable of performing drilling, trimming, deburring, polishing, sanding, non-destructive inspection and adaptive fixturing operations. Using a simple interface the robot will receive basic commands that require a minimum programming effort from the human operator. The robot will autonomously navigate in the workshop and will automatically perceive the manufacturing scene and locate the part that must be manufactured and even handle some of the required tools. Learning from previous experiences during displacement, tool grasping, part localisation and the manufacturing process itself, the robot will improve its performance. It will be able to interact with other machines in the shop floor and to work on a part even while other manufacturing operations are being performed by these other machines. Safe human-robot and machine-robot collaborations will be paramount and the robot will automatically react to the presence of both humans and other machines. The modularity of the COROMA robot will permit to customize it to meet specific requirements from different manufacturing companies.
These challenges require a project consortium where the latest robotic technologies meet knowledge from manufacturing experts, including both industry and academia. COROMA project consortium presents a perfect balance between manufacturing and robotics sectors' players. | [
"Products and Processes Engineering",
"Computer Science and Informatics",
"Materials Engineering"
]
|
W1988974519 | The Relationship Between the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Olfaction in Patients Referred for a Dementia Evaluation | The current study examined the relationship between a standardized dementia battery (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]) and a test of olfactory discrimination (University of Pennsylvania Smell Identification Test [UPSIT]) in a heterogeneous sample of patients referred for a dementia assessment (N = 103). Significant moderate correlations were found between the UPSIT and each of the RBANS indexes, with the strongest correlation for Total Scale score, followed by the Delayed Memory Index and the Language Index. Significant moderate correlations were also found between the UPSIT and 11 of the 12 subtests of the RBANS. While the major RBANS indexes demonstrated significant correlations with education and the Wechsler Test of Adult Reading, a measure of premorbid IQ, the UPSIT did not. This suggests the UPSIT may be sensitive to decline in dementia and largely unaffected by premorbid cognitive functioning. As a result, the UPSIT may provide neuropsychologists with an efficient, cost-effective, and sensitive supplement to a standard dementia battery. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
]
|
10.1039/C4DT00152D | Reactivity And Catalytic Activity Of Tert Butoxy Aluminium Hydride Reagents | The reactivity and catalytic activities of the tert-butoxy aluminium hydride reagents [(tBuO)xAlH3−x] [x = 1 (1), 2 (2)] and (L)Li[(tBuO)2AlH2] [L = THF (3), 1,4-dioxane (4)] are investigated. The structural characterisation of the novel compounds 3 and 4 shows that the nature of the hydridic species present is affected dramatically by the donor ligand coordinating the Li+ cation. Stoichiometric reaction of 1 with pyridine gives [(1,4-H-pyrid-1-yl)4Al]−[(pyridine)4AlH2]+ (5) while reaction with the amine–borane Me2NHBH3 in the presence of PMDETA [(Me2NCH2CH2)2NMe] affords [(PMDETA)AlH2]+[(BH3)2NMe2]− (6). The reagents 1–4 catalyse the dehydrocoupling reaction of the amine–borane Me2NHBH3 into the ring compound [Me2NBH2]2, with the activity decreasing in the order 1 ≫ 2 ∼ 3 > 4. The greater reactivity of the neutral dihydride 1 provides the potential basis for future catalytic optimisation. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1016/j.bbabio.2015.04.001 | Functional characteristics of spirilloxanthin and keto-bearing Analogues in light-harvesting LH2 complexes from Rhodobacter sphaeroides with a genetically modified carotenoid synthesis pathway | Light-harvesting 2 (LH2) complexes from a genetically modified strain of the purple photosynthetic bacterium Rhodobacter (Rba. ) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. Carotenoid synthesis in the Rba. sphaeroides strain was engineered to redirect carotenoid production away from spheroidene into the spirilloxanthin synthesis pathway. The strain assembles LH2 antennas with substantial amounts of spirilloxanthin (total double-bond conjugation length N = 13) if grown anaerobically and of keto-bearing long-chain analogs [2-ketoanhydrorhodovibrin (N = 13), 2-ketospirilloxanthin (N = 14) and 2,2′-diketospirilloxanthin (N = 15)] if grown semi-aerobically (with ratios that depend on growth conditions). We present the photophysical, electronic, and vibrational properties of these carotenoids, both isolated in organic media and assembled within LH2 complexes. Measurements of excited-state energy transfer to the array of excitonically coupled bacteriochlorophyll a molecules (B850) show that the mean lifetime of the first singlet excited state (S<inf>1</inf>) of the long-chain (N ≥ 13) carotenoids does not change appreciably between organic media and the protein environment. In each case, the S<inf>1</inf> state appears to lie lower in energy than that of B850. The energy-transfer yield is ∼ 0. 4 in LH2 (from the strain grown aerobically or semi-aerobically), which is less than half that achieved for LH2 that contains short-chain (N ≤ 11) analogues. Collectively, the results suggest that the S<inf>1</inf> excited state of the long-chain (N ≥ 13) carotenoids participates little if at all in carotenoid-to-BChl a energy transfer, which occurs predominantly via the carotenoid S<inf>2</inf> excited state in these antennas. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
10.1117/12.2311706 | The Mirc X 6 Telescope Imager Key Science Drivers Instrument Design And Operation | MIRC-X is a new beam combination instrument at the CHARA array that enables 6-telescope interferometric imaging on object classes that until now have been out of reach for milliarcsecond-resolution imaging. As part of an instrumentation effort lead by the University of Exeter and University of Michigan, we equipped the MIRC instrument with an ultra-low read-noise detector system and extended the wavelength range to the J and H- band. The first phase of the MIRC-X commissioning was successfully completed in June 2017. In 2018 we will commission polarisation control to improve the visibility calibration and implement a 'cross-talk resiliant' mode that will minimise visibility cross-talk and enable exoplanet searches using precision closure phases. Here we outline our key science drivers and give an overview about our commissioning timeline. We comment on operational aspects, such as remote observing, and the prospects of co-phased parallel operations with the upcoming MYSTIC combiner. | [
"Universe Sciences",
"Systems and Communication Engineering"
]
|
10.1080/19491034.2017.1292192 | Choreography of parental histones in damaged chromatin | In the cell nucleus, DNA repair machineries operate on a chromatin substrate, whose integrity is key for preserving cell functions and identity. Yet, it is still unclear how the epigenetic information conveyed by chromatin is maintained during the DNA repair process. We recently characterized the dynamics of parental histones coupled to UV-C damage repair in human cells, providing insights into how the pre-damage chromatin state may be restored. Here, we summarize our main findings and discuss them in the context of epigenome maintenance following DNA damage. We further address the mechanistic aspects of repair-coupled histone dynamics and develop working hypotheses regarding their functional relevance in the cellular response to genotoxic stress. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
10.1021/ja200310d | Water ordering at membrane interfaces controls fusion dynamics | Membrane interfaces are critical to many cellular functions, yet the vast array of molecular components involved make the fundamental physics of interaction difficult to define. Water has been shown to play an important role in the dynamics of small biological systems, for example when trapped in hydrophobic regions, but the molecular details of water have generally been thought dispensable when considering large membrane interfaces. Nevertheless, spectroscopic data indicate that water has distinct, ordered behavior near membrane surfaces. While coarse-grained simulations have achieved success recently in aiding understanding the dynamics of membrane assemblies, it is natural to ask, does the missing chemical nature of water play an important role? We have therefore performed atomic-resolution simulations of vesicle fusion to understand the role of chemical detail, particularly the molecular structure of water, in membrane fusion and at membrane interfaces more generally. These membrane interfaces present a form of hydrophilic confinement, yielding surprising, non-bulk-like water behavior. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
W44134350 | Electricity Markets and Pricing for the Distributed Generation Era | Wholesale and retail electricity markets have changed little over the past century, with flat kilowatt-hour pricing still the norm. This outdated model will have to change to meet the future challenges facing the industry. Present market structures are ill-adapted to the cost and operating characteristics of a decarbonized supply side, especially in view of technological innovations in distributed energy resources. The prices that energy markets produce do not underpin investment in these sources or give useful operating signals for intermittent sources like wind and solar. Meanwhile, consumers are either sheltered from the impact of wholesale market volatility or faced with confusing and perverse price signals. The chapter considers various options for a pricing structure linking supply and demand coherently, including a reconceptualization of electricity into two products: “as-available” and “on-demand” power. The implications of these developments for electricity business models and investment are examined. | [
"Individuals, Markets and Organisations",
"Products and Processes Engineering"
]
|
Q4756582 | KONSOLIDIERUNG DER BEREITS ERWORBENEN AUSLANDSMÄRKTE UND START NEUER KOMMERZIELLER KOOPERATIONEN ZUR EINFÜHRUNG NEUER PRODUKTE FÜR NEUE LÄNDER UND MÄRKTE. | KONSOLIDIERUNG DER BEREITS ERWORBENEN AUSLANDSMÄRKTE UND START NEUER KOMMERZIELLER KOOPERATIONEN ZUR EINFÜHRUNG NEUER PRODUKTE FÜR NEUE LÄNDER UND MÄRKTE. | [
"Individuals, Markets and Organisations"
]
|
10.1155/2016/8543475 | External Quantum Efficiency Improvement With Luminescent Downshifting Layers Experimental And Modelling | Core-shell quantum dots CdSe/ZnS and lumogen yellow organic dye are characterized by their inclusion in luminescent downshifting (LDS) layers. Layers were deposited on top of crystalline silicon cell (c-Si), dye synthesized solar cell (DSSC), and cadmium telluride (CdTe) minimodules. External quantum efficiency measurements for the solar cell/LDS devices are discussed. Experimental results were compared with an optical model developed by Rothemund, 2014. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Materials Engineering"
]
|
10.1063/1.4813517 | Spatial Distribution Of Neutral Oxygen Vacancies On Zno Nanowire Surfaces An Investigation Combining Confocal Microscopy And First Principles Calculations | mechanism behind the green emission spectral intensity and the characteristics of an individual ZnO NW. The highly accurate density functional theory (DFT)-based full-potential linearized augmented plane-wave plus local orbitals (FP-LAPW þ lo) method is used to compute the defect formation energy (DFE) of the SSs. Previously, using these SS models, it was demonstrated through the FP-LAPW + lo method that in the presence of oxygen vacancies at the (0001) surface, the phase transformation of the SSs in the graphite-like structure to the wurtzite lattice structure will occur even if the thickness of the graphite-like SSs are equal to or less than 4 atomic graphite-like layers [Wong et al. , J. Appl. Phys. 113, 014304 (2013)]. The spatial profile of the neutral VO DFEs from the DFT calculations along the ZnO [0001] and [10 � directions is found to reasonably explain the spatial profile of the measured confocal luminescence intensity on these surfaces, leading to the conclusion that the green emission spectra of the NWs likely originate from neutral oxygen vacancies. Another significant result is that the variation in the calculated DFE along the ZnO [0001] and [10 � directions shows different behaviors owing to the non-polar and polar nature of these SSs. These results are important for tuning and understanding the variations in the optical response of ZnO NW-based devices in different geometric configurations. V C 2013 Author(s). All article | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
W2069420808 | SU-F-BRA-04: Automatic Bladder Segmentation on CBCT for Online ART of Bladder Cancer | Purpose: Large day-to-day variations in bladder—filling hamper accurate radiotherapy of bladder cancer. To allow accurate ART for bladder cancer, automatic bladder segmentation in CBCT is required. However, image quality limitations make this a challenging task. Our aim is to develop an automatic bladder segmentation method using spherical harmonics. Methods: The method includes two steps: a statistical bladder model was built from training dataset (98 bladder contours from 8 patients) and this model was then applied to automatic bladder segmentation in an independent test dataset (110 CBCT scans from another 7 patients). 3D bladder contours were converted into parametric surface descriptions using spherical harmonic expansion. Principle component analysis (PCA) was applied in the spherical harmonic based shape parameter space to calculate the major variations of bladder shape. The number of PCA modes was chosen such that 90% variation in the training dataset was described. By changing the weight of each PCA mode, an initial contour (from the first CBCT of each patient) was deformed to obtain the best fit with the bladder edge in test image. The fit was achieved by optimizing a cost function based on the image gradient using a simplex optimizer. Results: Only 5 PCA modes were needed to represent 90% of the bladder shape variation. The mean and SD of the absolute residual error over all test dataset were 4.8mm and 3.5mm, respectively. The mean volume overlap was 76%. The agreement of plan selection between automatic and manual bladder segmentation was 71%, which was similar to human observer. Conclusions: PCA on spherical harmonics space efficiently describes bladder deformation. This segmentation approach is robust to relatively poor CBCT image quality and allows fast and automatic segmentation of bladder on CBCT with moderate accuracy. This method can potentially be used to select the appropriate plan for online ART of bladder cancer. The research was funded by Dutch Cancer Society. No conflict of interest. | [
"Computer Science and Informatics",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Products and Processes Engineering"
]
|
2720187 | A novel non-invasive solution for continuous blood pressure monitoring | Blood pressure follow-up is essential in managing hemodynamically unstable patients at Intensive Care Units (ICU). Traditionally, mercury sphygmomanometers have been used for this purpose, and are regarded as the gold standard for Blood Pressure measurement. Despite the relative simplicity of the technique, sphygmomanometers have obvious limitations regarding accuracy and tracking capability, especially crucial for hospital patients. In the most critical patients the invasive arterial line catheter must be used, which however poses serious risks for severe complications.
Over the past decades, several attempts have been undertaken to develop an effective, accurate and reliable solutions to continuously monitor blood pressure in a non-invasive way. Hitherto, none of the solutions under development have achieved a massive market deployment. Major obstacles for the implementation of state-of-the-art solutions are related to their limited performance, resulting in poor accuracy in hypo/hyper tension episodes, influence of patient movements on the system response, and need for periodic and frequent recalibrations.
ICARIA has developed a solution for blood pressure monitoring (ICA-100) based on a novel operating principle that allows obtaining an accurate diastolic and systolic Blood Pressure read-out. The ICA-100 has already been validated in healthy volunteers (TRL5). The technology is protected by two international patents, granting ICARIA freedom-to-operate.
In the frame of this Phase 1 Project we aim to further develop our marketing strategy and financial plan. Besides, we aim to assess thoroughly the relevant regulatory and legal framework for the Project. After completing this feasibility study, we plan to develop and commercialise a certified device for Continuous Non-Invasive Blood Pressure monitoring. Having a positive impact in 655m hospital patients and a potential favourable effect on 1.3b hypertensive individuals, from which only 1 in 5 is under control. | [
"Products and Processes Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
W1492322020 | Structure and magnetic properties of bulk nanocrystalline Tm2(Co1−xFex)17 permanent magnet | Structure and magnetic properties were studied for Tm2(Co1−xFex)17 bulk nanocrystalline magnet synthesized by spark plasma sintering technique. X-ray diffraction results indicate both ingot and sintered magnet of Tm2(Co0.7Fe0.3)17 alloy exhibit hexagonal Th2Ni17 type structure. The microstructure of the magnet is composed of Th2Ni17 type nanograins with an average size of 35 nm detected by transmission electron microscopy and selected area electron diffraction patterns. Magnetic measurement shows that the remanence of the magnet is higher at 573 K than at 300 K, indicating there is a positive remanence temperature coefficient in the magnet. The anisotropy field of Tm2(Co0.7Fe0.3)17 alloy is 3.8 T, which is much higher than the HA of 2.3 T for the pure Tm2Co17 alloy. The coercivity of the sintered magnet increases from 0.25 to 0.354 T after optimal annealing. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1002/hep.27028 | The COP9 signalosome is a repressor of replicative stress responses and polyploidization in the regenerating liver | Aberrant DNA replication induced by deregulated or excessive proliferative stimuli evokes a "replicative stress response" leading to cell cycle restriction and/or apoptosis. This robust fail-safe mechanism is eventually bypassed by transformed cells, due to ill-defined epistatic interactions. The COP9 signalosome (CSN) is an evolutionarily conserved regulator of cullin ring ligases (CRLs), the largest family of ubiquitin ligases in metazoans. Conditional inactivation of the CSN in several tissues leads to activation of S- or G2-phase checkpoints resulting in irreversible cell cycle arrest and cell death. Herein we ablated COPS5, the CSNs catalytic subunit, in the liver, to investigate its role in cell cycle reentry by differentiated hepatocytes. Lack of COPS5 in regenerating livers causes substantial replicative stress, which triggers a CDKN2A-dependent genetic program leading to cell cycle arrest, polyploidy, and apoptosis. These outcomes are phenocopied by acute overexpression of c-Myc in COPS5 null hepatocytes of adult mice. Conclusion: We propose that combined control of proto-oncogene product levels and proteins involved in DNA replication origin licensing may explain the deleterious consequences of CSN inactivation in regenerating livers and provide insight into the pathogenic role of the frequently observed overexpression of the CSN in hepatocellular carcinoma. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
714551 | Defining the role of the FGF – autophagy axis in bone physiology | Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
10.1051/0004-6361/201731636 | Properties Of Quasi Periodic Pulsations In Solar Flares From A Single Active Region | We investigate the properties of a set of solar flares originating from a single active region (AR) that exhibit QPPs, and look for signs of the QPP periods relating to AR properties. The AR studied, best known as NOAA 12192, was unusually long-lived and produced 181 flares. Data from the GOES, EVE, Fermi, Vernov and NoRH observatories were used to determine if QPPs were present in the flares. For the soft X-ray GOES and EVE data, the time derivative of the signal was used. Power spectra of the time series data (without any form of detrending) were inspected, and flares with a peak above the 95% confidence level in the spectrum were labelled as having candidate QPPs. The confidence levels were determined taking account of uncertainties and the possible presence of red noise. AR properties were determined using HMI line of sight magnetograms. A total of 37 flares (20% of the sample) show good evidence of having QPPs, and some of the pulsations can be seen in data from multiple instruments and in different wavebands. The QPP periods show a weak correlation with the flare amplitude and duration, but this may be due to an observational bias. A stronger correlation was found between the QPP period and duration of the QPP signal, which can be partially but not entirely explained by observational constraints. No correlations were found with the AR area, bipole separation, or average magnetic field strength. The fact that a substantial fraction of the flare sample showed evidence of QPPs using a strict detection method with minimal processing of the data demonstrates that these QPPs are a real phenomenon, which cannot be explained by the presence of red noise or the superposition of multiple unrelated flares. The lack of correlation between the QPP periods and AR properties implies that the small-scale structure of the AR is important, and/or that different QPP mechanisms act in different cases. | [
"Universe Sciences"
]
|
10.1523/JNEUROSCI.1213-17.2017 | Visual Experience Shapes The Neural Networks Remapping Touch Into External Space | Localizing touch relies on the activation of skin-based and externally defined spatial frames of reference. Psychophysical studies have demonstrated that early visual deprivation prevents the automatic remapping of touch into external space. We used fMRI to characterize how visual experience impacts the brain circuits dedicated to the spatial processing of touch. Sighted and congenitally blind humans performed a tactile temporal order judgment (TOJ) task, either with the hands uncrossed or crossed over the body midline. Behavioral data confirmed that crossing the hands has a detrimental effect on TOJ judgments in sighted but not in early blind people. Crucially, the crossed hand posture elicited enhanced activity, when compared with the uncrossed posture, in a frontoparietal network in the sighted group only. Psychophysiological interaction analysis revealed, however, that the congenitally blind showed enhanced functional connectivity between parietal and frontal regions in the crossed versus uncrossed hand postures. Our results demonstrate that visual experience scaffolds the neural implementation of the location of touch in space. SIGNIFICANCE STATEMENT In daily life, we seamlessly localize touch in external space for action planning toward a stimulus making contact with the body. For efficient sensorimotor integration, the brain has therefore to compute the current position of our limbs in the external world. In the present study, we demonstrate that early visual deprivation alters the brain activity in a dorsal parietofrontal network typically supporting touch localization in the sighted. Our results therefore conclusively demonstrate the intrinsic role that developmental vision plays in scaffolding the neural implementation of touch perception. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
]
|
Q81734 | Obtaining patent protection for dual-fuel direct-injection engines | Reference number of the aid programme: SA.42799(2015/X), intended for public aid: Article 28 of Commission Regulation No 651/2014 This proposal focuses on obtaining industrial property protection in the form of a patent for a dual-fuel system for direct fuel injection engines. Generally known LPG fuelling systems are not effective in FSI engines, TSIs, due to the lack of cooling of petrol injectors. To prevent this, additional gasoline injection is used when operating on gas, which significantly reduces the economy of gas engines. In addition, adding additional gas phase injectors in front of the engine suction valves, causes a number of technical problems and causes high CPU conversion power to mimic the correct engine operation. These defects are deprived of the technical solution of Kael, which has been reported as an invention in Poland. The solution according to the invention means that there is no need to add additional alternative fuel injectors, and the liquid-phase gas flowing through petrol injectors does not change the working conditions of the gas. All engine operating parameters are similar to petrol, the economy of this solution is much higher, and exhaust gas tests indicate an increase in ecological parameters. The implementation of this project will allow to examine the current state of technology in terms of solutions similar to the subject of the project, examination of capabilities in the international procedure of PCT, costs related to legal services in the field of industrial protection, costs of patent attorneys, costs of advisory services preparing for the commercialisation process, preparation of translations and official fees. As a result of the project, Kael will protect itself against the appearance of competing circuits. | [
"Products and Processes Engineering"
]
|
W2331317313 | Equivalent waveband selection of VIS-NIR spectroscopic measurement for hemoglobin | The VIS-NIR spectroscopy combined with the improved Moving Window Partial Least-square(MWPLS) method was applied to a high accurate waveband selection for the rapid no-reagent determination of Hemoglobin(HGB) in human whole blood.A new modeling evaluation system was proposed to avoid the evaluation distortion.First,seventy samples were randomly selected from a total of 205 samples as the validation set,the remaining 135 samples were used as the modeling set,and the modeling set was divided into similar calibration(80 samples) and prediction(55 samples) sets for a total of 50 times.Then,modeling and optimization were performed in each division to get stable model.Finally,the optimized model was validated again using the validation set.Experimental results indicate that the VIS-short NIR region 400-1 100 nm can be used as the information waveband of HGB in human whole blood,the global optimal waveband 492-890 nm is further selected from 400-1100 nm with MWPLS method,and a model space including 77 equivalent wavebands is obtained.By taking the 492-890 nm for an example,validation effects V-SEP,V-RP,and V-RSEP are 2.58 g L-1,0.988,and 1.97%,respectively.It concludes that HGB prediction values of the samples are highly close to the clinic measured values,which may be used in clinical diagnosis. | [
"Physical and Analytical Chemical Sciences",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
978299 | Study of tau strains to understand the phenotypic diversity of alzheimer’s disease: a step toward personalized therapies | Dementia represents a major challenge for our ageing societies. The number of citizens suffering from dementia in the EU is expected to reach 19 millions by 2050. Alzheimer’s disease (AD) is responsible for the vast majority of dementia cases. However there is still not a single available treatment that modifies the course of disease. Therefore, the development of innovative approaches to better understand the pathophysiology and ultimately treat patients must be a priority. This project aims to understand the determinants of the diversity of AD clinical phenotypes through the deep analysis of pathological variants of the tau protein. As the accumulation of Aβ peptide has long been considered a causative event in AD, most therapeutic approaches have targeted Aβ metabolism, but unsuccessfully. Modern biomarkers, have confirmed that the brain deposition of tau pathology, the other hallmark of AD, correlates much better with human cognition and neurodegeneration. Recently, it was shown that tau behaves like a prion and can spread from one neuron to another. Moreover, tau strains or conformers seem to template native tau and propagate the pathological conformation with high fidelity. Discrete tau strains generate distinct aggregates morphology or patterns of neuronal vulnerability. I postulate that different strains of tau are responsible for the variability of AD and may determine the progression rate, gender differences or clinical expression. Therefore, my objective is to develop the technologies to identify tau strains signatures in distinct AD phenotypes. In particular, I plan to develop and optimize biosensor cell lines that sensitively detect tau strains from human brain samples and cerebrospinal fluid, and characterize respective repertoire of tau strains. Understanding AD heterogeneity would potentially increase our ability to take care of every individual patient. In addition, this work could lead to the development of biomarkers and novel targeted therapies. | [
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2529576091 | PMML in Action: Unleashing the Power of Open Standards for Data Mining and Predictive Analytics | The data mining community has derived a broad foundation of statistical algorithms and software solutions that has allowed predictive analytics to become a standard approach used in science and industry.For many years, much emphasis has been placed on the development of predictive models. As a consequence, the market place offers a range of powerful tools, many open-source, for effective model building. However, once we turn to the operational deployment and practical application of predictive solutions within an existing IT infrastructure, we face a much more limited choice of options. Often it takes months for models to be integrated and deployed via custom code or proprietary processes.The Predictive Model Markup Language (PMML) standard has reached a significant stage of maturity and has obtained broad industry support, allowing users to develop predictive solutions within one application and use another to execute them. Previously, this was very difficult, but with PMML, the exchange of predictive solutions between compliant applications is now straightforward.The aim of this book is to present PMML from a practical perspective. It contains a variety of code snippets so that concepts are made clear through the use of examples. Readers are assumed to have a basic knowledge of predictive analytics and its techniques and so the book is intended for data mining movers and shakers: anyone interested in moving predictive analytic solutions between applications, including students and scientists.PMML in Action is a great way to learn how to represent your predictive solutions through a mature and refined open standard. For the 2nd edition, the book has been completely revised for PMML 4.1, the latest version of PMML. It includes new chapters and an expanded description of how to represent multiple models in PMML, including model ensemble, segmentation, chaining, and composition. The book is divided into six parts, taking you in a PMML journey in which language elements and attributes are used to represent not only modeling techniques but also data pre- and post-processing.With PMML, users benefit from a single and concise standard to represent predictive models, thus avoiding the need for custom code and proprietary solutions.You too can join the PMML movement! Unleash the power of predictive analytics and data mining today | [
"Computer Science and Informatics",
"Mathematics"
]
|
10.1016/j.astropartphys.2019.04.007 | Estimation of radio emission from neutrino induced showers in rock salt above 10<sup>18</sup> eV | Emission of electromagnetic waves from high energy particle showers is a powerful tool that can be used to detect the most elusive cosmic neutrinos of astrophysical or cosmogenic origin. We present here simulations of showers with a primary energy in the range 1018−1021 eV initiated by νe, νμ and ντ neutrinos. A medium that is both dense and transparent in the low radio frequencies part of the electromagnetic spectrum, like rock salt, is used as active medium where the shower develops. The calculation of the radio signal was performed by approximating the shower with a current density using the longitudinal profile of the charge excess, for estimation at low frequencies, below 500 MHz. The aim of this work is to give estimates of the amplitude of the signal induced by νe, νμ and ντ neutrinos. | [
"Fundamental Constituents of Matter",
"Universe Sciences"
]
|
10.1080/13527258.2019.1663235 | Politics Of Solidarity In The Context Of European Heritage The Cases Of The European Solidarity Centre And Hambach Castle | This article explores the politics of solidarity in the framework of constructing a common cultural heritage of the European Union. The politics of solidarity stems from the notion of solidarity em. . . | [
"Institutions, Governance and Legal Systems",
"Studies of Cultures and Arts"
]
|
10.1016/j.celrep.2016.05.085 | Neutrophil-Derived IL-1β Impairs the Efficacy of NF-κB Inhibitors against Lung Cancer | Although epithelial NF-κB signaling is important for lung carcinogenesis, NF-κB inhibitors are ineffective for cancer treatment. To explain this paradox, we studied mice with genetic deletion of IKKβ in myeloid cells and found enhanced tumorigenesis in KrasG12D and urethane models of lung cancer. Myeloid-specific inhibition of NF-κB augmented pro-IL-1β processing by cathepsin G in neutrophils, leading to increased IL-1β and enhanced epithelial cell proliferation. Combined treatment with bortezomib, a proteasome inhibitor that blocks NF-κB activation, and IL-1 receptor antagonist reduced tumor formation and growth in vivo. In lung cancer patients, plasma IL-1β levels correlated with poor prognosis, and IL-1β increased following bortezomib treatment. Together, our studies elucidate an important role for neutrophils and IL-1β in lung carcinogenesis and resistance to NF-κB inhibitors. | [
"Immunity, Infection and Immunotherapy",
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1039/C5MT00286A | Natural Hg Isotopic Composition Of Different Hg Compounds In Mammal Tissues As A Proxy For In Vivo Breakdown Of Toxic Methylmercury | In the last decade, specific attention has been paid to total mercury (HgT) stable isotopic composition, especially in natural samples such as aquatic organisms, due to its potential to track the cycle of this toxic element in the environment. Here, we investigated Hg Compound Specific stable Isotopic Composition (CSIC) of natural inorganic Hg (iHg) and methylmercury (MMHg) in various tissues of aquatic mammals (Beluga whale from the Arctic marine environment and seals from the freshwater lake Baikal, Russia). In seals' organs the variation in mass dependent fractionation (MDF, δ(202)Hg) for total Hg was significantly correlated to the respective fraction of iHg and MMHg compounds, with MMHg being enriched by ∼ 3‰ in heavier isotopes relative to iHg. On the other hand, we observe insignificant variation in Hg mass independent isotope fractionation (MIF, Δ(199)Hg) among iHg and MMHg in all organs for the same mammal species and MMHg in prey items. MIF signatures suggest that both MMHg and iHg in aquatic mammals have the same origin (i. e. , MMHg from food), and are representative of Hg photochemistry in the water column of the mammal ecosystem. MDF signatures of Hg compounds indicate that MMHg is demethylated in vivo before being stored in the muscle, and the iHg formed is stored in the liver, and to a lesser extent in the kidney, before excretion. Thus, Hg CSIC analysis in mammals can be a powerful tool for tracing the metabolic response to Hg exposure. | [
"Physical and Analytical Chemical Sciences",
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
]
|
10.1002/cbic.201300205 | Rhabdopeptides as insect-specific virulence factors from entomopathogenic bacteria | Six novel linear peptides, named "rhabdopeptides", have been identified in the entomopathogenic bacterium Xenorhabdus nematophila after the discovery of the corresponding rdp gene cluster by using a promoter trap strategy for the detection of insect-inducible genes. The structures of these rhabdopeptides were deduced from labeling experiments combined with detailed MS analysis. Detailed analysis of an rdp mutant revealed that these compounds participate in virulence towards insects and are produced upon bacterial infection of a suitable insect host. Furthermore, two additional rhabdopeptide derivatives produced by Xenorhabdus cabanillasii were isolated, these showed activity against insect hemocytes thereby confirming the virulence of this novel class of compounds. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Immunity, Infection and Immunotherapy"
]
|
10.1002/adma.201803229 | Directional Acoustic Antennas Based on Valley-Hall Topological Insulators | Realizing directional acoustic signal transmittance and reception robust against surrounding noise and competing signals is crucial in many areas such as communication, navigation, and detection for medical and industrial purposes. The fundamentally wide-angled radiation pattern of most current acoustic sensors and transducers displays a major limitation of the performance when it comes to precise targeting and probing of sound particular of interest in human speaking and hearing. Here, it is shown how topological acoustic valley transport can be designed to enable a unique beamforming mechanism that renders a superdirective needle-like sound radiation and reception pattern. The strategy rests on out-coupling valley-polarized edge states, whose beam is experimentally detected in the far-field with 10° width and a sound-intensity enhancement factor ≈10. Furthermore, anti-interference communication is proposed where sound is received from desired directions, but background noise from other directions is successfully suppressed. This type of topological acoustic antenna offers new ways to control sound with improved performance and functionalities that are highly desirable for versatile applications. | [
"Condensed Matter Physics",
"Systems and Communication Engineering"
]
|
10.1103/PhysRevLett.121.140501 | Experimental Study of Nonclassical Teleportation beyond Average Fidelity | Quantum teleportation establishes a correspondence between an entangled state shared by two separate parties that can communicate classically and the presence of a quantum channel connecting the two parties. The standard benchmark for quantum teleportation, based on the average fidelity between the input and output states, indicates that some entangled states do not lead to channels which can be certified to be quantum. It was recently shown that if one considers a finer-grained witness, then all entangled states can be certified to produce a nonclassical teleportation channel. Here we experimentally demonstrate a complete characterization of a new family of such witnesses, of the type proposed in Phys. Rev. Lett. 119, 110501 (2017)PRLTAO0031-900710. 1103/PhysRevLett. 119. 110501 under different conditions of noise. We report nonclassical teleportation using quantum states that cannot achieve average fidelity of teleportation above the classical limit. We further use the violation of these witnesses to estimate the negativity of the shared state. Our results have fundamental implications in quantum information protocols and may also lead to new applications and quality certification of quantum technologies. | [
"Fundamental Constituents of Matter",
"Computer Science and Informatics"
]
|
171621 | The first ground stations network enabling real-time, cost-effective, and easy access to micro/nanosatellite data | The objective of the LEAF LINE project is to capture the value of the blossoming nano/microsatellites Space market, offering a complete service pack for telecommunication able to maximise the connection time/data transmission rate with satellites.
Nano/microsatellites are opening up a range of new opportunities in the Earth Observation industry: they can perform many operations that, until few years ago, were carried only by large satellites, but at a fraction of the cost. Lots of new satellite operators (e.g. insurance companies, geologists, food companies, environmental agencies, research centers, etc.), are all asking for reliable, cheap, up-to-date and frequent data from Space. However, most of the telecommunications between microsatellites and the Earth are performed by point-to-point link with a single ground station (GS) and the standard connection is limited to around 10-50 minutes per day. This results in a poor usage of the GS, which remains inactive for most of the day. The LEAF LINE project aims to set-up a network of ground stations for managing satellite data, with substantial increase of connection time (up to 7 times for each satellite) and optimized usage of each GS (up to 12 hours a day). The service will be based on the following components:
1. A multi-protocol ground station network, which implements both the low-performance frequencies, VHF-UHF, and S-band and X-band, allowing an easy switching to the band needed for communicating with all the satellites in orbit.
2. An on-board device optimized for the LEAF LINE network, ensuring the best connection performance in line with the customer needs.
3. The overall software infrastructure that coordinates the network of GSs by Leaf Space, ensuring proper tracking of the satellites, and the handshake between several GSs serving the same satellite. The software allows coordinating the GSs with the satellite constellation, thus increasing the overall transmission time for each GS up to 12 hours a day. | [
"Systems and Communication Engineering",
"Products and Processes Engineering",
"Universe Sciences"
]
|
281180 | Evaluation of Osteoarthritis Progression in a Patient-Specific Manner using Magnetic Resonance Imaging and Computational Modeling | Background
Osteoarthritis (OA) is one of the most prevalent disorders of the musculoskeletal system. In OA, articular cartilage degenerates and its structure and mechanical properties change, but monitoring or predicting the progression of OA has not been possible. Magnetic resonance imaging (MRI) is a potential tool for the imaging of joint tissues, estimating cartilage structure and diagnostics of OA, whereas joint loading and estimation of stresses/strains within joint tissues necessitates computational modeling. It would be a major breakthrough if one could develop a technique where, based on MRI and computational modeling, prediction and evaluation of OA progression of a patient under a certain loading condition would be possible.
Objectives
1) to combine MRI with computational modeling for the estimation of stresses and possible failure points within human knee joints, and 2) to develop second generation adaptive models of articular cartilage for the prediction of altered tissue structure and composition during OA progression. For the model validation, cartilage structure, composition and biomechanical properties as well as cell responses in situ are characterized. At the end of the project these main aims will be merged 3) to estimate the effect of loading on cartilage degeneration during the progression of OA in a patient-specific manner.
Significance
Combining MRI information of joint tissues with computational modeling, we develop a tool to evaluate the effect of different interventions on stresses in human joints. By combining this tool with an adaptive model that can estimate the effect of loading on cartilage composition and structure, we hope to be able to predict changes in cartilage properties during OA progression in a patient-specific manner several years ahead. This would help in decision making of clinical treatments and interventions (conservative or surgical) for the prevention or further progression of OA. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering",
"Physiology in Health, Disease and Ageing",
"Computer Science and Informatics"
]
|
10.1038/srep00812 | There is more than a power law in Zipf | The largest cities, the most frequently used words, the income of the richest countries, and the most wealthy billionaires, can be all described in terms of Zipf's Law, a rank-size rule capturing the relation between the frequency of a set of objects or events and their size. It is assumed to be one of many manifestations of an underlying power law like Pareto's or Benford's, but contrary to popular belief, from a distribution of, say, city sizes and a simple random sampling, one does not obtain Zipf's law for the largest cities. This pathology is reflected in the fact that Zipf's Law has a functional form depending on the number of events N. This requires a fundamental property of the sample distribution which we call 'coherence' and it corresponds to a 'screening' between various elements of the set. We show how it should be accounted for when fitting Zipf's Law. | [
"Mathematics"
]
|
US 2011/0063007 W | CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USED RELATED THERETO | The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1038/s41467-018-07338-z | Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap | Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activation of the p62/Sqstm1-Nrf2 axis. Here, we show that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis. Hepatocyte-specific deletion of Atg7 promotes liver size, fibrosis, progenitor cell expansion, and hepatocarcinogenesis, which is rescued by concurrent deletion of Yap. Our results shed new light on mechanisms of Yap degradation and the sequence of events that follow disruption of autophagy, which is impaired in chronic liver disease. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
10.15184/aqy.2015.20 | Characterising copper-based metals in Britain in the first millennium AD: a preliminary quantification of metal flow and recycling | Abstract | [
"The Study of the Human Past",
"Materials Engineering"
]
|
W2622301116 | State Aids granted by regional airports: a two-sided market analysis | A lot of cases had arouse in the past decade about agreements between regional airports and low-cost carriers. These agreements are challenged on the basis of the State Aids European control as they rise concerns not only about competition distortions between airlines but also about fiscal competition risks among Member States or local governments. Such phenomena could be expected as regional airports are characterized by significant overcapacities and overlapping inducing a substitutability for airlines. Surprisingly, the new 2014 guidelines on State Aids granted to airlines open the way to transitory operating aid schemes, an option apparently at odds with the European longstanding principles. Our purpose in this paper is to demonstrate with the help of the development of a model, that such agreements can make sense from the economic point of view provided that the relationship between the carrier and the airport is no longer analyzed as a vertical chain, inducing an assessment in terms of economic dependence, but as a two-sided market. The favorable usage terms granted to low cost carriers generate additional flows on the other side, with commercial revenues from shops or parking. Consequently, subsidizing operating costs might be rational, even for a private investor in a market economy, and might be a perennial device. | [
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems"
]
|
W1845319819 | Influence of family carers on haemodialyzed patients’ adherence to dietary and fluid restrictions: an observational study | To determine the influence of a family carer on haemodialyzed patients''adherence'. There is extensive evidence showing that successful treatment of patients with end-stage renal disease is directly related to patients''adherence'. The parameters indicative of a good adherence are potassium and phosphate serum levels and the interdialytic weight gain. Haemodialyzed patients may have scarce adherence to food and fluid intake restrictions, and medications schedule. Case-control study carried out in a haemodialysis centre in Italy. The data were collected during 2010. A total of 72 subjects with end-stage renal disease participated in the study. The subjects assisted by a family carer were identified as cases (n = 36), whereas those who did not have a family carer, as controls (n = 36). All subjects were followed up (4 months) and checked up regarding interdialytic weight gain, and serum levels of potassium and phosphate. Important differences in potassium and phosphate serum level and interdialytic weight gain between the two groups were evaluated separately using a repeated measures anova test. Participants in the case group showed significantly lower phosphate and potassium serum levels and a lower interdialytic weight gain during follow-up when compared to controls. The presence of a family carer improves patients' adherence, particularly as far as phosphate levels are concerned, since phosphate intake plays a fundamental role in avoiding long-term complications in end-stage renal disease patients. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
]
|
IL 2016050045 W | MODULAR IN LINE BUTTON DRIP EMITTER SYSTEM | A modular in-line drip emitter may include a flow restrictor and a replaceable attachment. The flow restrictor may provide fluid communication between an inlet and a fluid outlet chamber. The flow restrictor may include rate limiting fluid path producing a predefined range of flow rate over a predefined pressure differential range between the fluid inlet and the fluid outlet. The attachment may be sized and shaped to mount to the flow restrictor. In some embodiments the attachment includes an inlet opening oriented for receiving fluid from a conduit and a fluid outlet attachable to the fluid inlet of the flow restrictor. In some embodiments the attachment includes a sleeve fitting into a conduit with an annular outlet chamber attachable to the outlet chamber of the flow restrictor. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
10.1007/978-3-319-58895-7_5 | Supermodeling Synchronization Of Alternative Dynamical Models Of A Single Objective Process | Imperfect models of the same objective process give an improved representation of that process, from which they assimilate data, if they are also coupled to one another. Inter-model coupling, through nudging, or more strongly through averaging of dynamical tendencies, typically gives synchronization or partial synchronization of models and hence formation of consensus. Previous studies of supermodels of interest for weather and climate prediction are here reviewed. The scheme has been applied to a hierarchy of models, ranging from simple systems of ordinary differential equations, to models based on the quasigeostrophic approximation to geophysical fluid dynamics, to primitive-equation fluid dynamical models, and finally to state-of-the-art climate models. Evidence is reviewed to test the claim that, in nonlinear systems, the synchronized-model scheme surpasses the usual procedure of averaging model outputs. | [
"Mathematics",
"Earth System Science"
]
|
10.1038/ncomms8638 | A new class of chiral materials hosting magnetic skyrmions beyond room temperature | Skyrmions, topologically protected vortex-like nanometric spin textures in magnets, have been attracting increasing attention for emergent electromagnetic responses and possible technological applications for spintronics. In particular, metallic magnets with chiral and cubic/tetragonal crystal structure may have high potential to host skyrmions that can be driven by low electrical current excitation. However, experimental observations of skyrmions have been limited to below room temperature for the metallic chiral magnets, specifically for the MnSi-type B20 compounds. Towards technological applications, transcending this limitation is crucial. Here we demonstrate the formation of skyrmions with unique spin helicity both at and above room temperature in a family of cubic chiral magnets: b-Mn-type Co-Zn-Mn alloys with a different chiral space group from that of B20 compounds. Lorentz transmission electron microscopy, magnetization and small-angle neutron scattering measurements unambiguously reveal formation of a skyrmion crystal under application of a magnetic field in both thin-plate and bulk forms. | [
"Condensed Matter Physics",
"Materials Engineering",
"Synthetic Chemistry and Materials"
]
|
W1973434424 | Maria Montessori's Epistemology | This paper lays out the epistemology of Maria Montessori (1870–1952). I start with what I call Montessori's ‘interested empiricism’, her empiricist emphasis on the foundational role of the senses combined with her (broadly Jamesian) insistence that all cognition is infused with ‘interest’. I then discuss the unconscious. Partly because of her emphasis on early childhood, Montessori puts great emphasis on unconscious cognitive processes and develops a conceptual vocabulary to make sense of the continuity between conscious and unconscious processes. The final sections turn to two brief but important applications of this general epistemic framework, the importance of ‘meditation’ as an epistemic practice and Montessori's accounts of epistemic virtues. | [
"Texts and Concepts",
"The Human Mind and Its Complexity"
]
|
322491 | Intersecting hallmarks of cancer: mechanisms of and interplay between invasion and angiogenesis, guiding new strategies for cancer therapy | Acquisition of the hallmark capability for invasion and in turn metastasis is for most human cancers the defining event in progression to life threatening disease. Its determinants are remarkably complex. Genetically engineered mice can model human cancers, with tumors arising in specific organs, reflecting onco-genomic and histopathological features of particular tumor types. This project will use four mouse models to characterize newly implicated determinants of invasive tumor growth. We have observed that genetic polymorphisms can govern predisposition to invasive cancer. Additionally, therapeutic targeting of another hallmark capability – tumor angiogenesis – has revealed adaptive resistance, whereby late-stage tumors, faced with the inability to grow en masse supported by angiogenesis, switch instead to grow diffusively, by invading adjacent tissue; this phenomenon may underlay the limited benefit seen with anti-angiogenic therapies in the clinic. There are three interconnected goals:
(1) Polymorphic regulation of tumor invasion. We will investigate the mechanisms and functional importance of candidate genes resident within a genetic modifier locus on mouse Chr 17 that can alternatively suppress or facilitate invasive tumor growth dependent on constitutional genetic background.
(2) Adaptive induction of invasion. We will elucidate the determinants of the invasive growth capability that is induced in response to potent inhibition of angiogenesis.
(3) Testing mechanism-based therapeutic co-targeting of the capabilities for invasion and angiogenesis.
We will use functional genetic, genomic profiling, and pharmacological approaches to assess these two new modes of regulating invasive growth, and then apply the knowledge in preclinical trials aiming to lay the groundwork for future clinical trials in which these intersecting hallmark capabilities are coordinately disrupted, with promise for more enduring therapeutic responses and benefit to cancer patients. | [
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1007/978-3-319-27810-0_5 | An Automata Based Approach To Trace Partitioned Abstract Interpretation | Trace partitioning is a technique for retaining precision in abstract interpretation, by partitioning all traces into a number of classes and computing an invariant for each class. In this work we present an automata-based approach to trace partitioning, by augmenting the finite automaton given by the control-flow graph with abstract transformers over a lattice. The result is a lattice automaton, for which efficient model-checking tools exist. By adding additional predicates to the automaton, different classes of traces can be distinguished. This shows a very practical connection between abstract interpretation and model checking: a formalism encompassing problems from both domains, and accompanying machinery that can be used to solve problems from both domains efficiently. This practical connection has the advantage that improvements from one domain can very easily be transferred to the other. We exemplify this with the use of multi-core processors for a scalable computation. Furthermore, the use of a modelling formalism as intermediary format allows the program analyst to simulate, combine and alter models to perform ad-hoc experiments. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
10.1002/chem.201603318 | Enantioselective Stereodivergent Nucleophile-Dependent Isothiourea-Catalysed Domino Reactions | α,β-Unsaturated acyl ammoniums generated from the reaction of α,β-unsaturated 2,4,6-trichlorophenol (TCP) esters bearing a pendent enone with an isothiourea organocatalyst are versatile intermediates in a range of enantioselective nucleophile-dependent domino processes to form complex products of diverse topology with excellent stereoselectivity. Use of either 1,3-dicarbonyls, acyl benzothiazoles, or acyl benzimidazoles as nucleophiles allows three distinct, diastereodivergent domino reaction pathways to be accessed to form various fused polycyclic cores containing multiple contiguous stereocentres. | [
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
]
|
224285 | The mitochondrial unfolded protein response | Mitochondria—organelles specialized in energy harvesting through oxidative phosphorylation (Oxphos)—critically influence metabolism, health and lifespan. Evolved from endosymbiotic proteobacteria, mitochondria retained the vestige of the bacterial genome, the mitochondrial DNA, which encodes 13 subunits of the Oxphos complexes, while the remaining ~80 Oxphos components and the rest of the mitochondrial proteome are encoded on nuclear DNA, translated in the cytoplasm and imported in the mitochondria. The control of the mitochondrial proteome by two genomes exposes these organelles to proteotoxic stress in case of an imbalance between the nuclear- and mitochondrial-encoded proteins. Upon such stress, several mitochondrial protein quality control (mtPQC) pathways, including the mitochondrial unfolded protein response (UPRmt), will sense, transmit and re-establish mitochondrial proteostasis through mitonuclear regulatory circuits. Although a robust UPRmt circuit improves health and lifespan in C. elegans, much less is known about mtPQC in vertebrates. We propose here to characterize UPRmt pathways across 3 species by: (1) mapping mammalian UPRmt genes and networks in vivo after the induction of the UPRmt in a large murine genetic reference population at 3 different times throughout life with 2 different inducers; (2) integrating these UPRmt networks with a wide set of clinical, mitochondrial, and molecular phenotypes collected throughout life to establish links between UPRmt mechanisms and health- and lifespan; (3) mechanistically validating the most important UPRmt pathways, using loss-of-function studies in cells, worms and mice; and (4) clinically translating promising UPRmt hits, using genetic association studies in human cohorts. The insight gained will mechanistically define the UPRmt networks from worms to humans and will provide the next step in translating the benefits of activating the UPRmt—initially observed in invertebrates—into targeted human therapies. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1007/JHEP09(2014)021 | Quantum Phase Transitions In Mass Deformed Abjm Matrix Model | When mass-deformed ABJM theory is considered on S(3), the partition function of the theory localises and is given by a matrix model. We solve this model at large-N in the decompactification limit, where the radius of the three-sphere is taken to infinity. In this limit, the theory exhibits a rich phase structure with an infinite number of third-order quantum phase transitions accumulating at strong coupling. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
307320 | Microbial formation of minerals by communities of Fe(II)-oxidizing bacteria in modern and ancient environments | Iron minerals are ubiquitously present in the environment. Their formation is linked to the global C and N cycle and they control the fate of nutrients, metals, and greenhouse gases. My recent work, published in international journals including Nature Geoscience, showed that Fe(II)-oxidizing bacteria form Fe(III) minerals and suggested that such bacteria were involved in the deposition of Precambrian Banded Iron Formations, the world’s largest iron mineral deposits. Three neutrophilic microbial groups contribute to Fe(III) mineral formation: microaerophiles, phototrophs and nitrate-reducing Fe(II)-oxidizers. However, as previous studies have always solely focused on only one particular Fe(II) metabolism, the contribution of the different Fe(II)-oxidizing groups to overall Fe(III) mineral formation in nature and the competition among them for Fe(II) within Fe(II)-oxidizing communities is still unknown. I propose to use an innovative and holistic approach to study for the first time the abundance, activity and spatial distribution of all three Fe(II)-oxidizing bacterial groups in one habitat in different environments. Quantification of microbial activity and both nutrient and metal sorption under varying geochemical conditions will allow us to study competition among the Fe(II)-oxidizing groups and evaluate the ecological importance of microbial Fe(III) mineral formation in both early Earth and modern environments. This requires an interdisciplinary frontier research effort at the scale of an ERC grant integrating microbiology, biogeochemistry and mineralogy. Central to this is the cultivation and characterization of Fe(II)-oxidizing bacteria and their mineral products, a research area spearheaded by my group. This frontier research will define the role of microbial iron mineral formation in modern and ancient Earth systems, open doors to new biotechnology applications and advance the search for life on the Fe-rich planet Mars. | [
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1109/IRPS.2014.6861097 | Breakdown Mechanisms In Mgo Based Magnetic Tunnel Junctions And Correlation With Low Frequency Noise | Magnetic tunnel junctions (MTJs) are very attractive for magnetic random access memories (MRAMs), thanks to their combination of non-volatility, speed, low power and endurance. In particular spin transfer torque (STT) RAMs based on STT writing show a very good downsize scalability. However, an issue is that at each write event, the MTJ is submitted to an important electrical stress due to write voltage of the order of half of the electrical breakdown voltage. Here we present a study of breakdown mechanisms in MgO based MTJ performed under pulsed conditions. We developed a model of charge trapping/detrapping on barrier defects to explain and predict device endurance. We also show that endurance is correlated to low frequency 1/f noise and that such noise measurement could thus be used as a non destructive and predictive tool for the reliability of the devices. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
W4220848519 | Ley de refuerzo del respeto de los principios republicanos en Francia. ¿El regreso del asimilacionismo? | Este artículo estudia la evolución de las prácticas de la República francesa en materia de integración desde principios de siglo XIX hasta la actualidad, con la nueva ley titulada «ley de refuerzo del respeto de los principios republicanos» de 24 de agosto de 2021. Se aportan perspectivas históricas y legales que esclarecen los fundamentos y los objetivos de la praxis francesa. A través de este trabajo se intenta demostrar que el asimilacionismo, fundamentado en el proyecto republicano de unificación de la nación, es un modelo que está resurgiendo parcialmente tras un paréntesis liberal favorable a las reivindicaciones de las minorías. Para llevar a cabo este objetivo, se aborda, en primer lugar, el marco ideológico en el que nace el asimilacionismo; en segundo lugar, se analiza la forma en que ese modelo se fue imponiendo antes de su declive a partir de los años sesenta; y, finalmente, se discute si la nueva ley marca el retorno del asimilacionismo. | [
"The Study of the Human Past",
"Institutions, Governance and Legal Systems"
]
|
10.1177/1527476419837739 | Big Data From The South S Beyond Data Universalism | This article introduces the tenets of a theory of datafication of and in the Souths. It calls for a de-Westernization of critical data studies, in view of promoting a reparation to the cognitive injustice that fails to recognize non-mainstream ways of knowing the world through data. It situates the “Big Data from the South” research agenda as an epistemological, ontological, and ethical program and outlines five conceptual operations to shape this agenda. First, it suggests moving past the “universalism” associated with our interpretations of datafication. Second, it advocates understanding the South as a composite and plural entity, beyond the geographical connotation (i. e. , “global South”). Third, it postulates a critical engagement with the decolonial approach. Fourth, it argues for the need to bring agency to the core of our analyses. Finally, it suggests embracing the imaginaries of datafication emerging from the Souths, foregrounding empowering ways of thinking data from the margins. | [
"Texts and Concepts",
"The Social World and Its Interactions",
"Studies of Cultures and Arts"
]
|
10.3390/ijms21176048 | EVs and Bioengineering: From Cellular Products to Engineered Nanomachines | Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i. e. , engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications. | [
"Biotechnology and Biosystems Engineering",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Synthetic Chemistry and Materials"
]
|
interreg_3634 | international Tourism | "This project is part of the plan TERRES MONVISO" :Terres Monviso – T(o)UR’s project aims to increase the touristic positioning of the cross-border territory on international markets. The project takes concrete actions allowing the appropriateness of the welcoming needs of touristic demand and which can come in thanks to the achievement of the touristic information network distributed on the area, including activation of new services dedicated to users, and the complete coordination of this network thanks to the implication of local administrators and the levelling of pre-existing realities on both sides of the border.
This PITER aims to create a permanent collaboration for a coordinated gestion of development policies in a homogeneous and well-defined area, the cross-border area of Monviso, thorough the development of new instruments of territorial concertation and the creation of a touristic cross-border destination linked to Monviso. The strategy confirm an high implication of local political institutions, Monviso territory as territorial and identarian aggregation and of a declared political will de front together common problematics of local development thorough 4 simple projects on the 4 axes of the program: Green Economy “research and innovation”, Risk “risks prevention”, ToUR “natural and cultural heritage”, and Incl “health and social services”. | [
"Human Mobility, Environment, and Space",
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
642768 | Bridging the evolutionary gap between unicellular endosymbiotic cyanobacteria and organelles | Symbiosis has been key to evolution on Earth. The success of eukaryotes was possible due to the establishment of endosymbiotic relationships between unicellular microorganisms that gave rise to specialized organelles (chloroplasts and mitochondria), yet the mechanisms underpinning such biological innovations are still unresolved. An unusual marine nitrogen-fixing symbiosis involving a cyanobacterium called UCYN-A and a single-celled haptophyte algae (Braarudosphaera bigelowii) was recently found to have undergone genome rearrangements analogous to organelle evolution. Since no eukaryotes fix nitrogen (N2), an essential nutrient for life, knowledge on this peculiar symbiosis may serve as a unique opportunity for understanding the acquisition of new organelle-derived functions in eukaryotes. The UCYNELLE project is designed to provide new insights on organelle evolution through the multidisciplinary study of the UCYN-A symbiosis from an ecological, evolutionary and metabolic perspective: First, experimental manipulations with the UCYN-A culture and field surveys will be conducted to identify the molecular basis regulating the metabolic coupling between symbiotic partners and the associated microbiome. Second, the organelle genomes of the haptophyte host will be compared to those of the different UCYN-A lineages via comparative genomics to explore any parallelisms in their mode of evolution. Finally, the natural variation in cell size shown by UCYN-A and its host across different UCYN-A symbioses will allow investigating the metabolic scaling (metabolic rates vs cell size) of the N2 fixation process compared to that of typical organelle-driven metabolisms (photosynthesis and respiration) through the study of the volumetric relationships between chloroplasts, mitochondria, UCYN-A and its host. Elucidating the mechanism underlying the UCYN-A symbiosis will help to understand the early evolutionary steps leading to the acquisition of plastids in eukaryotes. | [
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.3389/fphys.2020.00751 | Muscle Synergies and Coherence Networks Reflect Different Modes of Coordination During Walking | When walking speed is increased, the frequency ratio between the arm and leg swing switches spontaneously from 2:1 to 1:1. We examined whether these switches are accompanied by changes in functional connectivity between multiple muscles. Subjects walked on a treadmill with their arms swinging along their body while kinematics and surface electromyography (EMG) of 26 bilateral muscles across the body were recorded. Walking speed was varied from very slow to normal. We decomposed EMG envelopes and intermuscular coherence spectra using non-negative matrix factorization (NMF), and the resulting modes were combined into multiplex networks and analyzed for their community structure. We found five relevant muscle synergies that significantly differed in activation patterns between 1:1 and 2:1 arm-leg coordination and the transition period between them. The corresponding multiplex network contained a single module indicating pronounced muscle co-activation patterns across the whole body during a gait cycle. NMF of the coherence spectra distinguished three EMG frequency bands: 4–8, 8–22, and 22–60 Hz. The community structure of the multiplex network revealed four modules, which clustered functional and anatomical linked muscles across modes of coordination. Intermuscular coherence at 4–22 Hz between upper and lower body and within the legs was particularly pronounced for 1:1 arm-leg coordination and was diminished when switching between modes of coordination. These findings suggest that the stability of arm-leg coordination is associated with modulations in long-distant neuromuscular connectivity. | [
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing",
"Computer Science and Informatics"
]
|
10.1039/c5sc01960e | A curve-crossing model to rationalize and optimize diarylethene dyads | Extra crossing points play a key role in the photochemistry of diarylethene dyads. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
W302008360 | Chalk Talks- Autism, Schools, and Service Animals: What Must and Should Be Done | I. INTRODUCTION Kaleb Drew looks like other blonde 6-year-old child in central Illinois. However, when it comes communicating, Kaleb is not like other 6-year-olds. Kaleb has autism. When the Drews sought have a service dog accompany Kaleb at school, his school refused. The school administrators argued that service animals do not properly assist autistic students and that the school must protect the other students from Kaleb 's Labrador Retriever.1 Kaleb's family took the issue court and won. Kaleb entered first grade accompanied by his dog, Chewey.2 This Note advises school administrators of the issues and laws surrounding a student's service animal request as well as the specific issues presented by a student who has an autism spectrum disorder. Section II explains three federal statutes that govern the treatment of individuals with Section III addresses the problems associated with autism and explains the ways that service animals can assist students. Section IV explains the factors that can allow a school forbid a student from bringing a service animal school. These factors include both the broad issues and the autism-specific reasons for a legal denial of service animal use. Lastly, Section V provides a solution which allows school administrators better serve current and future students who make service animal requests. II. LAWS APPLICABLE TO STUDENTS WITH DISABILITIES, SERVICE ANIMALS, AND SCHOOLS Part of the problem of dealing with students with disabilities is that there are multiple laws addressing the issues surrounding individuals with disabilities bringing service animals into schools. Service animals are defined as any guide dog, signal dog, or other animal individually trained do work or perform tasks for the benefit of an individual with a disability.3 Although some states have enacted laws which address a student's right attend school with a service animal,4 three primary federal statutes that apply schools and how they must accommodate requests by students with disabilities bring service animals into schools will discussed here. These statutes are the Rehabilitation Act, Americans with Disabilities Act, both of which impose a duty not discriminate against the disabled,5 and the Individuals with Disabilities Education Act, which imposes a duty provide a free appropriate public education the disabled.6 A. Section 504 of the Rehabilitation Act The Rehabilitation Act, passed in 1973, provides that no qualified individual with a disability be excluded from the participation in, denied the benefits of, or subjected by program receiving federal financial assistance.7 It established that recipients of federal financial assistance (Section 504) should not discriminate against otherwise qualified individuals with disabilities.8 Accordingly, Section 504 bars schools, as entities which receive federal funding, from discriminating against disabled individuals.9 If a reasonable accommodation (see discussion below in Section B) allows a disabled student more mobile, communicate better, learn more, care for himself, or perform other manual tasks, then a school should allow that accommodation. In many cases, a service animal can help an autistic student with these major life activities. If the service animal has been individually trained and ameliorates the unique problems of the disabled student, then the school generally should not ban the animal. Under Section 504, the service animal's presence and assistance need only necessary allow the disabled student participate in or receive the benefits of activity that is afforded other students.10 B. Americans with Disabilities Act Congress passed the Americans with Disabilities Act of 1990 (ADA) with the goal of further prohibiting discrimination against individuals with disabilities. Congress enacted the ADA to address the major areas of discrimination faced day-to-day by people with … | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.1111/gcb.15004 | Modeling and empirical validation of long-term carbon sequestration in forests (France, 1850–2015) | The development of appropriate tools to quantify long-term carbon (C) budgets following forest transitions, that is, shifts from deforestation to afforestation, and to identify their drivers are key issues for forging sustainable land-based climate-change mitigation strategies. Here, we develop a new modeling approach, CRAFT (CaRbon Accumulation in ForesTs) based on widely available input data to study the C dynamics in French forests at the regional scale from 1850 to 2015. The model is composed of two interconnected modules which integrate biomass stocks and flows (Module 1) with litter and soil organic C (Module 2) and build upon previously established coupled climate-vegetation models. Our model allows to develop a comprehensive understanding of forest C dynamics by systematically depicting the integrated impact of environmental changes and land use. Model outputs were compared to empirical data of C stocks in forest biomass and soils, available for recent decades from inventories, and to a long-term simulation using a bookkeeping model. The CRAFT model reliably simulates the C dynamics during France's forest transition and reproduces C-fluxes and stocks reported in the forest and soil inventories, in contrast to a widely used bookkeeping model which strictly only depicts C-fluxes due to wood extraction. Model results show that like in several other industrialized countries, a sharp increase in forest biomass and SOC stocks resulted from forest area expansion and, especially after 1960, from tree growth resulting in vegetation thickening (on average 7. 8 Mt C/year over the whole period). The difference between the bookkeeping model, 0. 3 Mt C/year in 1850 and 21 Mt C/year in 2015, can be attributed to environmental and land management changes. The CRAFT model opens new grounds for better quantifying long-term forest C dynamics and investigating the relative effects of land use, land management, and environmental change. | [
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
]
|
10.1063/1.4921106 | Communication Water On Hexagonal Boron Nitride From Diffusion Monte Carlo | Despite a recent flurry of experimental and simulation studies, an accurate estimate of the interaction strength of water molecules with hexagonal boron nitride is lacking. Here, we report quantum Monte Carlo results for the adsorption of a water monomer on a periodic hexagonal boron nitride sheet, which yield a water monomer interaction energy of −84 ± 5 meV. We use the results to evaluate the performance of several widely used density functional theory (DFT) exchange correlation functionals and find that they all deviate substantially. Differences in interaction energies between different adsorption sites are however better reproduced by DFT. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
]
|
10.1007/s00410-015-1156-1 | Thermodynamic equilibrium at heterogeneous pressure | Recent advances in metamorphic petrology point out the importance of grain-scale pressure variations in high-temperature metamorphic rocks. Pressure derived from chemical zonation using unconventional geobarometry based on equal chemical potentials fits mechanically feasible pressure variations. Here, a thermodynamic equilibrium method is presented that predicts chemical zoning as a result of pressure variations by Gibbs energy minimization. Equilibrium thermodynamic prediction of the chemical zoning in the case of pressure heterogeneity is done by constrained Gibbs minimization using linear programming techniques. In addition to constraining the system composition, a certain proportion of the system is constrained at a specified pressure. Input pressure variations need to be discretized, and each discrete pressure defines an additional constraint for the minimization. The Gibbs minimization method provides identical results to a geobarometry approach based on chemical potentials, thus validating the inferred pressure gradient. The thermodynamic consistency of the calculation is supported by the similar result obtained from two different approaches. In addition, the method can be used for multi-component, multi-phase systems of which several applications are given. A good fit to natural observations in multi-phase, multi-component systems demonstrates the possibility to explain phase assemblages and zoning by spatial pressure variations at equilibrium as an alternative to pressure variation in time due to disequilibrium. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
10.1242/jeb.091009 | Complex vibratory patterns in an elephant larynx | Elephants' low-frequency vocalizations are produced by flow-induced self-sustaining oscillations of laryngeal tissue. To date, little is known in detail about the vibratory phenomena in the elephant larynx. Here, we provide a first descriptive report of the complex oscillatory features found in the excised larynx of a 25 year old female African elephant (Loxodonta africana), the largest animal sound generator ever studied experimentally. Sound production was documented with high-speed video, acoustic measurements, air flow and sound pressure level recordings. The anatomy of the larynx was studied with computed tomography (CT) and dissections. Elephant CT vocal anatomy data were further compared with the anatomy of an adult human male. We observed numerous unusual phenomena, not typically reported in human vocal fold vibrations. Phase delays along both the inferior-superior and anterior-posterior (A-P) dimension were commonly observed, as well as transverse travelling wave patterns along the A-P dimension, previously not documented in the literature. Acoustic energy was mainly created during the instant of glottal opening. The vestibular folds, when adducted, participated in tissue vibration, effectively increasing the generated sound pressure level by 12 dB. The complexity of the observed phenomena is partly attributed to the distinct laryngeal anatomy of the elephant larynx, which is not simply a large-scale version of its human counterpart. Travelling waves may be facilitated by low fundamental frequencies and increased vocal fold tension. A travelling wave model is proposed, to account for three types of phenomena: A-P travelling waves, 'conventional' standing wave patterns, and irregular vocal fold vibration. | [
"Condensed Matter Physics",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1126/sciadv.aaw4137 | Direct observation of topological edge states in silicon photonic crystals: Spin, dispersion, and chiral routing | Topological protection in photonics offers new prospects for guiding and manipulating classical and quantum information. The mechanism of spin-orbit coupling promises the emergence of edge states that are helical, exhibiting unidirectional propagation that is topologically protected against back scattering. We directly observe the topological states of a photonic analog of electronic materials exhibiting the quantum spin Hall effect, living at the interface between two silicon photonic crystals with different topological order. Through the far-field radiation that is inherent to the states' existence, we characterize their properties, including linear dispersion and low loss. We find that the edge state pseudospin is encoded in unique circular far-field polarization and linked to unidirectional propagation, thus revealing a signature of the underlying photonic spin-orbit coupling. We use this connection to selectively excite different edge states with polarized light and directly visualize their routing along sharp chiral waveguide junctions. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
819025 | The Consequences of the Internet for Russia's Informational Influence Abroad | Over the past decade, Russia’s ruling elites have massively stepped up their efforts to influ-ence media audiences abroad. Amongst others, Russia has been alleged to have sought to sway votes in Austria, France, Germany, Ukraine, and the US. This project’s overarching research ques-tion is: How, and with what consequences, have new Internet-based technologies contributed to the emergence of novel resources, techniques, and processes by which political elites in Moscow can influence media audiences abroad?
In order to address this question, a theoretical work package (WP4) will undertake the first major systematic effort to interrogate how much, or how little, we can leverage extant in-depth knowledge of former-Soviet foreign propaganda, conducted in the broadcast era, in order to make sense of Russia’s recent digitally-enabled efforts.
WP4 will be informed by three empirical WPs. They will scrutinize three heavily digitally-enabled elements of Russia’s recent efforts:
• WP1 will conduct the first in-depth study of the foreign online audiences who co-create and disseminate Russia-related content.
• WP2 will produce pioneering research about how social media platforms function as key transmission channels that connect Russia’s domestic media with Russian-speaking audiences abroad.
• WP3 will be the first study to scrutinize the role of the Kremlin-controlled search engine Yan-dex as a resource of foreign influence.
Methodologically, WP1-3 are highly innovative because they combine new computational methods (data mining, automated text analysis) with traditional methods (surveys, in-depth inter-views, grounded theory).
In response to Russia’s recent efforts, countermeasures have been ushered in by a plurality of actors, including the EU, NATO, and NGOs. These actors will benefit immensely from the knowledge generated, which will enable them to enhance their initiatives to secure democratic elec-toral processes against undue informational interference. | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions",
"Computer Science and Informatics"
]
|
10.1158/2159-8290.CD-11-0348 | Pi3K Inhibition Impairs Brca1 2 Expression And Sensitizes Brca Proficient Triple Negative Breast Cancer To Parp Inhibition | PARP inhibitors are active in tumors with defects in DNA homologous recombination (HR) due to BRCA1/2 mutations. The phosphoinositide 3-kinase (PI3K) signaling pathway preserves HR steady state. We hypothesized that in BRCA-proficient triple-negative breast cancer (TNBC), PI3K inhibition would result in HR impairment and subsequent sensitization to PARP inhibitors. We show in TNBC cells that PI3K inhibition leads to DNA damage, downregulation of BRCA1/2, gain in poly-ADP-ribosylation, and subsequent sensitization to PARP inhibition. In TNBC patient–derived primary tumor xenografts, dual PI3K and PARP inhibition with BKM120 and olaparib reduced the growth of tumors displaying BRCA1/2 downregulation following PI3K inhibition. PI3K-mediated BRCA downregulation was accompanied by extracellular signal–regulated kinase (ERK) phosphorylation. Overexpression of an active form of MEK1 resulted in ERK activation and downregulation of BRCA1, whereas the MEK inhibitor AZD6244 increased BRCA1/2 expression and reversed the effects of MEK1. We subsequently identified that the ETS1 transcription factor was involved in the ERK-dependent BRCA1/2 downregulation and that knockdown of ETS1 led to increased BRCA1/2 expression, limiting the sensitivity to combined BKM120 and olaparib in 3-dimensional culture. Significance: Treatment options are limited for patients with TNBCs. PARP inhibitors have clinical activity restricted to a small subgroup of patients with BRCA mutations. Here, we show that PI3K blockade results in HR impairment and sensitization to PARP inhibition in TNBCs without BRCA mutations, providing a rationale to combine PI3K and PARP inhibitors in this indication. Our findings could greatly expand the number of patients with breast cancer that would benefit from therapy with PARP inhibitors. On the basis of our findings, a clinical trial with BKM120 and olaparib is being initiated in patients with TNBCs. Cancer Discov; 2(11); 1036–47. Read the Commentary on this article by Rehman et al. , p. 982. This article is highlighted in the In This Issue feature, p. 961 | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
]
|
10.1007/jhep02(2020)072 | Hints of unitarity at large N in the O(N )3 tensor field theory | We compute the OPE coefficients of the bosonic tensor model of [1] for three point functions with two fields and a bilinear with zero and non-zero spin. We find that all the OPE coefficients are real in the case of an imaginary tetrahedral coupling constant, while one of them is not real in the case of a real coupling. We also discuss the operator spectrum of the free theory based on the character decomposition of the partition function. | [
"Fundamental Constituents of Matter",
"Mathematics"
]
|
10.1126/science.1254404 | Language in the aging brain: The network dynamics of cognitive decline and preservation | Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
]
|
10.1371/journal.pgen.1007590 | The methyltransferase HEN1 is required in Nematostella vectensis for microRNA and piRNA stability as well as larval metamorphosis | Small non-coding RNAs (sRNAs) such as microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs) regulate the levels of endogenous, viral and transposable element RNA in plants (excluding piRNAs) and animals. These pathways are explored mainly in bilaterian animals, such as vertebrates, arthropods and nematodes, where siRNAs and piRNAs, but not miRNAs bind their targets with a perfect match and mediate the cleavage of the target RNA. Methylation of the 3′ ends of piRNAs and siRNAs by the methyltransferase HEN1 protects these sRNAs from degradation. There is a noticeable selection in bilaterian animals against miRNA-mRNA perfect matching, as it leads to the degradation of miRNAs. Cnidarians (sea anemones, corals, hydroids and jellyfish), are separated from bilaterians by more than 600 million years. As opposed to bilaterians, cnidarian miRNAs frequently bind their targets with a nearly perfect match. Knowing that an ortholog of HEN1 is widely expressed in the sea anemone Nematostella vectensis, we tested in this work whether it mediates the stabilization of its sRNAs. We show that the knockdown of HEN1 in Nematostella results in a developmental arrest. Small RNA sequencing revealed that the levels of both miRNAs and piRNAs drop dramatically in the morphant animals. Moreover, knockdown experiments of Nematostella Dicer1 and PIWI2, homologs of major bilaterian biogenesis components of miRNAs and piRNAs, respectively, resulted in developmental arrest similar to HEN1 morphants. Our findings suggest that HEN1 mediated methylation of sRNAs reflects the ancestral state, where miRNAs were also methylated. Thus, we provide the first evidence of a methylation mechanism that stabilizes miRNAs in animals, and highlight the importance of post-transcriptional regulation in non-bilaterian animals. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1038/s41477-020-0618-2 | Anthoceros genomes illuminate the origin of land plants and the unique biology of hornworts | Hornworts comprise a bryophyte lineage that diverged from other extant land plants >400 million years ago and bears unique biological features, including a distinct sporophyte architecture, cyanobacterial symbiosis and a pyrenoid-based carbon-concentrating mechanism (CCM). Here, we provide three high-quality genomes of Anthoceros hornworts. Phylogenomic analyses place hornworts as a sister clade to liverworts plus mosses with high support. The Anthoceros genomes lack repeat-dense centromeres as well as whole-genome duplication, and contain a limited transcription factor repertoire. Several genes involved in angiosperm meristem and stomatal function are conserved in Anthoceros and upregulated during sporophyte development, suggesting possible homologies at the genetic level. We identified candidate genes involved in cyanobacterial symbiosis and found that LCIB, a Chlamydomonas CCM gene, is present in hornworts but absent in other plant lineages, implying a possible conserved role in CCM function. We anticipate that these hornwort genomes will serve as essential references for future hornwort research and comparative studies across land plants. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
216680 | Ultra-Low power and highly-scalable interfaces for the internet of things | The era of the Internet of Things (IoT), in which every physical entity includes power-autonomous embedded electronics, capturing relevant information by sensors and interacting with objects and humans in a globally interconnected network, is bringing about new challenges in Integrated Circuit (IC) design. The performance of ICs in terms of integration density, power consumption and cost, in fact, is the only limiting factor to the feasibility and/or to the widespread diffusion of IoT-based solutions.
Digital ICs in the most recent nanoscale CMOS technologies are keeping the pace of IoT requirements. On the contrary, the implementation of analog functions, which are however essential to acquire data from sensors, thus enabling the interactions of IoT nodes with the surrounding environment, is nowadays the real bottleneck and the most serious concern and limiting factor for the further development of IoT applications.
In the foreseeable future, the planned device scaling and voltage reduction down to near threshold (e.g. 0.4-0.5V) makes the design of analog circuits extremely hard, in view of the degradation of signal-to-noise ratio, matching and linearity. Despite of device shrinking, traditional low-voltages analog circuits do not really scale down in size, and occupy a more and more relevant percentage (i.e., cost) of the die area.
In this scenario, the proposed research activity is intended to substantially enhance the scalability of analog blocks with technology and voltage by re-thinking analog functions in ICs in digital terms. In a new cross-domain approach, design and testing methodologies from the digital world will be extended and frontier design concepts like near-threshold operation further exploited.
The effectiveness of the proposed approach will be verified and validated on IC demonstrators and with reference to a full SoC for wearable electronics applications in the development of novel IoT solutions. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1093/nar/gky997 | EndoDB: A database of endothelial cell transcriptomics data | Endothelial cells (ECs) line blood vessels, regulate homeostatic processes (blood flow, immune cell trafficking), but are also involved in many prevalent diseases. The increasing use of high-throughput technologies such as gene expression microarrays and (single cell) RNA sequencing generated a wealth of data on the molecular basis of EC (dys-)function. Extracting biological insight from these datasets is challenging for scientists who are not proficient in bioinformatics. To facilitate the re-use of publicly available EC transcriptomics data, we developed the endothelial database EndoDB, a web-accessible collection of expert curated, quality assured and pre-analyzed data collected from 360 datasets comprising a total of 4741 bulk and 5847 single cell endothelial transcriptomes from six different organisms. Unlike other added-value databases, EndoDB allows to easily retrieve and explore data of specific studies, determine under which conditions genes and pathways of interest are deregulated and assess reprogramming of metabolism via principal component analysis, differential gene expression analysis, gene set enrichment analysis, heatmaps and metabolic and transcription factor analysis, while single cell data are visualized as gene expression color-coded t-SNE plots. Plots and tables in EndoDB are customizable, downloadable and interactive. EndoDB is freely available at https://vibcancer. be/software-tools/endodb, and will be updated to include new studies. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1088/0953-8984/24/38/385803 | Density Functional Simulations Of Sb Rich Gesbte Phase Change Alloys | We generated models of the amorphous phase of Sb-rich GeSbTe phase change alloys by quenching from the melt within density functional molecular dynamics. We considered the two compositions Ge1Sb1Te1 and Ge2Sb4Te5. Comparison with previous results on the most studied Ge2Sb2Te5 allowed us to draw some conclusions on the dependence of the structural properties of the amorphous phase on the alloy composition. Vibrational and electronic properties were also scrutinized. Phonons at high frequencies above 200?cm?1 are localized in tetrahedra around Ge atoms in Sb-rich compounds as well as in Ge2Sb2Te5. All compounds are semiconducting in the amorphous phase, with a band gap in the range 0. 7?1. 0?eV. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Materials Engineering"
]
|
2718728 | Fundamental understanding of reactive nitrogen in the global upper troposphere | The upper troposphere (UT), a severely under-researched part of the atmosphere, has profound impacts on global climate, air quality, major atmospheric oxidants, and the protective ozone layer. Key to its influence on the Earth system are reactive nitrogen compounds (collectively NOy). Models, since their inception, have grossly misrepresented observations of UT NOy, hindering application of these models to accurately estimate the impact of humans on climate, the ozone layer, and air quality. The reasons proposed for discrepancies between models and observations are unsatisfactory, as past studies have been hampered by observations that are limited in space and time. Only now are there unprecedented global, high-resolution measurements of the UT from instruments on aircraft and satellites that can be combined with detailed and advanced modelling tools to at last tackle this issue on a global scale. The ground-breaking UpTrop work programme will innovatively combine observations from the recently launched ESA Sentinel-5P mission and a long record of aircraft campaigns (most crucially the 2016-2018 NASA ATom campaign) to create the first truly global dataset of UT NOy abundance, interpreted with the state-of-the-art GEOS-Chem model. This pioneering multiplatform approach, the bedrock of my previous highly cited work, will deliver game-changing objectives: (i) novel insights into the processes controlling UT NOy, (ii) an unequivocal account of the role of the upper troposphere in altering climate and the chemical composition of the atmosphere, and (iii) interpretation of the disruptive impact of improved understanding of UT NOy on widespread application of satellite observations to constrain global air quality. UpTrop is ambitious, with bold objectives that will conceptually change fundamental understanding of UT NOy and address a challenge that has plagued atmospheric chemists for decades. A cascade of new avenues of cross-disciplinary research is inevitable. | [
"Earth System Science",
"Physical and Analytical Chemical Sciences"
]
|
983166 | Exhaustion-Resistant car-t cells for the treatment of solid tumours | Adoptive transfer of T-cells collected from patient’s blood and engineered to express chimeric antigen receptors (CARs) has produced unprecedented clinical responses in patients with cancer. CAR-T cells targeting CD19 were recently approved by the US food and drug administration (FDA) and the European Commission (EC) for the treatment of leukemia and lymphoma, heralding a new era for cancer treatment. However, despite the stunning results of CAR-T cells in patients with hematologic malignancies, results with CAR-T cells in patients with solid tumors are far from expected. Although CAR-T cells are able to infiltrate solid tumors and exert antigen directed activity, observed responses in patients with solid tumors have been minor and transient. But what are the mechanisms behind the poor T-cell activity in solid tumors? Are CAR-T cells susceptible to dysfunction in a similar way as the endogenous tumor-specific T cells that fail to eliminate the tumors in treatment-naïve cancer patients?
My central hypothesis is that CAR-T cells become exhausted in the tumor microenvironment mainly due to continuous antigen encounter, and that this process can be prevented or delayed. My general aim for this project is to enhance the persistence and function of CAR-T cells by overcoming T-cell dysfunction while promoting T-cell stemness. By using animal models and a combination of innovative technologies, including next-generation sequencing and genome editing I will: 1) elucidate the T-cell intrinsic mechanisms by which CAR-T cells become unresponsive to solid tumors, 2) design new approaches to enable infused T cells to overcome dysfunction and persist within the tumor microenvironment. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
10.1371/journal.pone.0176795 | Selective mitochondrial DNA degradation following double-strand breaks | Mitochondrial DNA (mtDNA) can undergo double-strand breaks (DSBs), caused by defective replication, or by various endogenous or exogenous sources, such as reactive oxygen species, chemotherapeutic agents or ionizing radiations. MtDNA encodes for proteins involved in ATP production, and maintenance of genome integrity following DSBs is thus of crucial importance. However, the mechanisms involved in mtDNA maintenance after DSBs remain unknown. In this study, we investigated the consequences of the production of mtDNA DSBs using a human inducible cell system expressing the restriction enzyme PstI targeted to mitochondria. Using this system, we could not find any support for DSB repair of mtDNA. Instead we observed a loss of the damaged mtDNA molecules and a severe decrease in mtDNA content. We demonstrate that none of the known mitochondrial nucleases are involved in the mtDNA degradation and that the DNA loss is not due to autophagy, mitophagy or apoptosis. Our study suggests that a still uncharacterized pathway for the targeted degradation of damaged mtDNA in a mitophagy/autophagy-independent manner is present in mitochondria, and might provide the main mechanism used by the cells to deal with DSBs. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
632002 | Dissecting the functional and therapeutic impact of somatic copy number alterations (scnas) | In 1914 Theodor Boveri described abnormal chromosome counts in cancer cells and speculated that these alterations are the driving force of cancer. Almost 100 years later it became clear that somatic copy number alterations (SCNAs) are one of the most striking characteristics of cancer genomes. SCNAs comprise deletions and amplifications of whole chromosome arms and therefore alter the expression patterns of several hundred genes simultaneously. These alterations show defined patterns suggesting selective pressure, and thus likely contain multiple driver genes, which can shape several tumorigenic properties. Therefore, studying how these events contribute to tumor development will be fundamental to understand cancer biology and develop targeted cancer therapies. However, whereas the function of recurrently mutated driver genes can be readily assessed, studying SCNAs remains challenging so far. This project will overcome these limitations by combining our unique ability to model liver cancer in vivo and in vitro with innovative CRISPR-based genomic engineering technologies. First, we will generate large chromosomal deletions in murine livers and human-derived liver organoids by CRISPR technologies and assess their functional role in cancer development. Furthermore, synthetic lethal interactions generated by these deletions will be evaluated on their therapeutic potential. Additionally, driver genes and driver gene-combinations of amplified chromosomal regions will be investigated using a novel CRISPR/Cas9-based mouse model for endogenous gene activation and chromosome engineering. Finally, we will exploit a novel concept for targeting cancer cells with specific amplifications. Our unique approach will for the first time systematically investigate the functional role of SCNAs in tumor pathobiology, identify new therapeutic strategies specifically tailored for individual SCNAs, and will therefore have high impact for future efforts to understand and combat cancer. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1063/1.4966991 | Low Magnetic Johnson Noise Electric Field Plates For Precision Measurement | We describe a parallel pair of high voltage electric field plates designed and constructed to minimise magnetic Johnson noise. They are formed by laminating glass substrates with commercially available polyimide (Kapton) tape, covered with a thin gold film. Tested in vacuum, the outgassing rate is less than $5\times10^{-5}$ mbar. l/s. The plates have been operated at electric fields up to 8. 3 kV/cm, when the leakage current is at most a few hundred pA. The design is discussed in the context of a molecular spin precession experiment to measure the permanent electric dipole moment of the electron. | [
"Fundamental Constituents of Matter",
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Systems and Communication Engineering"
]
|
US 2017/0066671 W | OPEN COIL SPRING ASSEMBLIES | Present embodiments provide various open coil spring assemblies which perform like an encased spring assembly. The embodiments have elastic lacings or connections which connect springs to springs or springs to lacings. Various spring embodiments are provided as well as various arrangements for the elastic lacings. All of these features improve compliance and stability while reducing motion transfer. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
10.1038/s41419-018-0848-7 | Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson’s disease | The involvement of DNA damage and repair in aging processes is well established. Aging is an unequivocal risk factor for chronic neurodegenerative diseases, underscoring the relevance of investigations into the role that DNA alterations may have in the pathogenesis of these diseases. Consistently, even moderate impairment of DNA repair systems facilitates the onset of pathological features typical of PD that include derangement of the dopaminergic system, mitochondrial dysfunction, and alpha-synuclein stress. The latter establishes a connection between reduced DNA repair capacity and a cardinal feature of PD, alpha-synuclein pathology. It remains to be determined, however, whether alpha-synuclein stress activates in vivo the canonical signaling cascade associated with DNA damage, which is centered on the kinase ATM and substrates such as γH2Ax and 53BP1. Addressing these issues would shed light on age-related mechanisms impinging upon PD pathogenesis and neurodegeneration in particular. We analyzed two different synucleinopathy PD mouse models based either on intranigral delivery of AAV-expressing human alpha-synuclein, or intrastriatal injection of human alpha-synuclein pre-formed fibrils. In both cases, we detected a significant increase in γH2AX and 53BP1 foci, and in phospho-ATM immunoreactivity in dopaminergic neurons, which collectively indicate DNA damage and activation of the DNA damage response. Mechanistic experiments in cell cultures indicate that activation of the DNA damage response is caused, at least in part, by pro-oxidant species because it is prevented by exogenous or endogenous antioxidants, which also rescue mitochondrial anomalies caused by proteotoxic alpha-synuclein. These in vivo and in vitro findings reveal that the cellular stress mediated by alpha-synuclein—a pathological hallmark in PD—elicits DNA damage and activates the DNA damage response. The toxic cascade leading to DNA damage involves oxidant stress and mitochondrial dysfunction The data underscore the importance of DNA quality control for preservation of neuronal integrity and protection against neurodegenerative processes. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
10.1007/s00220-015-2342-8 | Perturbing Misiurewicz Parameters in the Exponential Family | In one-dimensional real and complex dynamics, a map whose post-singular (or post-critical) set is bounded and uniformly repelling is often called a Misiurewicz map. In results hitherto, perturbing a Misiurewicz map is likely to give a non-hyperbolic map, as per Jakobson’s Theorem for unimodal interval maps. This is despite genericity of hyperbolic parameters (at least in the interval setting). We show the contrary holds in the complex exponential family (Formula Presented) Misiurewicz maps are Lebesgue density points for hyperbolic parameters. As a by-product, we also show that Lyapunov exponents almost never exist for exponential Misiurewicz maps. The lower Lyapunov exponent is −∞ almost everywhere. The upper Lyapunov exponent is non-negative and depends on the choice of metric. | [
"Mathematics"
]
|
10.1002/chem.201505086 | Multiple Decay Mechanisms and 2D-UV Spectroscopic Fingerprints of Singlet Excited Solvated Adenine-Uracil Monophosphate | The decay channels of singlet excited adenine uracil monophosphate (ApU) in water are studied with CASPT2//CASSCF:MM potential energy calculations and simulation of the 2D-UV spectroscopic fingerprints with the aim of elucidating the role of the different electronic states of the stacked conformer in the excited state dynamics. The adenine 1La state can decay without a barrier to a conical intersection with the ground state. In contrast, the adenine 1Lb and uracil S(U) states have minima that are separated from the intersections by sizeable barriers. Depending on the backbone conformation, the CT state can undergo inter-base hydrogen transfer and decay to the ground state through a conical intersection, or it can yield a long-lived minimum stabilized by a hydrogen bond between the two ribose rings. This suggests that the 1Lb, S(U) and CT states of the stacked conformer may all contribute to the experimental lifetimes of 18 and 240 ps. We have also simulated the time evolution of the 2D-UV spectra and provide the specific fingerprint of each species in a recommended probe window between 25 000 and 38 000 cm-1 in which decongested, clearly distinguishable spectra can be obtained. This is expected to allow the mechanistic scenarios to be discerned in the near future with the help of the corresponding experiments. Our results reveal the complexity of the photophysics of the relatively small ApU system, and the potential of 2D-UV spectroscopy to disentangle the photophysics of multichromophoric systems. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2383208550 | Optimal Planning Mathematical Model of Regional Agricultural Water-saving and Its Application | To adjust crop patterns and develop water saving irrigation is the main agricultural water saving measures.To consider the relationship between adjustment of crops patters and development of water saving irrigation,the optimal planning mathematical model of the regional agricultural water saving,in which total minimum investment of regional add water saving irrigation engineering is the objective function,have been established based on type of water resource,agricultural utilizable water,crop patters,water saving irrigation status and suitability of each water saving irrigation technology.To use the mathematical model,the Xinjiang Hotan region optimal agricultural water saving plan that includes optimal crop patters and development scale of water saving irrigation for each crop have been put forward in 2020.To compare with Hotan region agricultural water saving plan by using conventional method,investment of the optimal plan reduces 19.92%. | [
"Products and Processes Engineering",
"Earth System Science"
]
|
2719251 | Optimized dynamic point cloud compression | 3D point clouds are receiving increased attention due to their potential for many important applications, such as real-time 3D immersive telepresence. Compared to traditional video technology, 3D point cloud systems allow free viewpoint rendering, as well as mixing of natural and synthetic objects. However, this improved user experience comes at the cost of increased storage and bandwidth requirements as point clouds are typically represented by the geometry and colour of millions up to billions of 3D points. For this reason, major efforts are being made to develop efficient point cloud compression schemes. The task, however, is very challenging due to the irregular structure of point clouds. To standardize these efforts, the Moving Picture Experts Group (MPEG) launched in January 2017 a call for proposals for 3D point cloud compression technology. In October 2017, the responses were evaluated and the first test model for lossy compression of dynamic point clouds (TMC2) was established. This test model defines a first “common core” algorithm for collaborative work towards the final standard. The aim of OPT-PCC is to contribute to these efforts by developing algorithms that optimize the rate-distortion performance of the test model. OPT-PCC’s objectives are to:
1. O1: build analytical models that accurately describe the effect of the geometry and colour quantization of a 3D point cloud on the bit rate and distortion;
2. O2: develop fast search algorithms that optimize the allocation of the available bit budget between the geometry information and colour information;
3. O3: implement a compression scheme for dynamic 3D point clouds that outperforms the state-of-the-art in terms of rate-distortion performance. The target is to reduce the bit rate by at least 20% for the same reconstruction quality;
4. O4: provide multi-disciplinary training to the researcher in algorithm design, metaheuristic optimisation, computer graphics, and leadership and management skills. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
10.1364/JOSAB.34.000601 | High Repetition Rate Mid Infrared Supercontinuum Generation From 13 To 53 Μm In Robust Step Index Tellurite Fibers | We demonstrate broadband supercontinuum generation over two infrared octaves, spanning from 1. 3 to 5. 3 μm, with an output power of 150 mW in robust step-index tellurite fibers with core diameters between 3. 5 and 4. 3 μm. As a pump source, we use femtosecond mid-IR pulses from a home-built post-amplified optical parametric oscillator tunable between 1. 5 and 4. 0 μm at a 43 MHz repetition rate. We study the influence of core size, pump wavelength, and fiber length to optimize the spectral bandwidth. A key requirement for efficient spectral broadening is a low and rather flat average anomalous dispersion over a wide spectral range that can be tailored accordingly by changing the fiber core diameter. Numerical simulations based on the generalized nonlinear Schrodinger equation are in good agreement with experimental results. | [
"Physical and Analytical Chemical Sciences",
"Systems and Communication Engineering"
]
|
W767433051 | Automatic compilation of bilingual terminologies from comparable corpora | Bilingual terminological resources play a pivotal role in human and machine translation of technical text. Owing to the immense volume of newly produced terminology in the biomedical domain, existing resources suffer from low coverage and they are only available for a limited number of languages. The need for term alignment methods that accurately identify translations of terms, emerges. In this work, we focus on bilingual terminology induction from freely available comparable corpora, i.e. thematically related documents in two or more languages. We investigate different sources of information that determine translation equivalence, including: (a) the internal structure of terms (compositional clue), (b) the surrounding lexical context (contextual clue) and (c) the topic distribution of terms (topical clue). We present four novel compositional alignment methods and we introduce several extensions over existing compositional, context-based and topic-based approaches. Furthermore, we combine the three translation clues in a single term alignment model and we show substantial improvements over the individual translation signals when considered in isolation. We examine the performance of the proposed term alignment methods on closely related (English-French, English-Spanish) language pairs, on a more distant, low-resource language pair (English-Greek) and on an unrelated (English-Japanese) language pair. As an application, we integrate automatically compiled bilingual terminologies with Statistical Machine Translation systems to more accurately translate unknown terms. Results show that an up-to-date bilingual dictionary of terms improves the translation performance of SMT. | [
"Computer Science and Informatics",
"Texts and Concepts"
]
|
225062 | Sex in malaria parasites – from basic biology to targets for transmission blocking interventions. | Sexual development in malaria parasites is critical for disease transmission between infected individuals, and is therefore a major target for the malaria elimination agenda. However, there are currently no effective drugs or vaccines that block parasite transmission to mosquitoes, and we currently do not understand the molecular mechanisms involved. This is primarily because Plasmodium genetics has been slow, with the majority of the genome unexplored. I here propose to conduct the first genome-scale screen for male and/or female fertility genes by leveraging a game-changing genetic system we have developed and recently validated through the first genome-scale in vivo gene KO screen in any parasite. Using simultaneous phenotyping of barcoded mutants, we will conduct the first genome-scale screen for male and/or female fertility genes. My team will systematically map specific biological roles for hundreds of parasite genes, ranging from sex determination to zygote differentiation. We will also overcome the next hurdle in Plasmodium genetics by developing a method for massive parallel phenotyping, using the power of single cell transcriptomics to validate the screen and reveal molecular mechanisms at previously intractable points in the Plasmodium life cycle. This approach has clear translational implications, as it will identify both drug and vaccine candidates. This proposal builds firmly on my outstanding track records in delivering large reverse genetics projects and making ground-breaking discoveries in Plasmodium transmission biology. Its unprecedented breadth and depth will mark a turning point in how gene functions are studied in this important model parasite. I am relocating from the UK to Umeå University, a centre of excellence for pathogen research and innovative genetics, so retaining this important research in the EU of 27 will depend critically on ERC funding. | [
"Immunity, Infection and Immunotherapy",
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1109/TVT.2017.2678167 | Energy Efficient Cross Layer Design Of Wireless Mesh Networks For Content Sharing In Online Social Networks | Bearing in mind the associated security and privacy concerns, users in an online social network (OSN) normally communicate with their direct friends. We propose an energy-efficient cross-layer design for wireless mesh network (WMN) aided content sharing in OSN as a case study of the interplay between OSNs and technological networks. A power control aided WMN is proposed for energy-efficient content sharing. Based on our power control scheme in the physical layer, an interference-constrained-channel-reuse scheme and a Dijkstra algorithm aided energy-efficient routing protocol are invoked for the medium access control layer and for the network layer, respectively. Inspired by the tool of social network analysis, both the singular and composite betweenness metrics are invoked for quantifying the duty-cycle of mesh routers. The former only considers the topology of the mesh backbone, while the latter considers the topologies of both the OSN and the WMN. Furthermore, the singular/composite betweenness is exploited for designing sophisticated caching strategies in order to improve the content sharing performance. We demonstrate that our caching strategies are capable of reducing the total energy dissipation by as much as ${\text{40}}\%$ . Specifically, the composite betweenness based caching strategy is capable of reducing the energy dissipation of the mesh clients by ${\text{358}}\%$ , compared to its singular betweenness based counterpart. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
W4224105608 | Advances in nanotechnology‐based hair care products applied to hair shaft and hair scalp disorders | Nanotechnology has been intensively applied to the development of novel cosmetic products for hair and scalp care during the last decades. Such a trend is corroborated by the fact that about 19% of the total nanocosmetics registered in the StatNano database are intended for hair and scalp care. Nanotechnology-enabled formulations based on nanoparticles, cyclodextrins, liposomes and nanoemulsions have emerged as novel approaches due to chemical stability and their controlled release. Regarding hair care formulations, nanocarriers can target the hair shaft, hair follicle and scalp. Therefore, they have been used to treat several hair disorders, including dandruff and other hair-damaging conditions.This review addressed the most important nanocarriers applied to hair-related disorders improvement. Furthermore, the application for hair photoprotection and improvement of hair colour duration by nanotechnological formulations is also approached. Besides, we provided an overview of the current scenario of available nano-based commercial hair products and novel patented inventions.From the patent search, the Patent Cooperation Treaty was pointed as the most important depositing agency while the United States of America has been the most depositing country. On the contrary, according to the StatNano database, Brazil stands out in the hair care worldwide market, and it is also the main producer of hair cosmetics based on nanotechnology.As nano-based products offer several advantages over conventional cosmetics, it is expected that in future, there will be more research on nanocarriers applied to hair disorders, as well as commercial products and patent applications.Au cours des dernières décennies, les nanotechnologies ont été intensivement appliquées au développement de nouveaux produits cosmétiques pour le soin des cheveux et du cuir chevelu. Cette tendance est corroborée par le fait qu'environ 19% du nombre total de nano-cosmétiques enregistrés dans la base de données StatNano sont destinés à la fois aux soins des cheveux et du cuir chevelu. Les formulations basées sur les nanoparticules, les cyclodextrines, les liposomes et les nano-émulsions sont devenues de nouvelles approches grâce à l'amélioration de la stabilité chimique des médicaments et des ingrédients actifs cosmétiques et à leur libération contrôlée. En ce qui concerne les formulations de soins capillaires, les nanocarriers peuvent cibler le follicule pileux, la tige des cheveux et du cuir chevelu. Par conséquent, ils ont été utilisés pour traiter plusieurs troubles capillaires, notamment les pellicules et d'autres affections capillaires. Dans cette revue, les nano-carriers les plus importants appliqués à l'amélioration des troubles liés aux cheveux ont été abordés. L'application pour la photoprotection des cheveux et l'amélioration de la durée de la couleur des cheveux par des formulations nanotechnologiques est également abordée. En outre, nous fournissons un aperçu du scénario actuel des produits capillaires commerciaux à base des nanotechnologies disponibles et des nouvelles inventions brevetées. D'après la recherche de brevets, le Traité de coopération en matière de brevets a été désigné comme l'agence de dépôt la plus importante, tandis que les États-Unis d'Amérique ont été le pays le plus déposant. Diversement, le Brésil se distingue sur le marché mondial des soins capillaires et il est aussi le principal producteur de cosmétiques capillaires basés sur les nanotechnologies. Par conséquent, comme les produits à base de nanotechnologies offrent plusieurs avantages par rapport aux cosmétiques conventionnels, on s'attend à ce que les recherches sur les nano-carriers appliqués aux troubles capillaires se multiplient à l'avenir, de même que les produits commerciaux et les demandes de brevets. | [
"Materials Engineering",
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
]
|
10.4171/RLM/712 | A Density Property For Fractional Weighted Sobolev Spaces | In this paper we show a density property for fractional weighted Sobolev spaces. That is, we prove that any function in a fractional weighted Sobolev space can be approximated by a smooth function with compact support. The additional difficulty in this nonlocal setting is caused by the fact that the weights are not necessarily translation invariant. | [
"Mathematics"
]
|
10.1525/collabra.349 | Disgust, Anger, and Aggression: Further Tests of the Equivalence of Moral Emotions | People often report disgust toward moral violations. Some perspectives posit that this disgust is indistinct from anger. Here, we replicate and extend recent work suggesting that disgust and anger toward moral violations are in fact distinct in terms of the situations in which they are activated and their correspondence with aggressive sentiments. We tested three hypotheses concerning emotional responses to moral violations: (1) disgust is associated with lower-cost, indirectly aggressive motives (e. g. , gossip and social exclusion), whereas anger is associated with higher-cost, directly aggressive motives (e. g. , physical violence); (2) disgust is higher toward violations affecting others than it is toward violations affecting the self, and anger is higher toward violations affecting the self than it is toward violations affecting others; and (3) abilities to inflict costs on or withhold benefits from others (measured via physical strength and physical attractiveness, respectively) relate to anger, but not to disgust. These hypotheses were tested in a within-subjects study in which 233 participants came to the lab twice and reported their emotional responses and aggressive sentiments toward self-targeting and other-targeting moral violations. Participants’ upper body strength and physical attractiveness were also measured with a dynamometer and photograph ratings, respectively. The first two hypotheses were supported – disgust (but not anger) was related to indirect aggression whereas anger (but not disgust) was related to direct aggression, and disgust was higher toward other-targeting violations whereas anger was higher toward self-targeting violations. However, physical strength and physical attractiveness were unrelated to anger or disgust or to endorsements of direct or indirect aggression. | [
"The Human Mind and Its Complexity",
"The Social World and Its Interactions"
]
|
10.1088/1757-899X/194/1/012012 | Thermal Stability And Mechanical Properties Of Hpt Processed Cp Ti | A grade 2 commercial pure titanium was processed by high-pressure torsion (HPT) at room temperature to 20 turns. X-ray analysis showed that an ω phase formed during HPT processing but disappeared immediately during 10 minutes post-HPT short-term annealing even at a very low temperature of 473 K. The thermal stability of HPT-processed microstructural evolution was studied by electron backscatter diffraction (EBSD). After short-term annealing at lower temperatures (473 and 673 K), the disc centre had relative higher hardness value than the edge area, and it was found that the centre retained the feature of deformed microstructure whereas the edge showed recovery / recrystallization of the microstructure. Short-term annealing at higher temperatures (873 and 973 K) led to almost uniformly distributed hardness and microstructures in the disc centre and edge areas. Grain structures and hardness measurements indicate complete recrystallization occurred at 873 K. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1016/j.cbpa.2016.06.019 | Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation | Activation of inflammatory gene expression is regulated, among other factors, by post-translational modifications of histone proteins. The most investigated type of histone modifications is lysine acetylations. Histone deacetylases (HDACs) remove acetylations from lysines, thereby influencing (inflammatory) gene expression. Intriguingly, apart from histones, HDACs also target non-histone proteins. The nuclear factor κB (NF-κB) pathway is an important regulator in the expression of numerous inflammatory genes, and acetylation plays a crucial role in regulating its responses. Several studies have shed more light on the role of HDAC 1-3 in inflammation with a particular pro-inflammatory role for HDAC 3. Nevertheless, the HDAC-NF-κB interactions in inflammatory signalling have not been fully understood. An important challenge in targeting the regulatory role of HDACs in the NF-κB pathway is the development of highly potent small molecules that selectively target HDAC iso-enzymes. This review focuses on the role of HDAC 3 in (NF-κB-mediated) inflammation and NF-κB lysine acetylation. In addition, we address the application of frequently used small molecule HDAC inhibitors as an approach to attenuate inflammatory responses, and their potential as novel therapeutics. Finally, recent progress and future directions in medicinal chemistry efforts aimed at HDAC 3-selective inhibitors are discussed. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
223329 | Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window: a randomized, controlled trial | TENSION (efficacy and safety of ThrombEctomy iN Stroke with extended leSION and extended time window: a randomized, controlled trial) strives at providing innovative treatment to patients with severe stroke to reduce the individual and societal burden of death and dependency from stroke. To this end, TENSION is a randomized, controlled, prospective, open label, blinded endpoint (PROBE) trial of thrombectomy in stroke patients with extended ischemic stroke lesions and patients presenting in a late time window, who are currently excluded from available effective treatment approaches. The trial will enroll up to 714 subjects in eight European countries. The primary endpoint is functional outcome at 90 days post-stroke measured by the Modified Rankin Scale. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in ordinal mRS outcomes between treatment groups (“mRS shift analysis”). Outcome evaluation will involve a comprehensive array of clinical and safety parameters, health and socio-economic outcomes including patient reported outcome measures (PROM) for evaluation according to the principles of value-based healthcare. Health economic evaluation with cost-effectiveness analysis will be performed and gender-effects on treatment and outcome will be studied. Trial organization will rely on a network of experienced partners with successful cooperation in previous EU-funded stroke trials. An image core lab will provide central judgement of all images acquired within the trial. Standards of image judgement and intervention will be defined and trial specific training will be provided to all investigators. TENSION addresses a major health problem and will provide evidence for more effective and safer therapeutic intervention for patients with severe stroke resulting in improved guideline development, better individual patient outcomes and beneficial effects for the society at large by reduction of stroke-related costs. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing",
"Individuals, Markets and Organisations"
]
|
10.1177/1065912919853377 | When Do Opponents Of Gay Rights Mobilize Explaining Political Participation In Times Of Backlash Against Liberalism | Existing research suggests that supporters of gay rights have outmobilized their opponents, leading to policy changes in advanced industrialized democracies. At the same time, we observe the diffus. . . | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.1158/1078-0432.CCR-15-1272 | Immunopet With Anti Mesothelin Antibody In Patients With Pancreatic And Ovarian Cancer Before Anti Mesothelin Antibody Drug Conjugate Treatment | Purpose: Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an 89 Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody–drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression. Experimental Design: Before DMOT4039A treatment, patients received 37 MBq 89 Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue. Results: Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUV max of 13. 1 (±7. 5) on PET 4 days postinjection, with 11. 5 (±7. 5) in ( N = 17) pancreatic and 14. 5 (±8. 7) in ( N = 20) ovarian cancer lesions. Within patients, a mean 2. 4-fold (±1. 10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient. Conclusions: With 89 Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. Clin Cancer Res; 22(7); 1642–52. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1021/acscentsci.8b00286 | Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement | Understanding the origins of lipid membrane bilayer rearrangement in response to external stimuli is an essential component of cell biology and the bottom-up design of liposomes for biomedical applications. The enzymes phospholipase C and D (PLC and PLD) both cleave the phosphorus-oxygen bonds of phosphate esters in phosphatidylcholine (PC) lipids. The atomic position of this hydrolysis reaction has huge implications for the stability of PC-containing self-assembled structures, such as the cell wall and lipid-based vesicle drug delivery vectors. While PLC converts PC to diacylglycerol (DAG), the interaction of PC with PLD produces phosphatidic acid (PA). Here we present a combination of small-angle scattering data and all-atom molecular dynamics simulations, providing insights into the effects of atomic-scale reorganization on the supramolecular assembly of PC membrane bilayers upon enzyme-mediated incorporation of DAG or PA. We observed that PC liposomes completely disintegrate in the presence of PLC, as conversion of PC to DAG progresses. At lower concentrations, DAG molecules within fluid PC bilayers form hydrogen bonds with backbone carbonyl oxygens in neighboring PC molecules and burrow into the hydrophobic region. This leads initially to membrane thinning followed by a swelling of the lamellar phase with increased DAG. At higher DAG concentrations, localized membrane tension causes a change in lipid phase from lamellar to the hexagonal and micellar cubic phases. Molecular dynamics simulations show that this destabilization is also caused in part by the decreased ability of DAG-containing PC membranes to coordinate sodium ions. Conversely, PLD-treated PC liposomes remain stable up to extremely high conversions to PA. Here, the negatively charged PA headgroup attracts significant amounts of sodium ions from the bulk solution to the membrane surface, leading to a swelling of the coordinated water layer. These findings are a vital step toward a fundamental understanding of the degradation behavior of PC lipid membranes in the presence of these clinically relevant enzymes, and toward the rational design of diagnostic and drug delivery technologies for phospholipase-dysregulation-based diseases. | [
"Condensed Matter Physics",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences"
]
|
10.1115/GT2013-95594 | Residence Time Distribution In A Swirling Flow At Non Reacting Reacting And Steam Diluted Conditions | Residence time distributions in a swirling, premixed combustor flow are determined by means of tracer experiments and a reactor network model. The measurements were conducted at nonreacting, reacting, and steam-diluted reacting conditions for steam contents of up to 30% of the air mass flow. The tracer distribution was obtained from the light scattering of seeding particles employing the quantitative light sheet technique (QLS). At steady operating conditions, a positive step of particle feed was applied, yielding cumulative distribution functions (CDF) for the tracer response. The shape of the curve is characteristic for the local degree of mixedness. Fresh and recirculating gases were found to mix rapidly at nonreacting and highly steam-diluted conditions, whereas mixing was more gradual at dry reacting conditions. The instantaneous mixing near the burner outlet is related to the presence of a large-scale helical structure, which was suppressed at dry reacting conditions. Zones of similar mixing time scales, such as the recirculation zones, are identified. The CDF curves in these zones are reproduced by a network model of plug flow and perfectly mixed flow reactors. Reactor residence times and inlet volume flow fractions obtained in this way provide data for kinetic network models. | [
"Physical and Analytical Chemical Sciences",
"Products and Processes Engineering"
]
|
US 2017/0055838 W | SOUND INSULATION PANELS HAVING HIGH INTERLAYER THICKNESS FACTORS | A multiple layer panel having improved sound insulation is disclosed. The multiple layer panel comprises a first rigid substrate having a first thickness H3, a second rigid substrate having a second thickness H1, wherein H3 ≤ H1, and a multiple layer acoustic interlayer having a thickness H2 between the first and second rigid substrates. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
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