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10.1371/journal.pone.0134219
Microbial ligand costimulation drives neutrophilic steroid-refractory asthma
Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these micro-bial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.
[ "Immunity, Infection and Immunotherapy", "Physiology in Health, Disease and Ageing" ]
10.1159/000459635
Early Programming Of Obesity Throughout The Life Course A Metabolomics Perspective
Background: Over the last decades, research on early life risk factors for obesity and its comorbidities in early life has gained attention within the field of de
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1214/14-AAP1048
Optimal Scaling For The Transient Phase Of The Random Walk Metropolis Algorithm The Mean Field Limit
We consider the random walk Metropolis algorithm on $\mathbb{R}^{n}$ with Gaussian proposals, and when the target probability measure is the $n$-fold product of a one-dimensional law. In the limit $n\to\infty$, it is well known (see [ Ann. Appl. Probab. 7 (1997) 110–120]) that, when the variance of the proposal scales inversely proportional to the dimension $n$ whereas time is accelerated by the factor $n$, a diffusive limit is obtained for each component of the Markov chain if this chain starts at equilibrium. This paper extends this result when the initial distribution is not the target probability measure. Remarking that the interaction between the components of the chain due to the common acceptance/rejection of the proposed moves is of mean-field type, we obtain a propagation of chaos result under the same scaling as in the stationary case. This proves that, in terms of the dimension $n$, the same scaling holds for the transient phase of the Metropolis–Hastings algorithm as near stationarity. The diffusive and mean-field limit of each component is a diffusion process nonlinear in the sense of McKean. This opens the route to new investigations of the optimal choice for the variance of the proposal distribution in order to accelerate convergence to equilibrium (see [Optimal scaling for the transient phase of Metropolis–Hastings algorithms: The longtime behavior Bernoulli (2014) To appear]).
[ "Mathematics", "Computer Science and Informatics" ]
10.1039/C1CC11985K
Reversible Pressure Induced Amorphization Of A Zeolitic Imidazolate Framework Zif 4
We report the reversible pressure-induced amorphization of a zeolitic imidazolate framework (ZIF-4, [Zn(Im)2]). This occurs irrespective of pore occupancy and takes place via a novel high pressure phase (ZIF-4-I) when solvent molecules are present in the pores. A significant reduction in bulk modulus upon framework evacuation is also observed for both ZIF-4 and ZIF-4-I.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1038/s41467-017-01374-x
High-frequency recombination between members of an LTR retrotransposon family during transposition bursts
Retrotransposons containing long terminal repeats (LTRs) form a substantial fraction of eukaryotic genomes. The timing of past transposition can be estimated by quantifying the accumulation of mutations in initially identical LTRs. This way, retrotransposons are divided into young, potentially mobile elements, and old that moved thousands or even millions of years ago. Both types are found within a single retrotransposon family and it is assumed that the old members will remain immobile and degenerate further. Here, we provide evidence in Arabidopsis that old members enter into replication/transposition cycles through high rates of intra-family recombination. The recombination occurs pairwise, resembling the formation of recombinant retroviruses. Thus, each transposition burst generates a novel progeny population of chromosomally integrated LTR retrotransposons consisting of pairwise recombination products produced in a process comparable the sexual exchange of genetic information. Our observations provide an explanation for the reported high rates of sequence diversification in retrotransposons.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1021/nl502837d
Friction of water on graphene and hexagonal boron nitride from Ab initio methods: Very different slippage despite very similar interface structures
Friction is one of the main sources of dissipation at liquid water/solid interfaces. Despite recent progress, a detailed understanding of water/solid friction in connection with the structure and energetics of the solid surface is lacking. Here, we show for the first time that ab initio molecular dynamics can be used to unravel the connection between the structure of nanoscale water and friction for liquid water in contact with graphene and with hexagonal boron nitride. We find that although the interface presents a very similar structure between the two sheets, the friction coefficient on boron nitride is ∼3 times larger than that on graphene. This comes about because of the greater corrugation of the energy landscape on boron nitride arising from specific electronic structure effects. We discuss how a subtle dependence of the friction on the atomistic details of a surface, which is not related to its wetting properties, may have a significant impact on the transport of water at the nanoscale, with implications for the development of membranes for desalination and for osmotic power harvesting.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
W1823605548
Synergistic effects of geographical strain, temperature and larval food on insecticide tolerance in Callosobruchus maculatus (F.)
This study investigated the multifactorial interaction of various environmental factors including geographical strain (Brazil, Cameroon and Yemen strains), temperature, dose and larval food (cowpea and mungbean) on the response of Callosobruchus maculatus adult to insecticide. All the main factors, their two-way interactions and the four-way interaction had significant effects on C. maculatus response to malathion (an organophosphate insecticide). However, the three-way interactions were not statistically significant (except strain × food × dose, P = 0.002). The Brazil strain was the most responsive to temperature irrespective of the larval food type. The impact of food type differs from one strain to the other; for instance, the food that imparts higher tolerance in a strain might reduce the tolerance in another. Likewise, the hierarchy of tolerance among the cowpea-reared strains (Brazil > Cameroon > Yemen) was totally different from that of the mungbean-reared strains (Cameroon > Yemen > Brazil). The reasons for these differences were discussed in the light of their impact on C. maculatus management. Both the management of C. maculatus and development of resistance could be complex; hence, the states of a variety of environmental factors need to be considered. This is necessary to maximize management success of this bruchid, especially in tropical/subtropical developing countries.
[ "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Biotechnology and Biosystems Engineering" ]
US 2019/0038462 W
METHODS AND APPARATUSES FOR PROVIDING INPUT FOR HEAD-WORN IMAGE DISPLAY DEVICES
An apparatus for use with an image display device configured for head-worn by a user, includes: a screen; and a processing unit configured to assign a first area of the screen to sense finger-action of the user; wherein the processing unit is configured to generate an electronic signal to cause a change in a content displayed by the display device based on the finger-action of the user sensed by the assigned first area of the screen of the apparatus.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1039/c8sm02157k
A stochastic model for bacteria-driven micro-swimmers
We derive analytical expressions for the diffusion coefficient and the chemotactic drift velocity of bacteria-driven micro-swimmers.
[ "Mathematics", "Physical and Analytical Chemical Sciences" ]
10.1109/JPROC.2016.2597152
Spintronic Nanodevices For Bioinspired Computing
Bioinspired hardware holds the promise of low-energy, intelligent, and highly adaptable computing systems. Applications span from automatic classification for big data management, through unmanned vehicle control, to control for biomedical prosthesis. However, one of the major challenges of fabricating bioinspired hardware is building ultrahigh-density networks out of complex processing units interlinked by tunable connections. Nanometer-scale devices exploiting spin electronics (or spintronics) can be a key technology in this context. In particular, magnetic tunnel junctions (MTJs) are well suited for this purpose because of their multiple tunable functionalities. One such functionality, nonvolatile memory, can provide massive embedded memory in unconventional circuits, thus escaping the von-Neumann bottleneck arising when memory and processors are located separately. Other features of spintronic devices that could be beneficial for bioinspired computing include tunable fast nonlinear dynamics, controlled stochasticity, and the ability of single devices to change functions in different operating conditions. Large networks of interacting spintronic nanodevices can have their interactions tuned to induce complex dynamics such as synchronization, chaos, soliton diffusion, phase transitions, criticality, and convergence to multiple metastable states. A number of groups have recently proposed bioinspired architectures that include one or several types of spintronic nanodevices. In this paper, we show how spintronics can be used for bioinspired computing. We review the different approaches that have been proposed, the recent advances in this direction, and the challenges toward fully integrated spintronics complementary metal–oxide–semiconductor (CMOS) bioinspired hardware.
[ "Condensed Matter Physics", "Computer Science and Informatics", "Materials Engineering" ]
184637
Savanna water and carbon fluxes modelling integrating earth observation data
The aim of SWATCH is to develop a unique information system for quantifying savanna water use and biomass production on a regional scale, with the ultimate objective of supporting decision-making processes. This effort directly addresses the European H2020 priorities of sustainable rural development and food security. Savannas are among the most complex, variable and extensive agrosilvopastoral systems on Earth (~20%). One fifth of the world's population depend upon them, although they are extremely vulnerable to changes in land use and climate. These changes affect not only ecosystem functioning, but also the land-atmosphere linkages and regional carbon cycle, in ways still unknown. Since savannas are greatly influenced by human activities, private/institutional practices play a key role in their conservation. The integration of Earth Observation data into process-based models will enable us to map the evolution of the ecosystem health, improving their management, productivity and resilience. However, to map savanna fluxes, besides the mechanistic understanding of how the climate (dry periods) and the canopy structure (patched multiple canopy layers) interact with land-atmospheric processes, robust techniques to upscale the ecosystem parameters and fluxes over space and time are needed. This project intends to bridge this gap and contribute to: 1) a better mechanistic understanding of savanna water/energy/carbon fluxes, using long-term eddy covariance and ground measurements 2) more accurately modelling these fluxes on a regional scale with different-scale EO data 3) the development of an operational information system to be integrated into decision-making processes, evaluating a pilot experience located over dehesa (Spanish productive savanna).The outgoing phase with Prof. Baldocchi's group (UC Berkeley, USA) intends to cover first and second objectives, while the third one will be address on the return phase, with Dr. Gonzalez-Dugo's group (IFAPA, Spain).
[ "Earth System Science", "Environmental Biology, Ecology and Evolution", "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1371/journal.pgen.1008905
Active transcription and Orc1 drive chromatin association of the AAA+ ATPase Pch2 during meiotic G2/prophase
Pch2 is an AAA+ protein that controls DNA break formation, recombination and checkpoint signaling during meiotic G2/prophase. Chromosomal association of Pch2 is linked to these processes, and several factors influence the association of Pch2 to euchromatin and the specialized chromatin of the ribosomal (r)DNA array of budding yeast. Here, we describe a comprehensive mapping of Pch2 localization across the budding yeast genome during meiotic G2/prophase. Within non-rDNA chromatin, Pch2 associates with a subset of actively RNA Polymerase II (RNAPII)-dependent transcribed genes. Chromatin immunoprecipitation (ChIP)-A nd microscopy-based analysis reveals that active transcription is required for chromosomal recruitment of Pch2. Similar to what was previously established for association of Pch2 with rDNA chromatin, we find that Orc1, a component of the Origin Recognition Complex (ORC), is required for the association of Pch2 to these euchromatic, transcribed regions, revealing a broad connection between chromosomal association of Pch2 and Orc1/ORC function. Ectopic mitotic expression is insufficient to drive recruitment of Pch2, despite the presence of active transcription and Orc1/ORC in mitotic cells. This suggests meiosisspecific 'licensing' of Pch2 recruitment to sites of transcription, and accordingly, we find that the synaptonemal complex (SC) component Zip1 is required for the recruitment of Pch2 to transcription-associated binding regions. Interestingly, Pch2 binding patterns are distinct from meiotic axis enrichment sites (as defined by Red1, Hop1, and Rec8). Inactivating RNAPII-dependent transcription/Orc1 does not lead to effects on the chromosomal abundance of Hop1, a known chromosomal client of Pch2, suggesting a complex relationship between SC formation, Pch2 recruitment and Hop1 chromosomal association. We thus report characteristics and dependencies for Pch2 recruitment to meiotic chromosomes, and reveal an unexpected link between Pch2, SC formation, chromatin and active transcription.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
312458
LANGUAGE–PHILOLOGY–CULTURE: Arab Cultural Semantics in Transition
This project aims to study: • the semantic development of the vocabulary of the Arabic language, • philological discourses on the semantic changes in the language in the classical Arabic philological tradition (8th-10th centuries A.D.), and • the impact of Arabic philology in the wider historical and cultural context of the Judaeo-Arab neo-classical heritage (12th-13th centuries A.D.) and Christian-Arab intellectual history on the eve of modernity (19th century A.D.). The project will explore the universal cultural significance and the pivotal role of language consciousness in the history of Arab culture. It will introduce a new dimension into the existing research on the Arabic language and Arabic philology, which until now have been studied without any comprehensive cultural and social contextualisation. The project will focus on the process of the transmission of Arabic poetry, which provides detailed evidence of the development of Arabic philological thought and its universal significance for the theological, philosophical, historical and linguistic discourses of Arab intellectual history. This project will document the transmission of early Arabic poetry and analyse its vocabulary in a systematic way for the first time. For this purpose it will create an Analytical Database of Arabic Poetry. This publicly accessible database will represent a ground-breaking contribution to European research on the Arabic language and the Arabic philological heritage, which so far lacks even such fundamental tools as an etymological dictionary of the Arabic language or a complete dictionary of Classical Arabic. The database will implement comprehensive analytical tools and will serve as a reference work for wider research on Arabic literature, history and culture. Thus, the project will create an integrative research platform for the history and semantics of the Arabic language—a subject indispensable for understanding the foundations of Arab culture past and present.
[ "Texts and Concepts", "The Study of the Human Past", "Studies of Cultures and Arts" ]
10.1242/jcs.162305
CRL4RBBP7 is required for efficient CENP-A deposition at centromeres
The mitotic spindle drives chromosome movement during mitosis and attaches to chromosomes at dedicated genomic loci named centromeres. Centromeres are epigenetically specified by their histone composition with the presence of the histone H3 variant CENP-A, which is regulated during the cell cycle by its dynamic expression and localization. Here, we combined biochemical methods and quantitative imaging approaches to investigate a novel function of CUL4-RING E3 ubiquitin ligases (CRL4) in regulating CENP-A dynamics. We found that the core components CUL4 and DDB1 are required for centromeric loading of CENP-A, but do not influence CENP-A maintenance or pre-nucleosomal CENP-A levels. Interestingly, we identified RBBP7 as a substrate-specific CRL4 adaptor required for this process, in addition to its role in binding and stabilizing soluble CENP-A. Our data thus suggest that CRL4RBBP7 may regulate mitosis by promoting ubiquitin-dependent loading of newly synthesized CENP-A during the G1 phase of the cell cycle.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1515/opth-2019-0004
Spatial analysis of new testament textual emendations utilizing confusion distances
Before the interpretation of any text can start, the original wording of the text itself must be critically established. Conventionally, this is done following qualitative criteria. This article, however, explores the application of spatial analyses to New Testament textual criticism by demonstrating how the Levenshtein edit distance could be adapted to calculate confusion distances for variant readings in New Testament manuscripts, i. e. the possibility that a (combination of) letter(s) is confused by another (combination of) letter(s). Subsequently the outcomes are translated to Euclidian space using classical Multi-Dimensional Scaling, which enables visualisation and spatial analyses (in this case not related to geographical space). The article focuses on the data preparation and algorithm to make the data suitable for spatial analyses, thus providing the New Testament textual critic with new analytical tools.
[ "Computer Science and Informatics", "Texts and Concepts" ]
10.1145/2714566
A Survey On Low Power Techniques With Emerging Technologies From Devices To Systems
Nowadays, power consumption is one of the main limitations of electronic systems. In this context, novel and emerging devices provide new opportunities to extend the trend toward low-power design. In this survey article, we present a transversal survey on energy-efficient techniques ranging from devices to architectures. The actual trends of device research, with fully depleted planar devices, tri-gate geometries, and gate-all-around structures, allows us to reach an increasingly higher level of performance while reducing the associated power. In addition, beyond the simple device property enhancements, emerging devices also lead to innovations at the circuit and architectural levels. In particular, devices whose properties can be tuned through additional terminals enable a fine and dynamic control of device threshold. They also enable designers to realize logic gates and to implement power-related techniques in a compact way unreachable to standard technologies. These innovations reduce power consumption at the gate level and unlock new means of actuation in architectural solutions like adaptive voltage and frequency scaling.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1117/12.2289859
Ge Rich Sige Photonic Integrated Circuits For Mid Ir Spectroscopy
Recent works towards the development of Ge-rich SiGe photonic integrated circuits will be presented, such as the demonstration of low-loss waveguides and ultra-wideband Mach Zehnder interferometer from 5. 5 to 8. 6 μm wavelength, as well as the first steps towards the realization of efficient wideband optical sources.
[ "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering" ]
GB 0226786 A
Water deflector for decking
A deck 6, attached to a wall 1 of a building, comprises a plurality of boards 6 mounted onto a framework 2, 5 fixed 3 to the wall, and including an elongate member 7 attached to the upper surface of the deck and adjacent the wall so as to deflect water, especially rain water 10, from the wall. The member 7 is preferably attached to the deck by plastics wedges 8 having on their lower and upper faces an array of ribbed and recessed areas (Fig 2, not shown), the ribbed areas enhancing the grip between the wedges and both the deck boards and the elongate member, and the recessed areas providing fixing surfaces.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1007/s10851-016-0641-0
Locally Adaptive Frames in the Roto-Translation Group and Their Applications in Medical Imaging
Locally adaptive differential frames (gauge frames) are a well-known effective tool in image analysis, used in differential invariants and PDE-flows. However, at complex structures such as crossings or junctions, these frames are not well defined. Therefore, we generalize the notion of gauge frames on images to gauge frames on data representations U: Rd⋊ Sd-1→ R defined on the extended space of positions and orientations, which we relate to data on the roto-translation group SE(d), d= 2 , 3. This allows to define multiple frames per position, one per orientation. We compute these frames via exponential curve fits in the extended data representations in SE(d). These curve fits minimize first- or second-order variational problems which are solved by spectral decomposition of, respectively, a structure tensor or Hessian of data on SE(d). We include these gauge frames in differential invariants and crossing-preserving PDE-flows acting on extended data representation U and we show their advantage compared to the standard left-invariant frame on SE(d). Applications include crossing-preserving filtering and improved segmentations of the vascular tree in retinal images, and new 3D extensions of coherence-enhancing diffusion via invertible orientation scores.
[ "Mathematics", "Computer Science and Informatics" ]
Q6725547
Implementation of an innovative product in the form of a smart fibre switch on the market.
The product that will be created during the implementation of the project will be an intelligent switch with a controller and software for passporting fiber optic networks, detecting ports and detecting failure sites. The product technically and functionally has the characteristics of product innovation. The product by combining commonly used light wave propagation technology (i.e. visible light) in fiber optic networks and widely available optical components (splitters) will allow for new functionalities, previously unavailable in switches available on the market. The implementation of additional optical signals (which acts as an information signal) in the main transmission track allows to create an innovative solution for connection detection, monitoring and process automation. Allows you to create real-time connection maps – passporting (so far, in most cases available by manual input of data). At the same time, remote solution used, fully automated detection of the occurrence of a failure site, and reveals any malfunctions in the operation of the optical network, which affects the time and human resources required to resolve failures in the case of standard crossings.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
EP 2018051646 W
PROCESS FOR FORMING SHAPED ARTICLES COMPRISING CARBON NANOTUBES
A process for manufacturing shaped articles comprising carbon nanotubes comprising the steps of supplying carbon nanotubes in an acidic liquid comprising at least one acid, the at least one acid having a Hammett acidity function less than that of 100% sulfuric acid, the at least one acid having a Hammett acidity function equal or more than that of 90% sulfuric acid, and shaping the acidic liquid comprising carbon nanotubes into a shaped article.
[ "Materials Engineering", "Synthetic Chemistry and Materials" ]
W2372473666
On the physico-chemical monitoring and evaluation of the water environment for lenok and burbot aquatic germplasm resources of Pangu River reserve,Heilongjiang,China
The article takes it as its target to report its authors'investigation and physico-chemical monitoring and evaluation results of the water environment situation for lenok and burbot aquatic germplasm resources of Pangu River reserve, Heilongjiang, China. As is known, the natural reserve of Pangu River aquatic germplasm resources is one of the famous natural reserves for cold-water fish growing and breeding.Needless to say, it is of great significance to pursue its water-quality changing situations and protect its water quality from being polluted and contaminated through effective protection and observation.It is just for this goal that there is a great need for us to master the skills to test the physico-chemical properties of the river water.In this article, we have tested and analyzed over 30 indexes of the water and 13 metal elements existing in the sediments and fishes through on-site investigations.According to the second standard national surface water protection regulation, we have assessed the quality of the river water in accordance with the comprehensive evaluation indexes and the evaluation formula for the organic pollutants.The results of our investigation and analysis indicate that Pangu River, which is located in the north of Tahe County of Daxinganling area, with its geographic situations in the coordinates 52°09'-53°22'N, 123°19'-124°49'E.Our investigation and analysis results show that the water quality remains clean and clear, high and pure in the original state.The comprehensive evaluation indexes show that the water quality comprehensive evaluation index is 0.27 and the organic pollution comprehensive evaluation index is 0.96, which suggests that the water qualities are in full conformity with the state water protection standard level.The reach can provide us with a good condition for the growth and reproduction of cold-water fishes, such as lenok and burbot.
[ "Earth System Science", "Environmental Biology, Ecology and Evolution", "Physical and Analytical Chemical Sciences" ]
10.1109/EMBC.2014.6944568
Closed Form Solution Of The Convolution Integral In The Magnetic Resonance Dispersion Model For Quantitative Assessment Of Angiogenesis
Prostate cancer (PCa) diagnosis and treatment is still limited due to the lack of reliable imaging methods for cancer localization. Based on the fundamental role played by angiogenesis in cancer growth and development, several dynamic contrast enhanced (DCE) imaging methods have been developed to probe tumor angiogenic vasculature. In DCE magnetic resonance imaging (MRI), pharmacokinetic modeling allows estimating quantitative parameters related to the physiology underlying tumor angiogenesis. In particular, novel magnetic resonance dispersion imaging (MRDI) enables quantitative assessment of the microvascular architecture and leakage, by describing the intravascular dispersion kinetics of an extravascular contrast agent with a dispersion model. According to this model, the tissue contrast concentration at each voxel is given by the convolution between the intravascular concentration, described as a Brownian motion process according to the convective-dispersion equation, with the interstitium impulse response, represented by a mono-exponential decay, and describing the contrast leakage in the extravascular space. In this work, an improved formulation of the MRDI method is obtained by providing an analytical solution for the convolution integral present in the dispersion model. The performance of the proposed method was evaluated by means of dedicated simulations in terms of estimation accuracy, precision, and computation time. Moreover, a preliminary clinical validation was carried out in five patients with proven PCa. The proposed method allows for a reduction by about 40% of computation time without any significant change in estimation accuracy and precision, and in the clinical performance.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physical and Analytical Chemical Sciences", "Mathematics" ]
10.3847/1538-4357/ab1d4a
The Case of H<inf>2</inf>C<inf>3</inf>O Isomers, Revisited: Solving the Mystery of the Missing Propadienone
To date, two isomers of H2C3O have been detected, namely, propynal (HCCCHO) and cylclopropenone (c-H2C3O). A third, propadienone (CH2CCO), has thus far eluded observers despite the fact that it is the lowest in energy of the three. This previously noted result is in contradiction to the minimum energy principle, which posits that the abundances of isomers in interstellar environments can be predicted based on their relative stabilities and suggests, rather, the importance of kinetic over thermodynamic effects in explaining the role of such species. Here, we report results of ab initio quantum chemical calculations of the reaction between H and (a) HC3O, (b) H2C3O (both propynal and propadienone), and (c) CH2CHCO. We have found that, among all possible reactions between atomic hydrogen and either propadienone or propynal, only the destruction of propadienone is barrierless and exothermic. That this destruction pathway is indeed behind the nondetection of CH2CCO is further suggested by our finding that the product of this process, the radical CH2CHCO, can subsequently react barrierlessly with H to form propenal (CH2CHCHO) which has, in fact, been detected in regions where the other two H2C3O isomers are observed. Thus, these results not only shed light on a previously unresolved astrochemical mystery, but also further highlight the importance of kinetics in understanding the abundances of interstellar molecules.
[ "Physical and Analytical Chemical Sciences", "Universe Sciences" ]
10.5194/cp-13-1049-2017
The C&lt;sub&gt;32&lt;/sub&gt; alkane-1,15-diol as a proxy of late Quaternary riverine input in coastal margins
. The study of past sedimentary records from coastal margins allows us to reconstruct variations in terrestrial input into the marine realm and to gain insight into continental climatic variability. There are numerous organic proxies for tracing terrestrial input into marine environments but none that strictly reflect the input of river-produced organic matter. Here, we test the fractional abundance of the C32 alkane 1,15-diol relative to all 1,13- and 1,15-long-chain diols (FC32 1, 15) as a tracer of input of river-produced organic matter in the marine realm in surface and Quaternary (0–45 ka) sediments on the shelf off the Zambezi and nearby smaller rivers in the Mozambique Channel (western Indian Ocean). A Quaternary (0–22 ka) sediment record off the Nile River mouth in the eastern Mediterranean was also studied for long-chain diols. For the Mozambique Channel, surface sediments of sites most proximal to Mozambique rivers showed the highest F1, 15 − C32 (up to 10 %). The sedimentary record shows high (15–35 %) pre-Holocene F1, 15 − C32 and low (< 10 %) Holocene F1, 15 − C32 values, with a major decrease between 18 and 12 ka. F1, 15 − C32 is significantly correlated (r2 =  0. 83, p < 0. 001) with the branched and isoprenoid tetraether (BIT) index, a proxy for the input of soil and river-produced organic matter in the marine environment, which declines from 0. 25 to 0. 60 for the pre-Holocene to < 0. 10 for the Holocene. This decrease in both FC32 1, 15 and the BIT is interpreted to be mainly due to rising sea level, which caused the Zambezi River mouth to become more distal to our study site, thereby decreasing riverine input at the core location. Some small discrepancies are observed between the records of the BIT index and FC32 1, 15 for Heinrich Event 1 (H1) and the Younger Dryas (YD), which may be explained by a change in soil sources in the catchment area rather than a change in river influx. Like for the Mozambique Channel, a significant correlation between FC32 1, 15 and the BIT index (r2 =  0. 38, p < 0. 001) is observed for the eastern Mediterranean Nile record. Here also, the BIT index and FC32 1, 15 are lower in the Holocene than in the pre-Holocene, which is likely due to the sea level rise. In general, the differences between the BIT index and FC32 1, 15 eastern Mediterranean Nile records can be explained by the fact that the BIT index is not only affected by riverine runoff but also by vegetation cover with increasing cover leading to lower soil erosion. Our results confirm that FC32 1, 15 is a complementary proxy for tracing riverine input of organic matter into marine shelf settings, and, in comparison with other proxies, it seems not to be affected by soil and vegetation changes in the catchment area.
[ "Earth System Science" ]
10.1093/beheco/art091
An evolutionary approach to change of status-fertility relationship in human fertility transition
The change in benefits of high socioeconomic status to fertility in humans during the demographic transition from high to low fertility has interested both demographers and evolutionary biologists. Evolutionary analyses add to demographic analyses by considering also males and status-related differential in male mating success, but they have been limited to time cross-sections and have not linked this differential to differentials in other determinants of male fertility. We use life-history records of males (n = 3791) entering marriage market before (1810s-1880s) and during (1890s-1960s) the Finnish fertility transition to investigate associations between socioeconomic status and chance and timing of marriage, choice for spouse, and lifetime fertility. Low status invariantly brought a lower marriage chance throughout these 160 years, which partly explained why ever-married high-status men lost advantage at early marriage when the system of achieving a high status shifted from inheritance to self-effort. The loss, coupled with assortative mating by age, promoted disappearance of differential in wife's age at marriage and thus, disappearance of differential in fertility between ever-married high- and low-status men in the Finnish fertility transition. Consequently, among all men (married and unmarried), status-related differential in lifetime fertility - not selection coefficient - declined over the transition. This study is among the first to show the interrelated dynamics of status-related differentials in male mating and reproductive traits; by doing so, it contributes to an evolutionary understanding of change of status-fertility relationship in human fertility transition and confirms continuing phenotypic selection on male status/wealth in modern societies.
[ "Environmental Biology, Ecology and Evolution", "Human Mobility, Environment, and Space" ]
10.1021/acsmacrolett.5b00608
Amphiphilic Polymer Conetworks Based on End-Linked "core-First" Star Block Copolymers: Structure Formation with Long-Range Order
Amphiphilic polymer conetworks are cross-linked polymers that swell both in water and in organic solvents and can phase separate on the nanoscale in the bulk or in selective solvents. To date, however, this phase separation has only been reported with short-range order, characterized by disordered morphologies. We now report the first example of amphiphilic polymer conetworks, based on end-linked "core-first" star block copolymers, that form a lamellar phase with long-range order. These mesoscopically ordered systems can be produced in a simple fashion and exhibit significantly improved mechanical properties.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1098/rspb.2017.0335
What shapes the continuum of reproductive isolation? Lessons from Heliconius butterflies
The process by which species evolve can be illuminated by investigating barriers that limit gene flow between taxa. Recent radiations, such as Heliconius butterflies, offer the opportunity to compare isolation between pairs of taxa at different stages of ecological, geographical, and phylogenetic divergence. Here, we report a comparative analysis of existing and novel data in order to quantify the strength and direction of isolating barriers within a well-studied clade of Heliconius . Our results highlight that increased divergence is associated with the accumulation of stronger and more numerous barriers to gene flow. Wing pattern is both under natural selection for Müllerian mimicry and involved in mate choice, and therefore underlies several isolating barriers. However, pairs which share a similar wing pattern also display strong reproductive isolation mediated by traits other than wing pattern. This suggests that, while wing pattern is a key factor for early stages of divergence, it may become facultative at later stages of divergence. Additional factors including habitat partitioning, hybrid sterility, and chemically mediated mate choice are associated with complete speciation. Therefore, although most previous work has emphasized the role of wing pattern, our comparative results highlight that speciation is a multi-dimensional process, whose completion is stabilized by many factors.
[ "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
679186
Foraging Decision Making in the Real World – revealed from a bat’s point of view by on-board miniature sensors
How animals make decisions in the wild is an open key-question in biology. Our lack of knowledge results from a technological gap – the difficulty to track animals over long periods while monitoring their behaviour; and from a conceptual gap – how to identify animals’ decision-points outdoors? We suggest applying our innovative on-board miniature sensors, to study decision making in the wild. We focus on one of the most fundamental contexts of decision making – foraging for food. We will study bats, which constitute over 20% of mammalian species and are extremely diverse, enabling to examine different aspects of decision making. Importantly, echolocating bats emit sound to perceive their environment, allowing us to infer their behavior (attacks on prey and interactions with conspecifics) via sound recording. Our miniature sensors include a GPS and an ultrasonic microphone, which enables us to reveal not only bats’ movements, but also their behavior and accordingly the factors underlying their decisions. We will study three bat species to elucidate different aspects of foraging decisions: (1) How does animal sociality facilitate decision making? We have developed a system to monitor an entire colony including all conspecific-interactions when bats are in the roost or foraging outside. (2) How do animals weigh current input against previous experience? We will study a bat that must nightly search large areas over sea to find food. (3) How flexible are animal decisions? We will manipulate the natural environment of specific individuals to study how they adjust their foraging. Our results will have far-reaching implications in many fields, from animal conservation to robotics. The operational and technical difficulty of performing controlled manipulations in the wild drives most disciplines to perform experiments exclusively in artificial laboratory conditions. Our approach opens new opportunities to conduct controlled studies in the natural environment.
[ "Environmental Biology, Ecology and Evolution", "Biotechnology and Biosystems Engineering", "Computer Science and Informatics" ]
10.3389/fcell.2018.00100
The Warburg effect in endothelial cells and its potential as an anti-angiogenic target in cancer
Endothelial cells (ECs) make up the lining of our blood vessels and they ensure optimal nutrient and oxygen delivery to the parenchymal tissue. In response to oxygen and/or nutrient deprivation, ECs become activated and sprout into hypo-vascularized tissues forming new vascular networks in a process termed angiogenesis. New sprouts are led by migratory tip cells and extended through the proliferation of trailing stalk cells. Activated ECs rewire their metabolism to cope with the increased energetic and biosynthetic demands associated with migration and proliferation. Moreover, metabolic signaling pathways interact and integrate with angiogenic signaling events. These metabolic adaptations play essential roles in determining EC fate and function, and are perturbed during pathological angiogenesis, as occurs in cancer. The angiogenic switch, or the growth of new blood vessels into an expanding tumor, increases tumor growth and malignancy. Limiting tumor angiogenesis has therefore long been a goal for anticancer therapy but the traditional growth factor targeted anti-angiogenic treatments have met with limited success. In recent years however, it has become increasingly recognized that focusing on altered tumor EC metabolism provides an attractive alternative anti-angiogenic strategy. In this review, we will describe the EC metabolic signature and how changes in EC metabolism affect EC fate during physiological sprouting, as well as in the cancer setting. Then, we will discuss the potential of targeting EC metabolism as a promising approach to develop new anti-cancer therapies.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.5194/acp-19-4741-2019
Cloud condensation nuclei activity of six pollenkitts and the influence of their surface activity
The role of surfactants in governing water interactions of atmospheric aerosols has been a recurring topic in cloud microphysics for more than two decades. Studies of detailed surface thermodynamics are limited by the availability of aerosol samples for experimental analysis and incomplete validation of various proposed Köhler model frameworks for complex mixtures representative of atmospheric aerosol. Pollenkitt is a viscous material that coats grains of pollen and plays important roles in pollen dispersion and plant reproduction. Previous work suggests that it may also be an important contributor to pollen water uptake and cloud condensation nuclei (CCN) activity. The chemical composition of pollenkitt varies between species but has been found to comprise complex organic mixtures including oxygenated, lipid, and aliphatic functionalities. This mix of functionalities suggests that pollenkitt may display aqueous surface activity, which could significantly impact pollen interactions with atmospheric water. Here, we study the surface activity of pollenkitt from six different species and its influence on pollenkitt hygroscopicity. We measure cloud droplet activation and concentration-dependent surface tension of pollenkitt and its mixtures with ammonium sulfate salt. Experiments are compared to predictions from several thermodynamic models, taking aqueous surface tension reduction and surfactant surface partitioning into account in various ways. We find a clear reduction of surface tension by pollenkitt in aqueous solution and evidence for impact of both surface tension and surface partitioning mechanisms on cloud droplet activation potential and hygroscopicity of pollenkitt particles. In addition, we find indications of complex nonideal solution effects in a systematic and consistent dependency of pollenkitt hygroscopicity on particle size. The impact of pollenkitt surface activity on cloud microphysics is different from what is observed in previous work for simple atmospheric surfactants and more resembles recent observations for complex primary and secondary organic aerosol, adding new insight to our understanding of the multifaceted role of surfactants in governing aerosol-water interactions. We illustrate how the explicit characterization of pollenkitt contributions provides the basis for modeling water uptake and cloud formation of pollen and their fragments over a wide range of atmospheric conditions.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
W2002626578
Metal pollution status in Zhelin Bay surface sediments inferred from a sequential extraction technique, South China Sea
Surface sediments collected from Zhelin Bay, the largest mariculture base of eastern Guangdong Province, were analyzed for total metal concentrations and chemical speciation. The results demonstrated that the average total concentration (mg/kg) ranges were 36.7-65.8 (Pb), 53.8-98.8 (Cr), 39.0-87.1 (Ni), 50.9-144.5 (Cu), and 175.0-251.2 (Zn), which were clearly higher with respect to their corresponding benchmark values. The predominant speciation of Pb was reducible and comprised a residual fraction, whereas a major portion (57.6-95.4%) of Cr, Ni, Cu, and Zn was strongly associated with the residual fractions. Taking as a whole, surface sediments of Zhelin Bay had a 21% probability of toxicity based on the mean effects range-median quotient.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
888538
Development and application of hybrid joining in lightweight integral aircraft structures
The main objective of the DAHLIAS project is to optimise hybrid joining (Refill Friction Stir Spot Welding, RFSSW, with an adhesive sealant bond) for application in aircraft structures. RFSSW is a solid-state joining technology especially applicable to lightweight alloys in similar and dissimilar configurations. The process has been successfully applied to difficult-to-weld and non-weldable alloys and is considered a potential replacement of mechanical fastening. Overlap joints in aircraft structures require the use of sealants for corrosion protection reasons. Using sealants with an adhesive function would complement the high quality joints produced by RFSSW by not only protecting against corrosion but also contributing to the overall mechanical performance of the structure. To achieve the main goal of this project a work plan consisting of eight work packages has been devised. Two work packages are focused on the RFSSW process development using standard samples with and without adhesive sealant. In parallel the adhesive sealant technology, including surface pre-treatment will be developed. The hybrid joining solution developed in this project will be compared to conventional joining technologies to define its potential. Hybrid joining brings a number of advantages to production and performance of aircraft structures. The change from differential to integral design introduces new challenges in the analysis of mechanical performance. Hence, the damage tolerance behaviour of hybrid joints is also investigated in this project. Quality control methods will be investigated by selecting NDT methods and by process control based on online monitoring of parameters. In the last phase of this project technology demonstrators will be produced to evaluate the capabilities of the proposed technology in actual aircraft structures. The consortium (3 R&D and 2 industrial partners) has the exact fitting, prooven expertise and high excellence. HZG (coordinator) holds key patents.
[ "Products and Processes Engineering", "Materials Engineering" ]
W2916526362
PIXE analysis of stream water following the Mt. Hakone eruption on 30 June 2015 — temporal changes in elemental concentrations over two years
After the 2011 Off the Pacific Coast of Tohoku Earthquake on 11 March, 2011, volcanic activity in Japan was observed to increase. In this study, we use the PIXE method to analyze elemental concentrations in stream water flowing directly from the fumarolic area on Mount Hakone, which erupted on 30 June 2015. Throughout a two-year monitoring period following the eruption, concentrations of 12 dissolved elements were measured. We found that the stream water was strongly acidic. For one year after the eruption, the concentrations of magma-derived elements (S, Cl) and rock-derived elements (Al, Ca, Fe, K, Mg, Mn, and Na), except for Si, showed a clear decreasing trend. These measurements suggest that magmatic activity and fumarolic activity reduced gradually over one year. After this year-long period, elemental concentrations stopped decreasing and instead showed broadly flat levels with sporadic increases and decreases. However, throughout the year immediately following the eruption, the number of volcanic earthquakes was consistently at zero or close to zero. These different indications of volcanic activity suggest that the elemental concentrations in stream water may be more sensitive indicators of small changes in subterranean behavior than of the number of volcanic earthquakes.
[ "Earth System Science", "Physical and Analytical Chemical Sciences" ]
W2122898505
DEBT POLICY RULE, PRODUCTIVE GOVERNMENT SPENDING, AND MULTIPLE GROWTH PATHS: A NOTE
In a very interesting endogenous growth model, Futagami, Iwaisako, and Ohdoi [ Macroeconomic Dynamics 12 (2008), 445–462] study the long-run growth effect of borrowing for public investment. Their model exhibits (i) the multiplicity of balanced growth paths (BGPs) in the long run (two steady states) and (ii) a possible indeterminacy of the transition path to the high-growth BGP. The goal of this note is to show that their results depend on a sharp assumption, namely the definition of the public debt target as a ratio to private capital. If the target is defined in terms of public debt–to–GDP ratio, both results vanish: the model exhibits a unique BGP (no multiplicity) and the adjustment path to this unique equilibrium is determinate (no indeterminacy).
[ "Individuals, Markets and Organisations" ]
10.3389/fcimb.2016.00152
An in vitro co-culture mouse model demonstrates efficient vaccine-mediated control of Francisella tularensis SCHU S4 and identifies nitric oxide as a predictor of efficacy
Francisella tularensis is a highly virulent intracellular bacterium and cell-mediated immunity is critical for protection, but mechanisms of protection against highly virulent variants, such as the prototypic strain F. tularensis strain SCHU S4, are poorly understood. To this end, we established a co-culture system, based on splenocytes from naïve, or immunized mice and in vitro infected bone marrow-derived macrophages that allowed assessment of mechanisms controlling infection with F. tularensis. We utilized the system to understand why the clpB gene deletion mutant, ΔclpB, of SCHU S4 shows superior efficacy as a vaccine in the mouse model as compared to the existing human vaccine, the live vaccine strain (LVS). Compared to naïve splenocytes, ΔclpB-, or LVS-immune splenocytes conferred very significant control of a SCHU S4 infection and the ΔclpB-immune splenocytes were superior to the LVS-immune splenocytes. Cultures with the ΔclpB-immune splenocytes also contained higher levels of IFN-γ, IL-17, and GM-CSF and nitric oxide, and T cells expressing combinations of IFN-γ, TNF-α, and IL-17, than did cultures with LVS-immune splenocytes. There was strong inverse correlation between bacterial replication and levels of nitrite, an end product of nitric oxide, and essentially no control was observed when BMDM from iNOS-/- mice were infected. Collectively, the co-culture model identified a critical role of nitric oxide for protection against a highly virulent strain of F. tularensis.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1002/biot.201500255
Overcoming low yields of plant-made antibodies by a protein engineering approach
The commercial development of plant-based antibody production platforms is often limited by low and variable yields, but little is known about the factors that affect antibody accumulation during and after translation. Here, we present a strategy to identify yield-limiting regions in the transcript and protein. We exchanged variable heavy chain (VH) domain sequences between two human antibodies at structurally conserved positions, thus creating ten chimeric VH domains containing sequences from M12 (∼1000 μg/g leaf fresh weight [FW]) and 4E10 (∼100 μg/g FW). After transient expression in Nicotiana benthamiana leaves, we measured mRNA and protein levels by quantitative real-time PCR and surface plasmon resonance spectroscopy, respectively. Transcript levels were similar for all constructs, but antibody levels ranged from ∼250 μg/g to over 2000 μg/g FW. Analysis of the expression levels showed that: i) 4E10 yields were only marginally increased by suppression of post-transcriptional gene silencing; ii) the CDR3 of 4E10 contains a protease site; and iii) a bipartite, yield-limiting region exists in the CDR2/CDR3. Our findings highlight the strong impact of cotranslational and posttranslational events on antibody yields and show that protein engineering is a powerful tool that can be used to overcome the remaining limitations affecting antibody production in plants.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Biotechnology and Biosystems Engineering" ]
10.1016/j.cell.2013.05.014
XOTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin
The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate-assisted catalysis in which the proximal Ub activates the catalytic triad of the protease. Mutation of Ub Glu16 inhibits OTULIN activity by reducing k cat 240-fold. OTULIN overexpression or knockdown affects NF-κB responses to LUBAC, TNFα, and poly(I:C) and sensitizes cells to TNFα-induced cell death. We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1007/978-3-319-96553-6_4
Overview Of Geco A Project For Exploring And Integrating Signals From The Genome
Next Generation Sequencing is a 10-year old technology for reading the DNA, capable of producing massive amounts of genomic data - in turn, reshaping genomic computing. In particular, tertiary data analysis is concerned with the integration of heterogeneous regions of the genome; this is an emerging and increasingly important problem of genomic computing, because regions carry important signals and the creation of new biological or clinical knowledge requires the integration of these signals into meaningful messages. We specifically focus on how the GeCo project is contributing to tertiary data analysis, by overviewing the main results of the project so far and by describing its future scenarios.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1002/ijc.30445
A nonrandomized, prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy
To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch® system. Platinum-based AC was administered in 50 patients (27. 0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer-specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22. 2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0. 027). At a median follow-up of 31 months, the presence of CTC was associated with disease recurrence, cancer-specific and overall mortality (p-values < 0. 001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4. 9; p < 0. 001), cancer-specific (HR: 4. 2; p = 0. 003) and overall mortality (HR: 4. 2; p = 0. 001). The CTC status may be implemented in decision-making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
174031
Meet and learn what excellent science does for you and the society
Meet and learn What Excellent science does FOR YOU and the society is the major focus of the coordinated WeForYou action in performing the European Researchers’ Night 2014 and 2015 in Slovenia. Energy research & innovation, Environment & Climate Action, Health and ICT Research & Innovation are the priorities which will be tackled by a series of actions and opportunities for interchange of knowledge in the European Researchers’ Night 2014 and 2015 in Slovenia. The events in 2014 and 2015 in Slovenia will take place in: - Ljubljana, the main city square organized by Jožef Stefan Institute (JSI); - Novo mesto, organized by Faculty of Information Studies; - Piran and Piran bay, organized by National Institute of Biology; - Planica, Planetary Habitat Simulation Centre organised by JSI; - Krško, organized by Jožef Stefan Institute (JSI) The European Researchers' Night aims to bring researchers to the general public and to increase awareness of research and innovation activities, with a view to support the public recognition of researchers, creating an understanding of the impact of researchers' work on citizen's daily life, and encouraging young people to embark on scientific careers. Among the goals of WeForYou is one of special importance - presenting the researchers that have shown excellency in their results and achievement as ordinary people. Activities that are planned will enable the wide public audience to identify itself with the researchers’ life and to promote science in a firm expectation that the passed message to the young people will embark them on scientific careers. Children and adults addressed within the WeForYou activities will have the opportunity to understand science by experiencing its day-to-day practices, by frequenting the spaces and places where research is carried out and by coming into contact with its machinery and equipment, but above all by talking to those directly involved in scientific research that brings benefit to the society.
[ "Environmental Biology, Ecology and Evolution", "Products and Processes Engineering", "Prevention, Diagnosis and Treatment of Human Diseases", "The Social World and Its Interactions" ]
309848
Innate sensing of HIV and immune responses
Since its isolation in 1983 as a causative agent of AIDS, HIV-1 has remained an exceptional challenge. The human immune system usually ultimately fails at controlling infection by the virus. In contrast, most individuals infected with the related and poorly studied lentivirus HIV-2 do not develop AIDS. The immune response is clearly implicated in this protection, but the mechanisms are not well understood. DCs are a unique type of immune cell that sense pathogens and couple this sensing to the activation of innate and adaptive immunity. We have recently discovered that unlike HIV-1, HIV-2 is sensed in dendritic cells (DCs), a finding that is strikingly parallel to the in vivo situation. We found that sensing of the virus in DCs in vitro induces an antiviral innate response and activation of CD4+ and CD8+ T cells. Whether this adaptive response contributes to the lack of AIDS pathology in HIV-2 infected patients is unknown. Therefore, while the vast majorities of studies have focused on HIV-1, we believe that the HIV-2 represents a unique opportunity to discover how HIV-sensing in DCs translates into protective immune responses. To address this question, we propose an approach at the interface of immunology and virology. We propose to: 1) Unravel the type of CD4+ and CD8+ T cell responses induced by DCs that sense HIV-2. We will examine how naïve T cells respond to HIV-2 in vitro and how this compares with the response of memory T cells isolated from HIV-2 infected patients who control their virus. 2) Determine what is sensed by DCs in HIV-2. 3) Identify cellular regulators of HIV sensing in DCs. Altogether, this study will integrate molecular sensing of the virus and adaptive immunity to provide an understanding of how the immune response against HIV-2 operates. We believe that this may lead to novel approaches based on the manipulation of innate immunity against HIV-1 and HIV-2 infections and in other types of infection.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
219589
European frontiers: rural spaces and expanding states
Frontiers are dynamic zones of resistance and negotiation where local actors respond to the political/economic fluctuations of expanding states. Research on Europe’s frontier zones in the historic past has immediate relevance to the modern economic and political landscape, where the expansion of transnational markets is creating new dynamic frontier zones. Yet due to the typical top-down approach employed by archaeologists and historians, the local experience of living in a frontier has been largely overlooked. EUROFRONT adopts an innovative four-field methodology (archaeology, history, geomatics, and ethnography) to investigate two European frontiers in Crete and Dalmatia. Rich datasets will be developed for each region, synthesizing archaeological data, archival materials (e.g. tax registers and cadastral maps), paleoclimate data, and modern oral histories about villages in the regions. Advanced geospatial analyses will be used to detect patterns in population movement, settlement distribution, network connection, and agricultural production. During the project, the researcher will be trained in cutting-edge geomatics technologies, and the skills and knowledge she gains will enhance her reputation as a leading scholar of Early Modern archaeology and history in Europe. Results of the study will provide insight into how frontier communities are shaped by the process of state expansion from an economical, social, political, and environmental perspective. Project dissemination will prioritize publication of the raw data, training other scholars, and sparking an international dialogue about frontier zones that transects geographical and temporal boundaries. The project website and interactive online GIS will be critical deliverables that not only promote the study of frontiers but also give voice to the local experience through publication of maps, photographs, and interviews with local residents.
[ "The Study of the Human Past", "Human Mobility, Environment, and Space", "Computer Science and Informatics" ]
227457
Search for emergent phenomena in oxide nanostructures
Oxide nanostructures in low dimensions on well-defined metal surfaces form novel hybrid systems with tremendous potential and impact in fundamental research and for the emerging nanotechnologies. The focus of the project is on the fabrication of two-, quasi-one-, and quasi-zero-dimensional oxide nanostructure model systems suitable for elucidation of their emergent properties in terms of structure, electronics, magnetism, and catalytic chemistry. This will be achieved by controlled self-assembly in ultrahigh vacuum, with atomic-scale precision, and in-situ characterisation employing the full palette of modern surface science methodology. Established kinetic preparation routes as well as a new approach to steer the self-assembly via external fields will be applied to the growth of a variety of transition metal oxides on suitable substrate surface templates. The stabilisation mechanism of polar oxide surfaces in nanoscale oxide objects, the catalytic chemistry of a nanoscale inverse model catalyst consisting of oxide nanowires coupled to an array of one-dimensional metal step atoms, and the magnetic properties of a surface-supported oxide quantum dot superlattice will be among the emergent phenomena to be probed in this project. Such fundamental questions will be addressed in a close collaboration between state-of-the-art experimental and theoretical techniques. The possibility to separate dimensionality from nanoscale effects made possible by the model systems created here will add an extra dimension in the understanding of oxide nanophase systems.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1109/TBME.2013.2274816
Modeling And Analysis Of Individualized Pharmacokinetics And Pharmacodynamics For Volatile Anesthesia
The presented procedure aims to establish an in-depth understanding of a derived mathematical model for drug distribution, pharmacokinetics, and drug effect, pharmacodynamics, during volatile anesthesia. A physiologically based, patient-specific model is derived, where the pharmacokinetic (PK) part consists of multiple blood and tissue compartmental models, each adjusted to the weight, height, gender, and age of the patient. The pharmacodynamic (PD) part is described by an effect site compartment and the Hill equation both linking the hypnotic effect measured by the Bispectral Index (BIS) to the arterial anesthetic concentration. Via a global sensitivity analysis the patient-specific PK and PD variables and parameters are analyzed regarding their influence on the measurable outputs, which are the end-tidal concentration of the volatile anesthetic and the BIS. Via this analysis, the uncertainty introduced by PD variability is identified to be more significant than the uncertainty introduced by PK variability. A case study of isoflurane-based anesthesia shows that the simulation results of the individualized PK variables are in good accordance with the measured end-tidal concentration. However, the PD parameters need to be estimated online to predict the hypnotic depth, measured by the BIS, correctly. As a result of this study, the aim should be to focus on the individual identification of the PD parameters before and during anesthesia with future application in safe and robust model predictive control.
[ "Physiology in Health, Disease and Ageing", "Computer Science and Informatics", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1111/sifp.12055
The Stability Paradox: Why Expansion of Women's Education Has Not Delayed Early Union Formation or Childbearing in Latin America
Despite substantial improvements in women's education, the age at which Latin American women marry (cohabit) or become mothers for the first time has barely decreased over the past four decades. We refer to this as the “stability paradox. ” We examine the relationship between years of schooling and transitions to first union or child, analyzing retrospective information from 50 cohorts of women born between 1940 and 1989 in 12 Latin American countries. Absolute and relative measures of schooling are compared. Data is drawn from 38 Demographic Health Surveys (DHS) conducted between 1986 and 2012 in these countries. Results show that expected postponement in family transitions due to educational expansion was offset by a rise in union formation and childbearing within strata of absolute education, but stayed approximately constant within strata of relative education. The relative measure of education retains the stratifying power of education but neutralizes any effect attached to a specific number of years of schooling and the learning skills associated with them. This is consistent with the idea that access to education in Latin America reproduces existing patterns of socioeconomic advantage, rather than creating a more equitable distribution of learning opportunities and outcomes.
[ "The Social World and Its Interactions", "Human Mobility, Environment, and Space" ]
10.1073/pnas.1600503113
Bursts of activity in collective cell migration
Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems.
[ "Condensed Matter Physics", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1016/j.jamda.2017.09.026
The Prevalence and Correlates of Frailty in Urban and Rural Populations in Latin America, China, and India: A 10/66 Population-Based Survey
Background: There have been few cross-national studies of the prevalence of the frailty phenotype conducted among low or middle income countries. We aimed to study the variation in prevalence and correlates of frailty in rural and urban sites in Latin America, India, and China. Methods: Cross-sectional population-based catchment area surveys conducted in 8 urban and 4 rural catchment areas in 8 countries; Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico, China, and India. We assessed weight loss, exhaustion, slow walking speed, and low energy consumption, but not hand grip strength. Therefore, frailty phenotype was defined on 2 or more of 4 of the usual 5 criteria. Results: We surveyed 17,031 adults aged 65 years and over. Overall frailty prevalence was 15. 2% (95% confidence inteval 14. 6%–15. 7%). Prevalence was low in rural (5. 4%) and urban China (9. 1%) and varied between 12. 6% and 21. 5% in other sites. A similar pattern of variation was apparent after direct standardization for age and sex. Cross-site variation in prevalence of frailty indicators varied across the 4 indicators. Controlling for age, sex, and education, frailty was positively associated with older age, female sex, lower socioeconomic status, physical impairments, stroke, depression, dementia, disability and dependence, and high healthcare costs. Discussion: There was substantial variation in the prevalence of frailty and its indicators across sites in Latin America, India, and China. Culture and other contextual factors may impact significantly on the assessment of frailty using questionnaire and physical performance-based measures, and achieving cross-cultural measurement invariance remains a challenge. Conclusions: A consistent pattern of correlates was identified, suggesting that in all sites, the frailty screen could identify older adults with multiple physical, mental, and cognitive morbidities, disability and needs for care, compounded by socioeconomic disadvantage and catastrophic healthcare spending.
[ "Physiology in Health, Disease and Ageing", "Environmental Biology, Ecology and Evolution", "Human Mobility, Environment, and Space" ]
10.1016/j.cub.2014.10.042
Asymmetric processing of visual motion for simultaneous object and background responses
Visual object fixation and figure-ground discrimination in Drosophila are robust behaviors requiring sophisticated computation by the visual system, yet the neural substrates remain unknown. Recent experiments in walking flies revealed object fixation behavior mediated by circuitry independent from the motion-sensitive T4-T5 cells required for wide-field motion responses [1]. In tethered flight experiments under closed-loop conditions, we found similar results for one feedback gain, whereas intact T4-T5 cells were necessary for robust object fixation at a higher feedback gain and in figure-ground discrimination tasks. We implemented dynamical models (available at http://strawlab. org/asymmetric-motion/) based on neurons downstream of T4-T5 cells - one a simple phenomenological model and another, physiologically more realistic model - and found that both predict key features of stripe fixation and figure-ground discrimination and are consistent with a classical formulation [2]. Fundamental to both models is motion asymmetry in the responses of model neurons, whereby front-to-back motion elicits stronger responses than back-to-front motion. When a bilateral pair of such model neurons, based on well-understood horizontal system cells [3, 4], downstream of T4-T5 [5], is coupled to turning behavior, asymmetry leads to object fixation and figure-ground discrimination in the presence of noise. Furthermore, the models also predict fixation in front of a moving background, a behavior previously suggested to require an additional pathway [1]. Thus, the models predict several aspects of object responses on the basis of neurons that are also thought to serve a key role in background stabilization [6-12].
[ "Neuroscience and Disorders of the Nervous System", "Computer Science and Informatics" ]
10.1146/annurev-pharmtox-010814-124511
Synthetic lethal vulnerabilities of cancer
The great majority of targeted anticancer drugs inhibit mutated oncogenes that display increased activity. Yet many tumors do not contain such actionable aberrations, such as those harboring loss-of-function mutations. The notion of targeting synthetic lethal vulnerabilities in cancer cells has provided an alternative approach to exploiting more of the genetic and epigenetic changes acquired during tumorigenesis. Here, we review synthetic lethality as a therapeutic concept that exploits the inherent differences between normal cells and cancer cells. Furthermore, we provide an overview of the screening approaches that can be used to identify synthetic lethal interactions in human cells and present several recently identified interactions that may be pharmacologically exploited. Finally, we indicate some of the challenges of translating synthetic lethal interactions into the clinic and how these may be overcome.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W2019145052
Establishment of a cell line from the brain of grouper (Epinephelus akaara) for cytotoxicity testing and virus pathogenesis
Abstract We established and characterized a continuous cell line (EAGB) from the brain of grouper (Epinephelus akaara). EAGB cells multiplied well in MEM that was supplemented with 10% fetal bovine serum at 30 °C. The EAGB cell line consisted predominantly of fibroblast-like cells from grouper, which was confirmed by the sequence of mitochondrial 18s rRNA. Karyotyping indicated that the modal chromosome number was 60. The transfection efficiency of pEGFP-N3 into EAGB cells reached 34%. Bacterial cytotoxicity studies showed that the extracellular products from Vibrio alginolyticus or Vibrio anguillarum were toxic to EAGB cells. In addition, EAGB cells were susceptible to Singapore grouper iridovirus (SGIV) and viral nervous necrosis virus (VNNV), which was demonstrated by the presence of a severe cytopathic effect (CPE), abundant virus particles, and increased viral titers. Although the CPE was observed in soft-shelled turtle iridovirus (STIV)-infected EAGB cells, the virus titer was not increased and virus particles were not observed by electron microscopy. Nuclear morphological observations showed that STIV infection induced typical apoptotic bodies, whereas SGIV infection evoked non-apoptotic death in EAGB cells. The newly established EAGB cell line provided a useful tool for genetic manipulation, cytotoxicity testing, and virus pathogenesis.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Immunity, Infection and Immunotherapy" ]
10.1073/pnas.1705165114
Cancer cells induce interleukin-22 production from memory CD4+ T cells via interleukin-1 to promote tumor growth
IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4+ T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells. IL-1 receptor signaling via the transcription factors AhR and RORγt in T cells was necessary and sufficient for IL-22 production. In these settings, IL-1 induced IL-22 production from a mixed T helper cell population comprised of Th1, Th17, and Th22 cells, which was abrogated by the addition of anakinra. We confirmed these findings in vitro and in vivo in two murine tumor models, in primary human breast and lung cancer cells, and in deposited expression data. Relevant to ongoing clinical trials in breast cancer, we demonstrate here that the IL-1 receptor antagonist anakinra abrogates IL-22 production and reduces tumor growth in a murine breast cancer model. Thus, we describe here a previously unrecognized mechanism by which cancer cells induce IL-22 production from memory CD4+ T cells via activation of the NLRP3 inflammasome and the release of IL-1β to promote tumor growth. These findings may provide the basis for therapeutic interventions that affect IL-22 production by targeting IL-1 activity.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
986720
Adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning
The formation of a functional patterned (adaptation) vascular network is essential for development, tissue growth, and organ physiology. Several human vascular disorders arise from the mis-patterning (maladaptation) of blood vessels, such as arteriovenous malformations, aneurysms, and diabetic retinopathy. Blood flow is recognized as the main inducer for vascular patterning, yet very little is known about the molecular mechanisms that vascular patterning. C. Franco and others recently highlighted that endothelial cells polarize and migrate against the blood flow direction. Yet, how this behavior contributes to the overall process of vascular patterning is completely unknown. This project aims to study the dynamics of endothelial cells in vascular patterning during development, homeostasis, and disease. Taking advantage of a unique new transgenic mouse line reporting endothelial cell polarity in vivo, I will investigate endothelial cell behavior in vivo, including endothelial cell polarity, collective and individual migration and cell rearrangements, using 2-photon microscopy. I will extend this analysis to understand the involvement of endothelial flow-dependent polarity in formation and development of arteriovenous malformations. Finally, I will perform an in vivo functional screen to identify novel regulators of endothelial flow-dependent polarity, using a combination of automated image analysis and hemodynamics modelling. This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing" ]
896768
Protect traditional built heritage skills – pro-heritage
According to the climate change and energy policy of the EU, each member state needed to identify and develop a series of energy efficient goals and regulations, of which buildings are a key element, in order to reach the set goals. However, Europe has numerous historic buildings, which need permanent maintenance and refurbishment in order to fulfil the requirements of sustainability and use. When responsible bodies do spend money anyway, it seems logical and ecologically worthwhile to apply “soft” maintenance procedures, which save costs and also reduce energy consumption of historic buildings. Integrating these buildings into national climate change and energy policies seems therefore quite necessary and a challenge, as far as appropriate techniques and procedures are concerned, which can only be met through excellently trained craftsmen and apprentices of the crafts concerned. PRO-Heritage partners aim to offer initial and permanent education for professionals and craftsmen providing traditional competences and skills for built heritage, based on Best Practice of partner organisations. Additionally, PRO-Heritage is going to establish a structure and environment for regular journeyman's travel in Europe, in order to further support the exchange of competences and skills across Europe. Major needs addressed in PRO-Heritage are • to protect traditional competences and skills for built Cultural Heritage relevant for energy efficiency and renewable energy • the need to involve adequately educated and trained professionals and craftsmen in “soft” conservation, maintenance and ongoing care • the need to certify those professionals and craftsmen in order to give them recognition of their competences and skills Achieving better energy performance in historic buildings is a WIN-WIN situation for all – owners facing less energy costs, residents enjoying modern comfort at reasonable prices and society reducing energy consumption and CO2 emission.
[ "Earth System Science", "Products and Processes Engineering" ]
10.1002/lpor.201700226
Stretchable Photonic ‘Fermi Arcs’ in Twisted Magnetized Plasma
Weyl points, three-dimensional linear bulk bands crossings possessing intrinsic helicities, are counterparts of magnetic monopoles in the momentum space. One of the most important features of Weyl semimetals is the presence of topologically protected non-trivial surface states at the boundary that connect between Weyl points of opposite charges. In condensed matter physics, these surface states are called Fermi arcs whose length measures the topological strength of the system. Here we theoretically show that photonic ‘Fermi arcs’ can exist at the interface between two magnetized plasma under static bias magnetic fields of different orientations, i. e. a twisted configuration, whereas the length of the ‘Fermi arcs’ can be arbitrarily stretched by varying the relative orientation and intensities of two static bias magnetic fields. Interestingly, the ‘Fermi arcs’ join two Weyl points of the same sign but residing on different side of the interface. Our work gives insight to the connectivity of ‘Fermi arcs’ between two topological semimetals and could open gateway towards tunable photonic topological systems.
[ "Fundamental Constituents of Matter", "Condensed Matter Physics" ]
W2800346076
Time Headway analysis on urban roads of the city of Marrakesh
Abstract Vehicular Time Headway or Inter-arrival time is an important parameter in traffic flow theory. It has a major effect on traffic simulation especially in the traffic generation process. Most of the previous research on Time Headway modeling have focused on homogeneous traffic, on uninterrupted urban roads, freeways or highways. The situation in Marrakesh is very different where traffic is heterogeneous and intersections are close especially signalized ones in the center of the city. This paper proposes a study of Time Headway on four urban roads with heterogeneous traffic conditions, interrupted by a signalized intersection. A sampling approach is used taking into consideration the signal plan of the preceding intersection. Time Headway samples are then compared to theoretical models used in literature adding also a Paretian model (Pareto type IV) which was discussed in the past as a potential candidate. The study shows that TH distribution in these roads is different from the usually studied roads which is why some of the common models are rejected compared to Pareto type IV that fits well all the TH samples representing different traffic flow levels.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
10.1088/0953-4075/43/21/213001
High Order Harmonic And Attosecond Pulse Generation On Plasma Mirrors Basic Mechanisms
When an intense femtosecond laser pulse hits an optically polished surface, it generates a dense plasma that itself acts as a mirror, known as the plasma mirror. As this mirror reflects the high-intensity laser field, its nonlinear temporal response can lead to a periodic temporal distortion of the reflected wave, associated with a train of attosecond light pulses, and, in the frequency domain, to the generation of high-order harmonics of the laser. This tutorial presents detailed theoretical and numerical analysis of the two dominant harmonic generation mechanisms identified so far, coherent wake emission and the relativistic oscillating mirror. Parametric studies of the emission efficiency are presented for these two regimes, and the phase properties of the corresponding harmonics are discussed. This theoretical study is complemented by a synthesis of recent experimental results, which establishes that these two mechanisms indeed dominate harmonic generation on plasma mirrors.
[ "Fundamental Constituents of Matter", "Physical and Analytical Chemical Sciences" ]
10.1038/s41590-018-0110-6
Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies /631/1647/2017 /631/1647/2017/2079 technical-report
Transcriptome profiling is widely used to infer functional states of specific cell types, as well as their responses to stimuli, to define contributions to physiology and pathophysiology. Focusing on microglia, the brain's macrophages, we report here a side-by-side comparison of classical cell-sorting-based transcriptome sequencing and the 'RiboTag' method, which avoids cell retrieval from tissue context and yields translatome sequencing information. Conventional whole-cell microglial transcriptomes were found to be significantly tainted by artifacts introduced by tissue dissociation, cargo contamination and transcripts sequestered from ribosomes. Conversely, our data highlight the added value of RiboTag profiling for assessing the lineage accuracy of Cre recombinase expression in transgenic mice. Collectively, this study indicates method-based biases, reveals observer effects and establishes RiboTag-based translatome profiling as a valuable complement to standard sorting-based profiling strategies.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Neuroscience and Disorders of the Nervous System" ]
W4281842343
O PAPEL DO FARMACÊUTICO NA PANDEMIA DE COVID-19
Em dezembro de 2019, na China, foram identificados casos de uma nova síndrome respiratória aguda, provocada por um novo coronavírus (2019-nCoV), que foi denominada COVID-19 (Coronavirus disease 2019). Devido ao agravamento rápido da doença, a situação foi dada como crítica, e os profissionais da saúde da linha de frente ficaram diretamente envolvidos no cuidado, diagnóstico e tratamento dos pacientes com COVID-19. Nessas circunstâncias, o farmacêutico exerce um papel importante, pois deve agir no controle da transmissão da doença e na atenção às necessidades da comunidade, disseminando informações, além de assumir a responsabilidade da implementação de estratégias para promoção do uso racional de medicamentos, em virtude das consequências danosas do seu uso inadequado.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "The Social World and Its Interactions" ]
10.1039/c8ee03423k
Powering sustainable development within planetary boundaries
Designing energy systems within planetary boundaries is crucial to preserving the Earth's ecological capacity given the power sector's environmental footprint.
[ "Earth System Science", "Products and Processes Engineering" ]
216393
Remote-Activated delivery of therapeutic exosomes (radote) via an injectable peg hydrogel carrier
As a Marie Skłodowska-Curie Fellow, I will develop and demonstrate remote-activated delivery of biological therapeutics loaded into an injectable hydrogel, where delivery is triggered by applying near-infrared (NIR) light that safely and non-invasively penetrates deep into living tissues. The hydrogel carrier will be designed to deliver and stabilize cell-derived exosomes and microvesicles, together referred to as extracellular vesicles (EVs), which have recently gained attention for their ability to effectively deliver biological information and cargo directly to target cells. Developing sophisticated delivery systems for EVs will streamline their translation to clinical application, enabling the huge potential for this novel biological therapeutic to be fully realized. This system will be advantageous in simultaneously providing localized delivery, enhanced EV stability, and crucially, externally triggered release. This project will provide the first demonstration of localized and controlled delivery of EVs, with the added novelty of an externally NIR-triggered delivery system. By combining my expertise in designer hydrogel chemistry, the supervision of Prof. Molly Stevens at Imperial College London (ICL) who runs a world-class interdisciplinary biomaterials-focused group, and a secondment with The Technology Partnership (TTP) specializing in technology translation, this project is ideally situated to deliver the highest quality results.
[ "Materials Engineering", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases", "Synthetic Chemistry and Materials", "Cell Biology, Development, Stem Cells and Regeneration" ]
757247
Global data justice in the era of big data: toward an inclusive framing of informational rights and freedoms
The increasing adoption of digital technologies worldwide creates data flows from places and populations that were previously digitally invisible. The resulting ‘data revolution’ is hailed as a transformative tool for human and economic development. Yet the revolution is primarily a technical one: the power to monitor, sort and intervene is not yet connected to a social justice agenda, nor have the organisations involved addressed the discriminatory potential of data technologies. Instead, the assumption is that the power to visualise and monitor will inevitably benefit the poor and marginalised. This research proposes that a conceptualisation of data justice is necessary to determine ethical paths through a datafying world. Its two main aims are: first, to provide the first critical assessment of the case for, and the obstacles to, data justice as an overall framework for data technologies’ design and governance. Second, to present a conceptual framework for data justice, refining it through public debate. The project will develop an interdisciplinary approach integrating critical data studies with development studies and legal philosophy. Using Sen's Capabilities Approach, it will conceptualise data justice along three dimensions of freedoms: (in)visibility, digital (dis)engagement, and nondiscrimination. Multi-sited ethnography in combination with digital methods will be used to build a conceptual framework, which will then be tested and shaped by debates held in nine locations worldwide. The research is groundbreaking in terms of 1) its use of the Capabilities Approach to address the social impacts of data technologies; 2) its integrative approach to problems previously addressed by the fields of law, informatics and development studies, and 3) its aim to reconcile negative with positive technologically-enabled freedoms, integrating data privacy, nondiscrimination and non-use of data technologies into the same framework as representation and access to data.
[ "The Social World and Its Interactions", "Institutions, Governance and Legal Systems", "Computer Science and Informatics" ]
10.1093/gbe/evs054
The population genomics of a fast evolver: High levels of diversity, functional constraint, andmolecular adaptation in the tunicate Ciona intestinalis
Phylogenomics has revealed the existence of fast-evolving animal phyla in which the amino acid substitution rate, averaged across many proteins, is consistently higher than in other lineages. The reasons for such differences in proteome-wide evolutionary rates are still unknown, largely because only a handful of species offer within-species genomic data from which molecular evolutionary processes can be deduced. In this study, we use next-generation sequencing technologies and individual whole-transcriptome sequencing to gather extensive polymorphism sequence data sets from Ciona intestinalis. Ciona is probably the best-characterized member of the fast-evolving Urochordata group (tunicates), which was recently identified as the sister group of the slow-evolving vertebrates. We introduce and validate a maximum-likelihood framework for single-nucleotide polymorphism and genotype calling, based on high-throughput short-read typing. We report that the C. intestinalis proteome is characterized by a high level of within-species diversity, efficient purifying selection, and a substantial percentage of adaptive amino acid substitutions. Weconclude that the increased rate of amino acid sequence evolution in tunicates,when comparedwith vertebrates, is the consequence of both a 2-6 times higher per-year mutation rate and prevalent adaptive evolution.
[ "Integrative Biology: from Genes and Genomes to Systems", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1103/PhysRevX.7.021037
Physical model of the genotype-to-phenotype map of proteins
How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to function. We therefore treat protein as learning amorphous matter that evolves towards such a mechanical function: Genes are binary sequences that encode the connectivity of the amino acid network that makes a protein. The gene is evolved until the network forms a shear band across the protein, which allows for long-range, soft modes required for protein function. The evolution reduces the high-dimensional sequence space to a low-dimensional space of mechanical modes, in accord with the observed dimensional reduction between genotype and phenotype of proteins. Spectral analysis of the space of 106 solutions shows a strong correspondence between localization around the shear band of both mechanical modes and the sequence structure. Specifically, our model shows how mutations are correlated among amino acids whose interactions determine the functional mode.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Condensed Matter Physics", "Integrative Biology: from Genes and Genomes to Systems" ]
W2299480983
Spillway discharges by modification of weir shapes and overflow surroundings
Almost all spillways of mid-size dams in Korea are overflow weir. To investigate the flood control capacity of overflow spillway, 3D numerical simulations were analyzed the discharge of a dam spillway for different weir shapes. Hydraulic model experiments, downsized as scale factor of 40 to 1 by Froude similitude were also carried out to verify the numerical results. Overflow phases and discharges of the linear labyrinth weir and the curved labyrinth weir were compared with those of the linear ogee weir. It was found that the discharge of the labyrinth weir was 71 % greater than that of the linear ogee weir at low reservoir elevation because the labyrinth weir had a longer effective length. However, as the elevation of the water surface rose, the discharge slope of the labyrinth weir became milder by submergence and nappe interference in the side channel. Structural modification of the overflow surroundings such as changing the approaching channel elevation, lowering the bed elevation of the side channel, and moving the weir structure toward the reservoir were also considered to examine the discharge capacity of the spillway. Lowering the bed elevation of the side channel was found to be the most effective option.
[ "Products and Processes Engineering", "Earth System Science" ]
interreg_2707
Polycentric Planning Models for Local Development in Territories interested by Corridor 5 and its TEN-T ramifications
The main problem addressed is the marginalization that a major transport infrastructure (MTI) can cause to alpine areas. The project aims at making mountain areas catch the opportunities of MTIs, rather than just suffer their environmental and social impact, targeting the phases of piloting and policy implementation. The project foresees the elaboration of an unbiased method to measure the value of an alpine area and to maximize it, given the presence of a MTI. A polycentric development toolkit will synthesize the method providing indication to public actors for each phase of MTIs life-cycle. Pilot actions will test some solutions and final validation of the toolkit will lead to guidelines integrating project results in transnational policies, adopted by policy makers at different administrative level. A transversal activity will be the involvement of local communities to build consensus, raising awareness on the importance of participating and controlling public choices/processes.
[ "Human Mobility, Environment, and Space", "Institutions, Governance and Legal Systems", "Earth System Science" ]
10.1016/j.semcdb.2015.08.013
Pax4 acts as a key player in pancreas development and plasticity
The embryonic development of the pancreas is orchestrated by a complex and coordinated transcription factor network. Neurogenin3 (Neurog3) initiates the endocrine program by activating the expression of additional transcription factors driving survival, proliferation, maturation and lineage allocation of endocrine precursors. Among the direct targets of Neurog3, Pax4 appears as one of the key regulators of β-cell specification. Indeed, mice lacking Pax4 die a few days postpartum, as they develop severe hyperglycemia due to the absence of mature pancreatic β-cells. Pax4 also directly regulates the expression of Arx, a gene that plays a crucial role in α-cell specification. Comparative analysis of Pax4 and Arx mutants, as well as Arx/Pax4 double mutants, showed that islet subtype destiny is mainly directed by cross-repression of the Pax4 and Arx factors. Importantly, the ectopic expression of Pax4 in α-cells was found sufficient to induce their neogenesis and conversion into β-like cells, not only during development but also in adult rodents. Therefore, differentiated endocrine α-cells can be considered as a putative source for insulin-producing β-like cells. These findings have clearly widened our understanding regarding pancreatic development, but they also open new research avenues in the context of diabetes research.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1007/JHEP04(2015)172
Excessive Higgs Pair Production With Little Met From Squarks And Gluinos In The Nmssm
In the presence of a light singlino-like LSP in the NMSSM, the missing transverse energy - MET - signature of squark/gluino production can be considerably reduced. Instead, a pair of Higgs bosons is produced in each event. We propose benchmark points for such scenarios, which differ in the squark and gluino masses, and in their decay cascades. Events for these points are simulated for the run II of the LHC at 13 TeV centre of mass energy. After cuts on the transverse momenta of at least four jets, and requiring two tau-leptons from one Higgs decay, we find that the invariant mass of two b-jets from the other Higgs decay shows clear peaks above the background. Despite the reduced MET, this search strategy allows to see signals for sufficiently large integrated luminosities, depending on the squark/gluino masses.
[ "Fundamental Constituents of Matter", "Computer Science and Informatics" ]
interreg_3771
The empress's route - Cultural and flavour itineraries between Veneto, Friuli and Slovenia
This initiative is going to carry out integrated actions to promote and enhance the cultural and historical traditions, and the typical productions of the whole Programme-area, in order to foster the development of tourism and of the other economic resources in the territory. The project aims at drawing an ideal line, in keeping with the tradition of the ancient courts of Europe, and especially of the Serenissima Republic and the Hapsburg imperial court, in a historical context going from the 18th to the 20th century, and characterized by dramatic economic and social changes. The territory under examination, located between Veneto, Friuli Venezia Giulia and Slovenia, is endowed with a very rich historical, naturalistic and architectural heritage. In this regard, the project is going to foster the enhancement of these resources as well as of other economic resources, to increase tourism through a concerted system of communication and promotion, whose core has been detected in the “Empress’s route”. For a virtual tour, please browse through the above-mentioned web site. The cultural relevance of this initiative makes it possible to support the rural development of the partner areas. Wine is a niche product and is therefore the best expression of culture, tradition and history of the whole territory. Centred on the world of wine production, some tourist packages will be devised and will be within their full rights to enter the national and international tourist circuits.
[ "Human Mobility, Environment, and Space", "Studies of Cultures and Arts" ]
171093
Sperone speroni (1500-1588) and the rebirth of sophistry in the italian renaissance
This two-year research project aims to analyze the works of Sperone Speroni degli Alvarotti (Padua 1500–1588), his re-evaluation of ancient sophistic perspectives and his legacy in the early modern age. Speroni was one of the most important protagonists of the Renaissance debate on language and logic as well as civil and speculative philosophy. Educated as an Aristotelian, he eventually developed a distinctive philosophy and was the first to challenge Plato’s (327-447 BCE) condemnation of sophists. Despite the fact that Speroni was a central figure of Renaissance philosophy and literature in the vernacular, he is one of the most neglected authors in scholarly production. Furthermore, scholars have considered Speroni’s interest in ancient sophists as a marginal aspect of his philosophy and have disregarded the paramount role of the period’s vernacular writing on sophistry that began with his works and spread throughout sixteenth-century Italy. This project will not only contribute to the research on vernacular Aristotelianism funded by an ERC Starting Grant 2013 (ARISTOTLE – 335949) and led by Marco Sgarbi but also fill the gap in international studies with a complete analysis of the subject. Teodoro Katinis, an Experienced Researcher educated in European institutions and at Johns Hopkins University (U.S.A.), presents a research proposal from which the ground-breaking findings will revolutionize the traditional scholarly approach to a crucial period of the history of Western culture. Katinis expects that the development of this project will profoundly impact his career. Thanks to the training provided by Ca’ Foscari University in Venice and to its international network, Katinis will acquire new skills and build fruitful relations with European institutions and scholars. The training, network and publication of the project’s outcomes will increase Katinis’ possibilities of obtaining an eventual ERC Grant.
[ "Texts and Concepts", "The Study of the Human Past" ]
Q2054065
SMART CHIAENZA
O OBJETIVO DA COMUNICAÇÃO É FACILITAR INVESTIMENTOS DESTINADOS A APOIAR A AQUISIÇÃO DE COMPETÊNCIAS POR EMPRESAS QUE PERMITAM O LANÇAMENTO E CONSOLIDAÇÃO DE UMA TRAJETÓRIA DE INOVAÇÃO, ATRAVÉS DE PROJETOS DE INVESTIMENTO EM PRODUTOS/SERVIÇOS, PROCESSOS, INOVAÇÃO ORGANIZACIONAL E COMERCIAL, TAMBÉM A SEREM IMPLEMENTADOS ATRAVÉS DE PROJETOS DE REDE, FINANCIAMENTO DOS CUSTOS DE PATENTES DE IDEIAS INOVADORAS, CUSTOS LIGADOS À PROTOTIPAGEM, CUSTOS RELACIONADOS COM O DESENVOLVIMENTO DE COMPETÊNCIAS DIGITAIS.
[ "Products and Processes Engineering", "Individuals, Markets and Organisations" ]
W2005743391
Silicon-based long-wavelength III&#x2013;V quantum-dot lasers
The realization of electrically-pumped lasers on a Si platform will permit the creation of complex optoelectronic circuits, which will enable chip-to-chip and system-to-system optical communication. Direct epitaxial growth of III–V semiconductor materials on Si or Ge substrates is the most promising approach for producing lasers on Si. III–V compound quantum dots - semiconductor nanosized crystals - are very attractive for producing III–V/Si laser diodes with the advantages of lower threshold current density and less sensitivity to defects relative to conventional quantum wells. Here we present studies on the development of InAs/GaAs quantum-dot lasers monolithically grown on Si, Ge, and Ge-on-Si substrates. Room-temperature lasing near the telecommunications wavelength of 1300 nm have been demonstrated at room temperature with low threshold current densities for InAs/GaAs quantum-dot lasers grown on both Si, and Ge substrates.
[ "Condensed Matter Physics", "Synthetic Chemistry and Materials", "Systems and Communication Engineering", "Materials Engineering" ]
10.1111/1567-1364.12196
The Yeast Oligopeptide Transporter Opt2 Is Localized To Peroxisomes And Affects Glutathione Redox Homeostasis
Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is synthesized de novo solely in the cytosol and must subsequently be transported to other cellular compartments. The mechanisms of glutathione transport into and out of organelles remain largely unclear. We show that budding yeast Opt2, a close homolog of the plasma membrane glutathione transporter Opt1, localizes to peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox homeostasis. Furthermore, ∆opt2 strains display synthetic lethality with deletions of genes central to iron homeostasis that require mitochondrial glutathione redox homeostasis. Our results shed new light on the importance of peroxisomes in cellular glutathione homeostasis.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1007/s10071-011-0391-8
Spatial cognition in zebrafish: The role of strain and rearing environment
Two strains of zebrafish, WIK and a second-generation wild strain were reared in either a structurally simple or complex environment and compared in their ability to locate a food reward in a five-chambered maze. There was a significant interaction within subjects between rearing environment and trial, indicating that the consistency of learning varied depending on rearing environment, with those reared in a structurally simple environment showing a slower rate of learning. Fish of both strains reared in a structurally complex environment were smaller than those reared in a simple environment. Our study demonstrates, for the first time in zebrafish, that performance in a learning task as an adult is sensitive to rearing conditions during development.
[ "Neuroscience and Disorders of the Nervous System", "Environmental Biology, Ecology and Evolution" ]
10.1007/s00018-018-2789-9
Challenges and approaches to understand cholesterol-binding impact on membrane protein function: an NMR view
Experimental evidence for a direct role of lipids in determining the structure, dynamics, and function of membrane proteins leads to the term ‘functional lipids’. In particular, the sterol molecule cholesterol modulates the activity of many membrane proteins. The precise nature of cholesterol-binding sites and the consequences of modulation of local membrane micro-viscosity by cholesterol, however, is often unknown. Here, we review the current knowledge of the interaction of cholesterol with transmembrane proteins, with a special focus on structural aspects of the interaction derived from nuclear magnetic resonance approaches. We highlight examples of the importance of cholesterol modulation of membrane protein function, discuss the specificity of cholesterol binding, and review the proposed binding motifs from a molecular perspective. We conclude with a short perspective on what could be future trends in research efforts targeted towards a better understanding of cholesterol/membrane protein interactions.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W1987473619
Formation of black carbon-like and alicyclic aliphatic compounds by hydroxyl radical initiated degradation of lignin
Abstract Exposure of lignin-derived organic matter (OM) to hydroxyl radicals originating from Fenton type reactions generates condensed aromatic and alicyclic aliphatic compounds, as shown using ultrahigh resolution mass spectrometry. Although condensed aromatic compounds are common in soil and dissolved OM, their presence has been attributed largely to combustion. A non-pyrogenic route for the formation of condensed aromatic compounds from lignin is suggested here, specifically that hydroxyl radical-initiated oxidation of lignin is capable of producing black carbon-like condensed aromatic compounds. Alicyclic aliphatic compounds are also produced, likely as part of a concerted process involving ring opening, polymerization and/or cyclization and hydrogen abstraction. Hydroxyl radicals associated with lignin degradation are produced through photochemistry in aqueous systems and enzymatic microbial processes in soil.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
10.3791/52770
Hybrid Μct Fmt Imaging And Image Analysis
Fluorescence-mediated tomography (FMT) enables longitudinal and quantitative determination of the fluorescence distribution in vivo and can be used to assess the biodistribution of novel probes and to assess disease progression using established molecular probes or reporter genes. The combination with an anatomical modality, e. g. , micro computed tomography (µCT), is beneficial for image analysis and for fluorescence reconstruction. We describe a protocol for multimodal µCT-FMT imaging including the image processing steps necessary to extract quantitative measurements. After preparing the mice and performing the imaging, the multimodal data sets are registered. Subsequently, an improved fluorescence reconstruction is performed, which takes into account the shape of the mouse. For quantitative analysis, organ segmentations are generated based on the anatomical data using our interactive segmentation tool. Finally, the biodistribution curves are generated using a batch-processing feature. We show the applicability of the method by assessing the biodistribution of a well-known probe that binds to bones and joints.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physical and Analytical Chemical Sciences", "Computer Science and Informatics" ]
W2013331954
Instantaneous model adaptation method for reverberant speech recognition
An acoustic model adaptation algorithm is proposed for reverberant speech recognition. Inspired by the eigenvoice adaptation framework, multiple acoustic models reflecting various reverberant environments are combined for instantaneous adaptation. Using artificially generated reverberant speech, multiple acoustic models are trained according to multiple reverberation times. The mean vectors of the optimal acoustic model are obtained as a weighted sum of those of multiple acoustic models by using a maximum-likelihood criterion. For effective model combination, reverberant speech is preprocessed. Experiments on English continuous speech recognition tasks in a simulated reverberant environment show that the proposed method performs better than the conventional adaptation techniques.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1109/JPHOT.2015.2446203
Multiuser Miso Transceiver Design For Indoor Downlink Visible Light Communication Under Per Led Optical Power Constraints
Light-emitting diode (LED)-based visible light communication (VLC), combining illumination and communication, is a promising technique for providing high-speed, low-cost indoor wireless services. In indoor environments, multiple LEDs routinely used as lighting sources may also be concomitantly invoked to support wireless services for multiple users, thus forming a multiuser multiple-input–single-output (MU-MISO) system. Since the user terminals detect all the light rays impinging from multiple LEDs, inter-user interference may severely degrade the attainable system performance. Hence, we conceive a transceiver design for indoor VLC MU-MISO systems to suppress the multiuser interference (MUI). In contrast to classic radio-frequency (RF) communication, in VLC, the signals transmitted from the LEDs are restricted by optical constraints, such as the real-valued nonnegativity of the optical signal, the maximum permissible optical intensity, and the constant brightness requirements of the LEDs. Given these practical constraints, we design the optimal transceiver relying on the objective function of minimizing the maximum mean square error (MMSE) between the legitimate transmitted and received signals of the users and show that it can be readily found by solving a convex second-order cone program. Then, we also propose a simplified transceiver design by incorporating zero-forcing (ZF) transmit precoding (TPC) and show that the TPC coefficients can be efficiently found by solving a linear program. The performance of both the optimal and the simplified transceiver is characterized by comprehensive numerical results under diverse practical VLC system setups.
[ "Systems and Communication Engineering", "Physical and Analytical Chemical Sciences" ]
10.1103/PhysRevB.98.085302
Coupled wire model of Z4 orbifold quantum Hall states
We introduce a coupled wire model for a sequence of non-Abelian quantum Hall states that generalize the Z4 parafermion Read-Rezayi state. The Z4 orbifold quantum Hall states occur at filling factors ν=2/(2m-p) for odd integers m and p, and have a topological order with a neutral sector characterized by the orbifold conformal field theory with central charge c=1 at radius R=p/2. When p=1 the state is Abelian. The state with p=3 is the Z4 Read-Rezayi state, and the series of p≥3 defines a sequence of non-Abelian states that resembles the Laughlin sequence. Our model is based on clustering of electrons in groups of four, and is formulated as a two fluid model in which each wire exhibits two phases: a weak clustered phase, where charge e electrons coexist with charge 4e bosons and a strong clustered phase where the electrons are strongly bound in groups of four. The transition between these two phases on a wire is mapped to the critical point of the four-state clock model, which in turn is described by the orbifold conformal field theory. For an array of wires coupled in the presence of a perpendicular magnetic field, strongly clustered wires form a charge 4e bosonic Laughlin state with a chiral charge mode at the edge, but no neutral mode and a gap for single electrons. Coupled wires near the critical state form quantum Hall states with a gapless neutral mode described by the orbifold theory. The coupled wire approach allows us to employ the Abelian bosonization technique to fully analyze the physics of single wire, and then to extract most topological properties of the resulting non-Abelian quantum Hall states. These include the list of quasiparticles, their fusion rules, the correspondence between bulk quasiparticles and edge topological sectors, and most of the phases associated with quasiparticles winding one another.
[ "Condensed Matter Physics", "Mathematics" ]
W2979982423
VDJbase: an adaptive immune receptor genotype and haplotype database
Abstract VDJbase is a publicly available database that offers easy searching of data describing the complete sets of gene sequences (genotypes and haplotypes) inferred from adaptive immune receptor repertoire sequencing datasets. VDJbase is designed to act as a resource that will allow the scientific community to explore the genetic variability of the immunoglobulin (Ig) and T cell receptor (TR) gene loci. It can also assist in the investigation of Ig- and TR-related genetic predispositions to diseases. Our database includes web-based query and online tools to assist in visualization and analysis of the genotype and haplotype data. It enables users to detect those alleles and genes that are significantly over-represented in a particular population, in terms of genotype, haplotype and gene expression. The database website can be freely accessed at https://www.vdjbase.org/, and no login is required. The data and code use creative common licenses and are freely downloadable from https://bitbucket.org/account/user/yaarilab/projects/GPHP.
[ "Immunity, Infection and Immunotherapy", "Integrative Biology: from Genes and Genomes to Systems", "Computer Science and Informatics" ]
10.1161/JAHA.115.002681
Diastolic Left Ventricular Function In Relation To Circulating Metabolic Biomarkers In A General Population
Background The metabolic signature associated with subclinical diastolic left ventricular (LV) dysfunction in the population remains ill defined. Methods and Results In 711 randomly recruited Flemish (50. 8% women; mean age, 50. 8 years), we assessed echocardiographic Doppler indexes of diastolic LV function in relation to 44 circulating metabolites determined by nuclear magnetic resonance spectroscopy. In multivariable‐adjusted regression analysis with Bonferroni correction of significance levels applied, peak a’ decreased ( P ≤0. 048) and e’/a’ increased ( P ≤0. 044) with circulating tyrosine, high‐density lipoprotein apolipoproteins, glucose+glutamine, and an unidentified molecule. Effect sizes expressed per 1‐SD increment in the metabolite ranged from −0. 277 to −0. 203 cm/s for peak a’ and from +0. 047 to +0. 054 for e’/a’. In addition, peak a’ decreased ( P ≤0. 031) with glucose+2‐aminobutyrate (−0. 261 cm/s) and glucose+2‐phosphoglycerate (−0. 209 cm/s). In partial least square discriminant analysis (PLS‐DA), metabolites associated with normal diastolic LV function (n=538) included glucose+glutamine, glucose+2‐aminobutyrate, and glucose+2‐phosphoglycerate, whereas those siding with abnormal function encompassed 4‐aminobutyrate, 4‐hydroxybutyrate, creatinine, and phosphocholine. In receiver operating characteristics plots, adding 3 latent factors identified by PLS‐DA to prohormone brain natriuretic peptide increased ( P <0. 0001) the area under the curve from 0. 64 (95% CI, 0. 58–0. 68) to 0. 73 (0. 68–0. 78). Conclusions In a general population, circulating metabolites indicative of energy substrate utilization and protection against oxidative stress differentiated normal from abnormal diastolic LV function. These findings improve our understanding of the pathophysiology underlying deterioration of diastolic LV function and potentially point to new targets for prevention and treatment of this condition.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
2726329
Developing and implementing sustainability-based solutions for bio-based plastic production and use to preserve land and sea environmental quality in europe
The project BIO-PLASTICS EUROPE addresses the topic „Sustainable solutions for bio-based plastics on land and sea“ (Topic identifier: CE-BG-06-2019), within the focus area „Connecting economic and environmental gains - the Circular Econonmy (CE)“ and will focus on sustainability strategies and solutions for bio-based products to support the Plastics Strategy. This shall include innovative product design and business models facilitating efficient reuse and recycling strategies and solutions, including ensuring the safety of recycled materials when used for toys or packaging food stuffs. In line with the EU strategy on international cooperation in research and innovation and in order to encourage the further replication, the European consortium is complemented by a partner in Malaysia, providing an added value and helping them to address the many problems they face.
[ "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution", "Biotechnology and Biosystems Engineering" ]
W2084716952
Bayesian Disease Classification Using Copy Number Data
DNA copy number variations (CNVs) have been shown to be associated with cancer development and progression. The detection of these CNVs has the potential to impact the basic knowledge and treatment of many types of cancers, and can play a role in the discovery and development of molecular-based personalized cancer therapies. One of the most common types of high-resolution chromosomal microarrays is array-based comparative genomic hybridization (aCGH) methods that assay DNA CNVs across the whole genomic landscape in a single experiment. In this article we propose methods to use aCGH profiles to predict disease states. We employ a Bayesian classification model and treat disease states as outcome, and aCGH profiles as covariates in order to identify significant regions of the genome associated with disease subclasses. We propose a principled two-stage method where we first make inferences on the underlying copy number states associated with the aCGH emissions based on hidden Markov model (HMM) formulations to account for serial dependencies in neighboring probes. Subsequently, we infer associations with disease outcomes, conditional on the copy number states, using Bayesian linear variable selection procedures. The selected probes and their effects are parameters that are useful for predicting the disease categories of any additional individuals on the basis of their aCGH profiles. Using simulated datasets, we investigate the method's accuracy in detecting disease category. Our methodology is motivated by and applied to a breast cancer dataset consisting of aCGH profiles assayed on patients from multiple disease subtypes.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1111/1746-8361.12043
Accuracy And Evidence
In "A Nonpragmatic Vindication of Probabilism", Jim Joyce argues that our credences should obey the axioms of the probability calculus by showing that, if they don't, there will be alternative credences that are guaranteed to be more accurate than ours. But it seems that accuracy is not the only goal of credences: there is also the goal of matching one's credences to one's evidence. I will consider four ways in which we might make this latter goal precise: on the first, the norms to which this goal gives rise act as 'side constraints' on our choice of credences; on the second, matching credences to evidence is a goal that is weighed against accuracy to give the overall cognitive value of credences; on the third, as on the second, proximity to the evidential goal and proximity to the goal of accuracy are both sources of value, but this time they are incomparable; on the fourth, the evidential goal is not an independent goal at all, but rather a byproduct of the goal of accuracy. All but the fourth way of making the evidential goal precise are pluralist about credal virtue: there is the virtue of being accurate and there is the virtue of matching the evidence and neither reduces to the other. The fourth way is monist about credal virtue: there is just the virtue of being accurate. The pluralist positions lead to problems for Joyce's argument; the monist position avoids them. I endorse the latter.
[ "Texts and Concepts", "The Human Mind and Its Complexity" ]
10.1016/j.molcel.2015.03.027
Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Neuroscience and Disorders of the Nervous System", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1371/journal.pone.0041921
Dynamic expression of the translational machinery during Bacillus subtilis life cycle at a single cell level
The ability of bacteria to responsively regulate the expression of translation components is crucial for rapid adaptation to fluctuating environments. Utilizing Bacillus subtilis (B. subtilis) as a model organism, we followed the dynamics of the translational machinery at a single cell resolution during growth and differentiation. By comprehensive monitoring the activity of the major rrn promoters and ribosomal protein production, we revealed diverse dynamics between cells grown in rich and poor medium, with the most prominent dissimilarities exhibited during deep stationary phase. Further, the variability pattern of translational activity varied among the cells, being affected by nutrient availability. We have monitored for the first time translational dynamics during the developmental process of sporulation within the two distinct cellular compartments of forespore and mother-cell. Our study uncovers a transient forespore specific increase in expression of translational components. Finally, the contribution of each rrn promoter throughout the bacterium life cycle was found to be relatively constant, implying that differential expression is not the main purpose for the existence of multiple rrn genes. Instead, we propose that coordination of the rrn operons serves as a strategy to rapidly fine tune translational activities in a synchronized fashion to achieve an optimal translation level for a given condition.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
725085
Chemical proteome mining for functional annotation of disease relevant proteins
Genome sequencing projects have provided unique insights into the cellular inventory of genes and their corresponding protein products. Despite this success, a large fraction of cellular proteins remains functionally uncharacterized. Their annotation represents a major challenge for contemporary research, reaching beyond the power of bioinformatic sequence similarity searches. Thus multidisciplinary strategies consolidating chemical and biological methods are required to close this gap. We here approach the challenge by two chemical proteomic platforms that focus on disease relevant sub-fractions of the uncharacterized proteome. The first platform utilizes functionalized cofactors that exploit cognate cellular uptake systems and report specific binding of large enzyme families. The molecules will be applied to mine cellular proteomes for unknown family members with crucial roles in diseases and assign their function. The second platform exploits phosphoaspartate as an important disease-related post-translational modification. Due to low stability, this transient modification currently escapes detection by established proteomic procedures. Moreover, little is known about the enzymes that catalyze aspartate phosphorylation. We here use specific nucleophilic traps that convert phosphoaspartate into stable modifications suitable for analytic detection. In addition, the complement of currently unknown phosphodonor proteins will be identified with customized tools. With these platforms we aim to functionally annotate sub-fractions of the uncharacterized proteome and utilize our tools for the identification of new drug targets by comparative analysis of healthy and diseased cells. Finally, we apply the camouflaged molecular design strategy in the synthesis of compound libraries to screen for candidate inhibitors against selected, disease-modulating targets. The previous record of my group in chemical proteomics provides a strong basis to achieve these challenging goals.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physical and Analytical Chemical Sciences", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W2056378745
Lie Algebras with a Coalgebra Splitting
In their recent article [5], the authors endow every finite-dimensional simple complex Lie algebra g with a coalgebra structure such that the composition μ◦δ of the two structure maps δ : g −→ g⊗Cg and μ : g⊗C g −→ g coincides with the identity. Moreover, the dual algebra (g∗, δ∗) associated to the Lie coalgebra is isomorphic to (g, μ). The coalgebra map δ is given explicitly for sl(n), those for the other types are obtained via embeddings g ↪→ sl(n). The purpose of the present short note is to elicit the conceptual sources of [5], starting from the observation that the coalgebra maps defined in [5] are in fact homomorphisms of g-modules. For Lie algebras affording non-degenerate symmetric associative forms, such coalgebra maps naturally arise by dualizing the multiplication. This immediately implies the abovementioned duality, and the formulae displayed in [5, §4] can also be subsumed under our general approach. By demanding that δ be g-linear, we depart from the usual compatibility condition of a Lie bialgebra, which requires δ to be a derivation. In that case, μ ◦ δ is a derivation of g. For fields of characteristic zero, only nilpotent Lie algebras afford invertible derivations (cf. [7]), so that non-zero Lie bialgebras over such fields never satisfy μ ◦ δ = idg. Let k be a field. Given a finite-dimensional k-vector space V , we consider the k-linear maps
[ "Mathematics" ]
10.1523/JNEUROSCI.3456-16.2017
Selective Silencing Of Hippocampal Parvalbumin Interneurons Induces Development Of Recurrent Spontaneous Limbic Seizures In Mice
Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsies and is generally associated with malfunctioning of the hippocampal formation. Recently, a preferential loss of parvalbumin (PV) neurons has been observed in the subiculum of TLE patients and in animal models of TLE. To demonstrate a possible causative role of defunct PV neurons in the generation of TLE, we permanently inhibited GABA release selectively from PV neurons of the ventral subiculum by injecting a viral vector expressing tetanus toxin light chain in male mice. Subsequently, mice were subjected to telemetric EEG recording and video monitoring. Eighty-eight percent of the mice presented clusters of spike-wave discharges (C-SWDs; 40. 0 ± 9. 07/month), and 64% showed spontaneous recurrent seizures (SRSs; 5. 3 ± 0. 83/month). Mice injected with a control vector presented with neither C-SWDs nor SRSs. No neurodegeneration was observed due to vector injection or SRS. Interestingly, mice that presented with only C-SWDs but no SRSs, developed SRSs upon injection of a subconvulsive dose of pentylenetetrazole after 6 weeks. The initial frequency of SRSs declined by ∼30% after 5 weeks. In contrast to permanent silencing of PV neurons, transient inhibition of GABA release from PV neurons through the designer receptor hM4Di selectively expressed in PV-containing neurons transiently reduced the seizure threshold of the mice but induced neither acute nor recurrent seizures. Our data demonstrate a critical role for perisomatic inhibition mediated by PV-containing interneurons, suggesting that their sustained silencing could be causally involved in the development of TLE. SIGNIFICANCE STATEMENT Development of temporal lobe epilepsy (TLE) generally takes years after an initial insult during which maladaptation of hippocampal circuitries takes place. In human TLE and in animal models of TLE, parvalbumin neurons are selectively lost in the subiculum, the major output area of the hippocampus. The present experiments demonstrate that specific and sustained inhibition of GABA release from parvalbumin-expressing interneurons (mostly basket cells) in sector CA1/subiculum is sufficient to induce hyperexcitability and spontaneous recurrent seizures in mice. As in patients with nonlesional TLE, these mice developed epilepsy without signs of neurodegeneration. The experiments highlight the importance of the potent inhibitory action mediated by parvalbumin cells in the hippocampus and identify a potential mechanism in the development of TLE.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1038/ncomms4221
Strong schottky barrier reduction at au-catalyst/gaas-nanowire interfaces by electric dipole formation and fermi-level unpinning
Nanoscale contacts between metals and semiconductors are critical for further downscaling of electronic and optoelectronic devices. However, realizing nanocontacts poses significant challenges since conventional approaches to achieve ohmic contacts through Schottky barrier suppression are often inadequate. Here we report the realization and characterization of low n-type Schottky barriers (∼0. 35 eV) formed at epitaxial contacts between Au-In alloy catalytic particles and GaAs-nanowires. In comparison to previous studies, our detailed characterization, employing selective electrical contacts defined by high-precision electron beam lithography, reveals the barrier to occur directly and solely at the abrupt interface between the catalyst and nanowire. We attribute this lowest-to-date-reported Schottky barrier to a reduced density of pinning states (∼10 17 m-2) and the formation of an electric dipole layer at the epitaxial contacts. The insight into the physical mechanisms behind the observed low-energy Schottky barrier may guide future efforts to engineer abrupt nanoscale electrical contacts with tailored electrical properties.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1089/ast.2016.1557
Evaluation of the Tindouf Basin Region in Southern Morocco as an Analogue Site for Soil Geochemistry on Noachian Mars
Locations on Earth that provide insights into processes that may be occurring or may have occurred throughout martian history are often broadly deemed "Mars analog environments. " As no single locale can precisely represent a past or present martian environment, it is important to focus on characterization of terrestrial processes that produce analogous features to those observed in specific regions of Mars or, if possible, specific time periods during martian history. Here, we report on the preservation of ionic species in soil samples collected from the Tindouf region of Morocco and compare them with the McMurdo Dry Valleys of Antarctica, the Atacama Desert in Chile, the martian meteorite EETA79001, and the in situ Mars analyses from the Phoenix Wet Chemistry Laboratory (WCL). The Moroccan samples show the greatest similarity with those from Victoria Valley, Beacon Valley, and the Atacama, while being consistently depleted compared to University Valley and enriched compared to Taylor Valley. The NO3/Cl ratios are most similar to Victoria Valley and Atacama, while the SO4/Cl ratios are similar to those from Beacon Valley, Victoria Valley, and the Atacama. While perchlorate concentrations in the Moroccan samples are typically lower than those found in samples of other analog sites, conditions in the region are sufficiently arid to retain oxychlorines at detectable levels. Our results suggest that the Tindouf Basin in Morocco can serve as a suitable analogue for the soil geochemistry and subsequent aridification of the Noachian epoch on Mars.
[ "Earth System Science", "Universe Sciences" ]
10.1038/s41556-018-0140-1
Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome CRISPR–Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance. Mechanistically, we show that C20orf196 and FAM35A form a complex, ‘Shieldin’ (SHLD1/2), with FAM35A interacting with single-stranded DNA through its C-terminal oligonucleotide/oligosaccharide-binding fold region. We establish that Shieldin acts as the downstream effector of 53BP1/RIF1/MAD2L2 to promote DNA double-strand break (DSB) end-joining by restricting DSB resection and to counteract homologous recombination by antagonizing BRCA2/RAD51 loading in BRCA1-deficient cells. Notably, Shieldin inactivation further sensitizes BRCA1-deficient cells to cisplatin, suggesting how defining the SHLD1/2 status of BRCA1-deficient tumours might aid patient stratification and yield new treatment opportunities. Highlighting this potential, we document reduced SHLD1/2 expression in human breast cancers displaying intrinsic or acquired PARP-inhibitor resistance.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
EP 2013055679 W
COMPATIBILITY CONTROL OF COMPONENTS CONNECTED TO WORK MACHINE
The present invention relates to a method for controlling compatibility of components connected to a work machine comprising a control system. A compatibility check request message is transmitted to a server in response to detecting that identification information of a component attached to the work machine is unknown. The server comprises compatibility information on component identifiers allowed for a plurality of work machines. A compatibility check response message is receive from the server, the response message comprising compatibility information associated with the work machine. Use of the component in the work machine is allowed or rejected on the basis of the compatibility information in the response message.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1093/cercor/bhy330
Waves of maturation and senescence in micro-structural MRI markers of human cortical myelination over the lifespan
Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.
[ "Neuroscience and Disorders of the Nervous System", "Physiology in Health, Disease and Ageing" ]
622627
Improving the preparedness of health systems to reduce mental health and psychosocial concerns resulting from the covid-19 pandemic
The mission of RESPOND is 1) to identify critical resilience factors and specific vulnerable groups at risk of immediate and long-term adverse mental health impact of the COVID-19 pandemic; 2) To improve the resilience, wellbeing and mental health of frontline health and care workers and other vulnerable groups by implementing scalable World Health Organization (WHO) programmes, and 3) to steer future policy decisions by understanding and disentangling the effects of the COVID-19 pandemic and different public health containment and subsequently relaxation strategies on mental health and wellbeing in vulnerable groups across Europe’s different health systems. RESPOND is centred around core questions regarding the short and long-term impacts of the pandemic on mental health and health inequalities on vulnerable groups within the general population, including frontline workers. In the first immediate delivery phase, an impressive set of existing longitudinal datasets are examined for resilience factors and risk factors. Furthermore, the responsiveness of health systems and identification of best practice responses that protect resilience, mental health and wellbeing are assessed in eight EU countries. The long-terms effects are determined of the pandemic and the control measures on demand for (mental) health services in health registers in Sweden, Lombardy and Barcelona and the scalable WHO SH+/PM+ stepped care programmes adapted for COVID-19 will be implemented and evaluated both in frontline workers and vulnerable groups. RESPOND provides policy recommendations within 3 months on vulnerability factors for developing poor mental health resulting from current containment and mitigation measures. Further lessons learnt and evidence-based policy recommendations will be made available during the project’s lifetime through Policy Briefs in month 6, 12, 18, 24 and 36 for immediate consideration and use by all EU member states.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "The Human Mind and Its Complexity", "Institutions, Governance and Legal Systems" ]
819627
Beyond Light Imaging: High-Rate Single-Photon Detection in Four Dimensions
Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required. Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit. As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.
[ "Fundamental Constituents of Matter", "Systems and Communication Engineering" ]
10.1080/14686996.2016.1244474
A Study Of The Optical And Polarisation Properties Of Ingan Gan Multiple Quantum Wells Grown On A Plane And M Plane Gan Substrates
In this paper we report on a comparative study of the low temperature emission and polarisation properties of InGaN/GaN quantum wells (QWs) grown on nonpolar a-plane and m-plane free-standing bulk GaN substrates where the In content varied from 0. 14 to 0. 28 in the m-plane series and 0. 08 to 0. 21 for the a-plane series. The low temperature photoluminescence spectra from both sets of samples are very broad with full width at half-maximum height increasing from 81 to 330 meV as the In fraction increases. Comparative photoluminescence excitation spectroscopy indicates that the recombination mainly involves strongly localised carriers. At a temperature of 10 K the degree of linear polarisation of the a-plane samples is much smaller than of the m-plane counterparts and also varies across the spectrum. From polarisation-resolved photoluminescence excitation spectroscopy we measured the energy splitting between the lowest valence sub-band states to lie in the range of 23-54 meV for both a-and m-plane samples in which we could observe distinct exciton features in the polarised photoluminescence excitation spectroscopy. Thus, the thermal occupation of a higher valence subband cannot be responsible for the reduction of the degree of linear polarisation. Time-resolved spectroscopy indicates that in a-plane samples there is an extra emission component which at least partly responsible for the reduction in the degree of linear polarisation.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1016/j.bbabio.2015.08.007
The origin of the unusual Q<inf>y</inf> red shift in LH1-RC complexes from purple bacteria Thermochromatium tepidum as revealed by Stark absorption spectroscopy
Native LH1-RC of photosynthetic purple bacteria Thermochromatium (Tch. ) tepidum, B915, has an ultra-red BChl a Qy absorption. Two blue-shifted complexes obtained by chemical modification, B893 and B882, have increasing full widths at half maximum (FWHM) and decreasing transition dipole oscillator strength. 77 K Stark absorption spectroscopy studies were employed for the three complexes, trying to understand the origin of the 915 nm absorption. We found that Tr(δα) and |δμ| of both Qy and carotenoid (Car) bands are larger than for other purple bacterial LH complexes reported previously. Moreover, the red shifts of the Qy bands are associated with (1) increasing Tr(δα) and |δμ| of the Qy band, (2) the red shift of the Car Stark signal and (3) the increasing |δμ| of the Car band. Based on the results and the crystal structure, a combined effect of exciton-charge transfer (CT) states mixing, and inhomogeneous narrowing of the BChl a site energy is proposed to be the origin of the 915 nm absorption. CT-exciton state mixing has long been found to be the origin of strong Stark signal in LH1 and special pair, and the more extent of the mixing in Tch. tepidum LH1 is mainly the consequence of the shorter BChl-BChl distances. The less flexible protein structure results in a smaller site energy disorder (inhomogeneous narrowing), which was demonstrated to be able to influence |δμ| and absorption.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
W1966174625
Quantitative assessment of the diagnostic role of human telomerase activity from pancreatic juice in pancreatic cancer
Many studies have shown that human telomerase activity could play potential role as a diagnostic biomarker of pancreatic cancer (PaC). The aim of this meta-analysis is to summarize the clinical value of human telomerase activity in the diagnosis of PaC. Eligible studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Sci Verse, Science Direct, Scopus, BioMed Central, Biosis previews, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang databases were searched concerning the diagnostic value of human telomerase activity in PaC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratio (DOR) for human telomerase activity in the diagnosis of PaC were pooled. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2) test. Meta-Disc 1.4 and Stata 12.0 software were used to analyze the data. Nine studies with a total 186 PaC patients and 132 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score ≥10). The summary estimate was 0.83 (95 % confidence interval (CI), 95 % CI = 0.77-0.88) for sensitivity and 0.72 (95 % CI = 0.64-0.79) for specificity. The positive likelihood (PLR), negative likelihood (NLR), and diagnostic odds (DOR) ratios were 3 (95 % CI = 1.67-5.41), 0.25 (95 % CI = 0.13-0.46), and 3 (95 % CI = 4.91-43.23), respectively. The area under the summary ROC curve (AUC) and Q* index for the diagnosis of PaC were 0.88 and 0.81, respectively. Our study demonstrates that telomerase could be a useful tumor marker for PaC diagnosis. Although more studies are needed to highlight the theoretical strengths, these results will provide theoretical basis for bringing telomerase activity detection into PaC screening plan.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]