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259204
Systems Chemistry from Bottom Up: Switching, Gating and Oscillations in Non Enzymatic Peptide Networks
The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Systems and Communication Engineering" ]
interreg_3188
A cross-border pattern of ecosustainable tourism to enhance archaeological, religious and popular traditions sites connected with the historical memory of the population in the municipality of San Michele al Tagliamento
The project of cross-border cooperation in the field of eco-sustainable tourism aims at learning about and enhancing the landscape, history and culture of a wide geographical area which developed between the rivers Tagliamento and Isonzo. The first part of the project concerns the census and the historical documentation of the sites to be catalogued, the overview, the photo/video survey and the creation of computerized files. Then the itineraries will be defined; guides and information material will be published, and made available also on the Town’s website. The objective consists in the promotion of three new itineraries along the riverways between the two regions, to favour a slow (nautical, cycling-pedestrian) sustainable mobility mainly in rural milieus. The project aims at retrieving the Roman and Medieval historical heritage, rediscovering the most interesting architectural items of the Venetian villas in the area, and learning more about the rural towns and villages. The itineraries created are: “From San Tommaso to Palazzo Braida. Towards the Sea along the Tagliamento”, “From Chiesa di San Nicolo’ to the Casoni. From the Tagliamento to the hinterland”, and “From the lighthouse of Bibione to the house of the valley. Between the valleys and the sea”. All itineraries were equipped with specially designed signage. In order to leave a memory of this human and professional experience, a publication was prepared entitled “Artistic, historical and environmental itineraries” consisting of two volumes, and lastly a CD-ROM is available presenting the itineraries identified through this study.
[ "Human Mobility, Environment, and Space", "The Study of the Human Past" ]
10.1371/journal.pone.0090695
Improving the adaptability of simulated evolutionary swarm robots in dynamically changing environments
One of the important challenges in the field of evolutionary robotics is the development of systems that can adapt to a changing environment. However, the ability to adapt to unknown and fluctuating environments is not straightforward. Here, we explore the adaptive potential of simulated swarm robots that contain a genomic encoding of a bio-inspired gene regulatory network (GRN). An artificial genome is combined with a flexible agent-based system, representing the activated part of the regulatory network that transduces environmental cues into phenotypic behaviour. Using an artificial life simulation framework that mimics a dynamically changing environment, we show that separating the static from the conditionally active part of the network contributes to a better adaptive behaviour. Furthermore, in contrast with most hitherto developed ANN-based systems that need to re-optimize their complete controller network from scratch each time they are subjected to novel conditions, our system uses its genome to store GRNs whose performance was optimized under a particular environmental condition for a sufficiently long time. When subjected to a new environment, the previous condition-specific GRN might become inactivated, but remains present. This ability to store 'good behaviour' and to disconnect it from the novel rewiring that is essential under a new condition allows faster re-adaptation if any of the previously observed environmental conditions is reencountered. As we show here, applying these evolutionary-based principles leads to accelerated and improved adaptive evolution in a non-stable environment.
[ "Computer Science and Informatics", "Systems and Communication Engineering", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1109/CDC.2011.6161254
A Simple Recursive Algorithm For Learning A Monotone Wiener System
This paper studies a recursive identification method (i. e. an adaptive filter, or online learning algorithm) - termed the RANKTRON - for learning a Monotone Wiener model from observed input-output pairs. Such a model consists of a sequence of an unknown Linear Time-Invariant (LTI) dynamic model, followed by an unknown monotone (in- or decreasing) static nonlinear function. The main contribution is the introduction of a technical argument which establish worst-case performance of the proposed algorithm. The same tool is then used to derive properties in case the Monotone Wiener assumption only holds approximatively, and to the case where the output nonlinearity is a quantization function. An application of the RANKTRON is reported for the identification of a 20e order LTI based on quantized observations, using a mere O(1000) samples.
[ "Computer Science and Informatics", "Mathematics" ]
Q2691432
Subvención de capital de explotación para Zalchem SJ
El proyecto se refiere al apoyo del empresario a proporcionar liquidez financiera y apoyo a las actividades actuales debido a las dificultades financieras experimentadas por el empresario como consecuencia del brote de COVID-19. Ayuda financiera concedida en el marco del programa n.º SA.57015 (2020/N)
[ "Individuals, Markets and Organisations" ]
10.1007/s10585-018-9896-8
Potential impact of invasive surgical procedures on primary tumor growth and metastasis
Surgical procedures such as tumor resection and biopsy are still the gold standard for diagnosis and (determination of) treatment of solid tumors, and are prognostically beneficial for patients. However, growing evidence suggests that even a minor surgical trauma can influence several (patho) physiological processes that might promote postoperative metastatic spread and tumor recurrence. Local effects include tumor seeding and a wound healing response that can promote tumor cell migration, proliferation, differentiation, extracellular matrix remodeling, angiogenesis and extravasation. In addition, local and systemic immunosuppression impairs antitumor immunity and contributes to tumor cell survival. Surgical manipulation of the tumor can result in cancer cell release into the circulation, thus increasing the chance of tumor cell dissemination. To prevent these undesired effects of surgical interventions, therapeutic strategies targeting immune response exacerbation or alteration have been proposed. This review summarizes the current literature regarding these local, systemic and secondary site effects of surgical interventions on tumor progression and dissemination, and discusses studies that aimed to identify potential therapeutic approaches to prevent these effects in order to further increase the clinical benefit from surgical procedures.
[ "Immunity, Infection and Immunotherapy", "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
EP 82103462 A
Method of welding titanium alloy parts with titanium insert.
A method of welding opposite end surfaces of two titanium alloy parts (10, 12) kept in alignment by a high energy-density welding process such as electron beam welding, laser beam welding or TIG arc welding, characterized by closely interposing an insert member (14) of either practically pure titanium or Ti-Al binary alloy containing up to 3 Wt% of AI. Owing to thorough alloying of the inserted titanium (14) with the constituents of the fused base metal (10, 12), the weld metal (16) in a weld joint obtained by this method is sufficiently high in both strength and toughness. By an optional postwelding heat treatment, the strength of the weld metal (16) can further be enhanced.
[ "Materials Engineering", "Products and Processes Engineering" ]
307286
The Structure of the Extra Dimensions of String Theory
String theory predicts the existence of several spatial dimensions in addition to the three of our everyday experience. The space spanned by these dimensions might be small enough to have escaped detection so far. The aim of this project is to characterize which spaces are allowed by the dynamics of the theory, and what physics they give rise to. A few years ago, I discovered a reformulation of supergravity in terms of differential forms, based on the so-called generalized complex geometry. This method was originally limited to string theory vacuum solutions, and over the years it has permitted to find many of them, often with applications to AdS/CFT. Recently, I was able to extend it to deal with any kind of spacetime dependence; this will allow to probe the choice of extra dimensions more extensively, for example by studying black hole solutions. It will help single out interesting geometries for the extra dimensions, even before one sets out to understand the effective four-dimensional Lagrangian that would result from compactifying string theory on it. Moreover, I plan to extend the method even further, to deal with controlled supersymmetry breaking. That would open the possibility of producing systematically vacuum solutions which have a positive cosmological constant. The vacua obtained in this way would be fully classical, and under better control than current models.
[ "Fundamental Constituents of Matter", "Mathematics" ]
679627
Galaxy evolution in dense environments
The Universe around us is populated with galaxies, each containing from millions to tens of billions of individual stars. Far from being immutable, galaxies undergo profound changes as they age. Their evolution depends on their position in the cosmic web, a network of sheets and filaments of matter that stretches across the entire Universe. The goal of FORNAX is to study the evolution of galaxies in the densest regions of the cosmic web, galaxy clusters. In these regions, a number of physical processes are thought to make galaxies lose their cold gas – the material from which new stars are born – and change their appearance dramatically. I will study these processes in action by observing the flow of cold gas in and out of galaxies living inside an important, nearby cluster of galaxies: Fornax. I will observe Fornax for 2,450 hours with MeerKAT, a new, state-of-the-art radio telescope precursor of the Square Kilometre Array. Thanks to the unprecedented combination of sensitivity, resolution and sky-coverage of my survey, I will reveal the most subtle signs of the removal of gas from galaxies, I will detect the smallest gas-bearing galaxies in the cluster, and I will hunt the elusive cold gas which, according to cosmological theories, floats in the space between galaxies along the filaments of the cosmic web.
[ "Universe Sciences", "Systems and Communication Engineering" ]
10.1097/MPG.0000000000001220
Childhood Obesity Current Situation And Future Opportunities
Purpose of review The early origins of overweight and obesity and the opportunities for early prevention are explored. Recent findings Overweight and obesity prevalence globally has increased at an alarming rate. No single intervention can halt the rise of the obesity epidemic. Particular attention is given to exploring causative factors and preventive measures in early life, when biological determinants of risk trajectories, feeding behaviour and dietary preferences are shaped. Some lifestyle and nutrition modifications in pregnancy and infancy can reduce subsequent obesity risk. Also postnatal infant gut colonisation may modify later obesity risk, but currently available evidence does not allow firm conclusions. Surprisingly, about 3. 2 times more systematic reviews (SR) than randomized clinical trials (RCTs) were published on "probiotics" and health, and even 7. 9 times more SR than RCTs on "probiotics" and obesity, which is not helpful. Summary Multiple research opportunities exist for exploring the early origins of obesity to contribute towards halting the rise in obesity prevalence. Exploring the early development of the microbiome in its complexity, its dependence on dietary and other exogenous factors, and its metabolic and regulatory functions is promising. Meaningful progress for obesity prevention can most likely be achieved by combining several strategies.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1117/12.2233274
The Qacits Pointing Sensor From Theory To On Sky Operation On Keck Nirc2
Small inner working angle coronagraphs are essential to benefit from the full potential of large and future extremely large ground-based telescopes, especially in the context of the detection and characterization of exoplanets. Among existing solutions, the vortex coronagraph stands as one of the most effective and promising solutions. However, for focal-plane coronagraph, a small inner working angle comes necessarily at the cost of a high sensitivity to pointing errors. This is the reason why a pointing control system is imperative to stabilize the star on the vortex center against pointing drifts due to mechanical flexures, that generally occur during observation due for instance to temperature and/or gravity variations. We have therefore developed a technique called QACITS1 (Quadrant Analysis of Coronagraphic Images for Tip-tilt Sensing), which is based on the analysis of the coronagraphic image shape to infer the amount of pointing error. It has been shown that the flux gradient in the image is directly related to the amount of tip-tilt affecting the beam. The main advantage of this technique is that it does not require any additional setup and can thus be easily implemented on all current facilities equipped with a vortex phase mask. In this paper, we focus on the implementation of the QACITS sensor at Keck/NIRC2, where an L-band AGPM has been recently commissioned (June and October 2015), successfully validating the QACITS estimator in the case of a centrally obstructed pupil. The algorithm has been designed to be easily handled by any user observing in vortex mode, which is available for science in shared risk mode since 2016B.
[ "Universe Sciences", "Systems and Communication Engineering" ]
222552
Isolation of rare circulating tumor cells
In 2013 I was awarded an ERC consolidator grant to pursue a novel cancer targeting concept using a recombinant malaria protein. As an ERC grantee I verified the malaria protein (rVAR2) binds to this distinct cancer expressed molecule (CSA) in hundreds of cancer cell lines and thousands of tissue biopsies. Our research demonstrate a pivotal role of CSA in cancer cell migration and thus in the formation of metastasis. Circulating tumor cells (CTCs) are cancer cells escaping the primary tumor with the capacity to settle and form a metastasis in distant organs. Isolation of CTC is thus a very attractive non-invasive measure of the stage of a given cancer and provides the opportunity to do direct phenotypic analyses. However CTCs are in most cases very rare (10 cells pr 1ml blood) and does not uniformly distinguish themselves from normal blood cells. Our preliminary data show that rVAR2 very effectively can be used to isolate CTCs from diverse types of cancer with unprecedented specificity and sensitivity. Such a tool could have wide impact for cancer patients because it could sharpen diagnosis, increase prognostic ability, monitor drug efficacy and facilitate molecular characterization of individual cancers with implications for personalized medicine and basic cancer research. The aim of the ERC PoC project is to A) prepare for establishment of a separate company with a strategic product plan and B) further develop and validate the methodology enabling diagnosis, prognosis and guide treatment.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1002/anie.201601564
Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics
The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.
[ "Synthetic Chemistry and Materials", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W4220916797
A case of Grover disease treated with Dupilumab: Just serendipity or a future perspective?
Dermatologic TherapyAccepted Articles e15429 LETTER A case of Grover disease treated with Dupilumab: just serendipity or a future perspective? Francesca Barei, Corresponding Author Francesca Barei [email protected] orcid.org/0000-0002-7188-7310 UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy Correspondence Francesca Barei MD, U.O. Dermatologia, via Pace 9, 20122 Milano, Italy, Email: [email protected] for more papers by this authorSara Torretta, Sara Torretta Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dept. of Clinical Sciences and Community Health, University of Milan, Milan, ItalySearch for more papers by this authorNicole Morini, Nicole Morini UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalySearch for more papers by this authorSilvia Ferrucci, Silvia Ferrucci UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalySearch for more papers by this author Francesca Barei, Corresponding Author Francesca Barei [email protected] orcid.org/0000-0002-7188-7310 UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy Correspondence Francesca Barei MD, U.O. Dermatologia, via Pace 9, 20122 Milano, Italy, Email: [email protected] for more papers by this authorSara Torretta, Sara Torretta Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dept. of Clinical Sciences and Community Health, University of Milan, Milan, ItalySearch for more papers by this authorNicole Morini, Nicole Morini UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalySearch for more papers by this authorSilvia Ferrucci, Silvia Ferrucci UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalySearch for more papers by this author First published: 08 March 2022 https://doi.org/10.1111/dth.15429 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/dth.15429. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future.e15429 RelatedInformation
[ "Immunity, Infection and Immunotherapy", "Prevention, Diagnosis and Treatment of Human Diseases" ]
US 2018/0052966 W
PROCESS FOR HYDROLYSIS OF OLIGOSACCHARIDES
Provided is a method comprising (a) providing a hydrolysis composition of at least 20 wt% of sugar equivalents, wherein the hydrolysis composition comprises a first oligosaccharide, water, optionally a soluble aromatic compound, (b) contacting the hydrolysis composition with a catalyst in a first reactor to hydrolyze at least a portion of the first oligosaccharide to form a first product composition comprising a first monosaccharide and a second oligosaccharide, (c) separating the first monosaccharide from the first product composition to form a second product composition comprising the second oligosaccharide, wherein at least a portion of the second oligosaccharide is a reversion sugar, and (d) converting via a further hydrolysis step at least a portion of the second oligosaccharide to form a third product composition comprising a second monosaccharide.
[ "Products and Processes Engineering", "Physical and Analytical Chemical Sciences" ]
interreg_2740
Project of Offshore Wind Energy: Research, Experimentation, Development
POWERED aims to define a set of strategies and shared methods for the development of the off-shore wind energy in all the Countries overlooking the Adriatic Sea. Such energetic choice could allow a rapid increase of installations, thanks to the reduction of the problems related to landscape topic that are frequently the main obstacles to the creation of wind parks in high density population territories or in areas with high historical or landscape value. Also the problems related to the transport of the wind turbines of big size should be reduced, especially in Countries like Italy in which the problem of connection between the main and the suburban roads is important, because of the small dimension of the roadway. Industrial ports that overlooking the Adriatic Sea could be assume a decisive role in the development process, becoming a marshalling but also productive areas of the technological components. The main objective of the project is drafting guide lines for the realization of off-shore wind parks in the Adriatic Sea compatible with the planning and conservation policy shared among the project partners. In parallel will be identified development Sea basins for the energetic technology above mentioned. It will allow the defining of the characteristics for a project of electric submarine connection network that will enormously facilitate the exchange of energy power between Countries. The achievement of the project’s objectives will be possible thanks to the study concerning the wind resources on the Adriatic Basin, the study will be developed through numerical process and will be validated through testing method. Such validation will be possible thanks to the installation of a network of coastal weather stations and of, at least, ones marine. Such network, at he end of the project, will be functioning and will support weather forecast services.
[ "Products and Processes Engineering", "Earth System Science" ]
10.1175/jcli-d-18-0845.1
A Positive Iris Feedback: Insights from Climate Simulations with Temperature-Sensitive Cloud–Rain Conversion
AbstractEstimates for equilibrium climate sensitivity from current climate models continue to exhibit a large spread, from 2. 1 to 4. 7 K per carbon dioxide doubling. Recent studies have found that the treatment of precipitation efficiency in deep convective clouds—specifically the conversion rate from cloud condensate to rain Cp—may contribute to the large intermodel spread. It is common for convective parameterization in climate models to carry a constant Cp, although its values are model and resolution dependent. In this study, we investigate how introducing a potential iris feedback, the cloud–climate feedback introduced by parameterizing Cp to increase with surface temperature, affects future climate simulations within a slab ocean configuration of the Community Earth System Model. Progressively stronger dependencies of Cp on temperature unexpectedly increase the equilibrium climate sensitivity monotonically from 3. 8 to up to 4. 6 K. This positive iris feedback puzzle, in which a reduction in cirrus clouds increases surface temperature, is attributed to changes in the opacity of convectively detrained cirrus. Cirrus clouds reduced largely in ice content and marginally in horizontal coverage, and thus the positive shortwave cloud radiative feedback dominates. The sign of the iris feedback is robust across different cloud macrophysics schemes, which control horizontal cloud cover associated with detrained ice. These results suggest a potentially strong but highly uncertain connection among convective precipitation, detrained anvil cirrus, and the high cloud feedback in a climate forced by increased atmospheric carbon dioxide concentrations.
[ "Earth System Science", "Physical and Analytical Chemical Sciences" ]
172151
Clinical validation of trop-2 as a serum biomarker for monitoring of disease-course in patients affected by breast and colon cancer
A critical need in cancer care is the possibility to monitor tumour progression, through non-invasive techniques, to recognize relapses and/or metastases at a very early stage. The measurement of tumour biomarkers circulating into the bloodstream is a feasible way, as it can give indications also on patients’ response to therapeutic treatments, thus enabling the oncologist to pursue a precision-medicine strategy. In patients affected by breast and colon cancer, most serum biomarkers employed in the clinical practice have poor specificity and sensitivity to be used as monitoring tool of the cancer progression. Oncoxx Biotech has collected strong experimental data demonstrating that the transmembrane receptor Trop-2 drives progression of several tumour types. It has also been shown that Trop-2 is a determinant of breast cancer survival, and it is released in the bloodstream in patients with breast and colorectal cancer. In this respect, the results achieved in a preliminary clinical study have shown that all higher-than-baseline levels of circulating Trop-2 identify breast cancers with 100% specificity and 80% sensitivity and colon cancer with 100% of specificity and 74% of sensitivity. Therefore, scope of the ThruBlood project is to validate Trop-2 as a serum biomarker for monitoring disease-course in patients with breast and colon cancer. During Phase 1 we will: 1) assess the scientific feasibility of the proposed biomarker by extending the population of serum samples to analyse; 2) design the Clinical Validation Study to pursue in Phase2; 3) validate a standardized procedure for accurate measurement of the serum Trop-2 levels using a proprietary device (ICONA, patented by the applicant) with aim of providing high-throughput procedures for serum biomarker detection; 4) analyse and validate the business opportunity represented by the introduction of the ThruBlood assay in the current procedure adopted for surveillance of cancer diagnosed and treated patients.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1523/JNEUROSCI.6265-10.2011
Group I mGluR agonist-evoked long-term potentiation in hippocampal oriens interneurons
Several subtypes of interneurons in the feedback circuit in stratum oriens of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) at glutamatergic synapses made by local pyramidal neurons. LTP has been reported with both "Hebbian" and "anti-Hebbian" induction protocols, wherehigh-frequencypresynaptic stimulation is paired with either postsynaptic depolarization or hyperpolarization. Do these phenomena represent distinct forms of plasticity, dependent on group I metabotropic receptors (mGluRs) and rectifying Ca2+-permeable AMPA receptors, respectively? Blockade of either mGluR1 or mGluR5 prevented anti-Hebbian LTP induction in stratum oriens interneurons in rat hippocampal slices. Exogenous activation of group I mGluRs by the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was unable to induce LTP on its own, and instead depressed excitatory transmission. However, when paired with postsynaptic hyperpolarization, DHPG or the group I metabotropic receptor (mGluR5)-selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) elicited a delayed long-lasting potentiation, which was accompanied by a decrease in paired-pulse facilitation. Anti-Hebbian LTP occluded the effect of DHPG paired with hyperpolarization, implying that the induction cascades triggered by both conjunctions of stimuli converge on common expression mechanisms.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1038/s41598-018-29869-7
Blue pigmentation of neustonic copepods benefits exploitation of a prey-rich niche at the air-sea boundary
The sea-surface microlayer (SML) at the air-sea interface is a distinct, under-studied habitat compared to the subsurface and copepods, important components of ocean food webs, have developed key adaptations to exploit this niche. By using automated SML sampling, high-throughput sequencing and unmanned aerial vehicles, we report on the distribution and abundance of pontellid copepods in relation to the unique biophysicochemical signature of the SML. We found copepods in the SML even during high exposure to sun-derived ultraviolet radiation and their abundance was significantly correlated to increased algal biomass. We additionally investigated the significance of the pontellids’ blue pigmentation and found that the reflectance peak of the blue pigment matched the water-leaving spectral radiance of the ocean surface. This feature could reduce high visibility at the air-sea boundary and potentially provide camouflage of copepods from their predators.
[ "Earth System Science", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1038/ng.3447
Domestication selected for deceleration of the circadian clock in cultivated tomato
The circadian clock is a critical regulator of plant physiology and development, controlling key agricultural traits in crop plants. In addition, natural variation in circadian rhythms is important for local adaptation. However, quantitative modulation of circadian rhythms due to artificial selection has not yet been reported. Here we show that the circadian clock of cultivated tomato (Solanum lycopersicum) has slowed during domestication. Allelic variation of the tomato homolog of the Arabidopsis gene EID1 is responsible for a phase delay. Notably, the genomic region harboring EID1 shows signatures of a selective sweep. We find that the EID1 allele in cultivated tomatoes enhances plant performance specifically under long day photoperiods, suggesting that humans selected slower circadian rhythms to adapt the cultivated species to the long summer days it encountered as it was moved away from the equator.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.copbio.2015.12.009
Superresolution microscopy with transient binding
For single-molecule localization based superresolution, the concentration of fluorescent labels has to be thinned out. This is commonly achieved by photophysically or photochemically deactivating subsets of molecules. Alternatively, apparent switching of molecules can be achieved by transient binding of fluorescent labels. Here, a diffusing dye yields bright fluorescent spots when binding to the structure of interest. As the binding interaction is weak, the labeling is reversible and the dye ligand construct diffuses back into solution. This approach of achieving superresolution by transient binding (STB) is reviewed in this manuscript. Different realizations of STB are discussed and compared to other localization-based superresolution modalities. We propose the development of labeling strategies that will make STB a highly versatile tool for superresolution microscopy at highest resolution.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
3741835
Physiological significance of the glucocorticoid and mineralocorticoid receptor signalling in the innate immune system
Glucocorticoids, such as cortisol, play an essential role in our stress response. Cortisol signals through two receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), and it has profound effects on the immune system. To date, much of the research on cortisol action has focused on the function of GR, but almost no work has been done on the function of MR. My main aim is to unravel the role of MR in mediating the effects of cortisol on the immune response, and I would like to answer two questions: 1) How does MR activation modulate the inflammatory response? 2) How do MR and GR functionally interact to alter gene transcription? I will use an interdisciplinary approach. The first question will be answered using the zebrafish animal model, and I will determine the role of MR in wounding-induced leukocyte migration in zebrafish larvae and study the mechanism of action of MR in activated macrophages. The second question will be answered using cultured macrophages, and I will determine the occurrence of MR/GR heterodimers using biophysical approaches, and establish a functional role of the heterodimers. The outcome of this project will have a considerable impact on the current paradigm of glucocorticoid action in the immune system, and extend our understanding of the molecular actions of immune-modulating glucocorticoid drugs. My training objectives are: 1) Broadening my expertise in endocrine research using the zebrafish model system. 2) Expanding my toolbox using cell culture-based approaches and biophysics. 3) Developing complementary skills required for the management and organization of an academic research group. Furthermore, I will strengthen my scientific track record and network. The project will be performed at the Institute of Biology of Leiden University, and implementation of the project in that environment will ensure a unique position for me to run this project successfully, receive appropriate training and advance my career.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2774324248
A time series analysis of the relationship between manufacturing, economic growth and employment in South Africa
Manufacturing provides a platform for innovation, job creation, investment and overall economic progression. South Africa has the potential to be a manufacturing destination of choice. However in the previous decade, this country’s manufacturing sector has been declining, making an insufficient contribution to the country’s Gross Domestic Product (GDP) and employment. The study had the aim of establishing the relationship between the manufacturing sector, economic output and employment in South Africa post-1994. Secondary data was collected for 84 quarters from 1994 Q1 to 2015 Q4. The Vector Autoregressive (VAR) model together with a multivariate cointegration approach were used to analyze the data.  The co-integration test results indicated that the manufacturing sector has a positive long-run relationship with GDP and employment. However, the relationship is only significant with GDP; it is non-significant with employment. The Vector Error Correction Model (VECM) results established that there were no short-run relationships between the variables. The absence of such relationships was confirmed by the Granger causality test. The final results of this study indicated that an increase in manufacturing results in GDP growth, while it has the potential to create an enabling environment for employment creation.
[ "Individuals, Markets and Organisations", "Products and Processes Engineering" ]
10.1016/j.immuni.2012.10.016
Conventional and Monocyte-Derived CD11b<sup>+</sup> Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen
Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b+ monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b+ cDCs but not CD103+ cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l-/- mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b+ cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.
[ "Immunity, Infection and Immunotherapy", "Cell Biology, Development, Stem Cells and Regeneration" ]
W2154443791
Modeling of specific structure crystallization coupling with dissolution
In this paper, the research framework for specific structure crystallization modeling has been proposed in which four steps are required in order to investigate the rigorous crystallization modeling by thermodynamics. The first is the activity coefficient model of the solution, the second is Solid-Liquid equilibrium, the third and fourth are the dissolution and crystallization kinetics modeling, respectively. Our investigations show that the mechanisms of complex structure formation and microphase transition can be analyzed by combining the dissolution and crystallization kinetics modeling. Moreover, the formation mechanism of the porous KCl has been analyzed, which may provide a reference for the porous structure formation in the advanced material synthesis.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Materials Engineering" ]
853064
Hybrid Electrocatalysts Inspired by the Nitrogenase Enzyme
Artificial nitrogen reduction to ammonia using the Haber-Bosch process directly supports half of the global food production and accounts for 2% of the global energy consumption. This large consumption of energy originates mostly from the use of H2 (derived from fossil fuels) as a reductant and from the high pressure and temperature required to undertake the Haber-Bosch process. Electrochemical synthesis of ammonia, using a proton and electron source combined with an electrocatalyst at room temperature to reduce N2, thus presents an appealing, energy-efficient alternative. However, despite years of research, the few currently available catalysts have very limited efficiency in N2 electroreduction. Drawing inspiration from biochemistry and using the tools of coordination chemistry, catalysis and surface chemistry, this project will explore an original strategy to develop catalysts for the reduction of N2 inspired by the nitrogenase enzyme. Motivated by the recent discovery of two unique moieties in the nitrogenase cofactor – the presence of a µ6-carbide moiety and a Mo(III) center – and of the increased understanding of substrate pathways in the nitrogenase protein structure, the goal of HEINE is to design new hybrid catalysts based on the immobilisation of accurate mimics of the nitrogenase active sites onto heterogeneous supports used to generate properties analogous of the protein scaffold (hydrophobicity, proton relays, etc.). This will provide us with novel ways to develop functional electrocatalysts for N2 reduction in ambient conditions, combining the activity of traditional solid-state systems, with the selectivity of molecular catalysts. By identifying and reproducing the parameters responsible for the unique activity of nitrogenase enzymes, HEINE will yield invaluable information on nature’s routes to N2 reduction and will pave the way towards a new generation of electrocatalysts able to promote this reaction.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Materials Engineering" ]
EP 2014060979 W
CLOTHING WIRE FOR A ROLLER OF A CARDING MACHINE
The invention relates to a clothing wire (13) for a clothing roller (10) of a carding machine, the clothing wire (13) extending in a wire longitudinal direction (1) and having a base segment (14), which is thicker transversely to the wire longitudinal direction (1). A leaf segment (15), which is narrower compared to the base segment (14), protrudes from the base segment (14). A plurality of teeth (28) is formed on the leaf segment (15) along the clothing wire (13) in the wire longitudinal direction (1). Each tooth (28) has two leaf segment lateral surfaces (15a, 15b) adjoining the base segment. On at least one of the leaf segment lateral surfaces (15a, 15b), at least one projection (24) is formed on each tooth (28). The cross-sectional profile of the projection (24) is asymmetric and preferably has the contour of a nose. The design of the clothing wire (13) results in a homogenization or parallelization of the fibers, with little wear of the clothing wire (13) and less damages to the fibers.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1098/rsos.172066
Chimpanzee quiet hoo variants differ according to context
In comparative studies of evolution of communication, the function and use of animal quiet calls have typically been understudied, despite that these signals are presumably under selection like other vocalizations, such as alarm calls. Here, we examine vocalization diversification of chimpanzee quiet ‘hoos’ produced in three contexts—travel, rest and alert—and potential pressures promoting diversification. Previous playback and observational studies have suggested that the overarching function of chimpanzee hoos is to stay in contact with others, particularly bond partners. We conducted an acoustic analysis of hoos using audio recordings from wild chimpanzees ( Pan troglodytes schweinfurthii ) of Budongo Forest, Uganda. We identified three acoustically distinguishable, context-specific hoo variants. Each call variant requires specific responses from receivers to avoid breaking up the social unit. We propose that callers may achieve coordination by using acoustically distinguishable calls, advertising their own behavioural intentions. We conclude that natural selection has acted towards acoustically diversifying an inconspicuous, quiet vocalization, the chimpanzee hoo. This evolutionary process may have been favoured by the fact that signallers and recipients share the same goal, to maintain social cohesion, particularly among those who regularly cooperate, suggesting that call diversification has been favoured by the demands of cooperative activities.
[ "Environmental Biology, Ecology and Evolution", "The Human Mind and Its Complexity" ]
W942039313
Preparation of poly(aryl ether ketone ketone)–silica composite aerogel for thermal insulation application
In this study, poly(aryl ether ketone ketone) (PEKK) with trimethoxysilane pendant groups was prepared first and then chemically cross-linked PEKK–silica composite wet gel was formed through the hydrolysis and condensation reactions of the trimethoxysilane pendant groups at room temperature. 29Si solid-state nuclear magnetic resonance indicated that 70.5 % of the methoxy groups on silicon participated in the condensation reaction. The formed PEKK–silica composite wet gel was dried by freeze-drying from tert-butanol to obtain PEKK–silica composite aerogel, which consisted of polymer fibers tangled together. By adjusting the concentration of PEKK with trimethoxysilane pendant groups in solution, PEKK–silica composite aerogels with different densities (ranging from 0.17 to 0.40 g/cm3) were obtained. The resulting aerogels had small average pore diameters (ranging from 25.0 to 59.4 nm), high surface areas (ranging from 299 to 354 m2/g), low thermal conductivities (ranging from 0.024 to 0.035 W/m K at room temperature) and good mechanical property. Although PEKK lost crystallization ability after incorporating trimethoxysilane pendant groups, the cross-linked PEKK still had a storage modulus as high as 1026 MPa at 300 °C. So, even after being heated at 250 °C for 30 min in air, the pore structure of PEKK–silica composite aerogel was still intact.
[ "Materials Engineering", "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
10.1111/eva.12221
Evolutionary rescue: Linking theory for conservation and medicine
Evolutionary responses that rescue populations from extinction when drastic environmental changes occur can be friend or foe. The field of conservation biology is concerned with the survival of species in deteriorating global habitats. In medicine, in contrast, infected patients are treated with chemotherapeutic interventions, but drug resistance can compromise eradication of pathogens. These contrasting biological systems and goals have created two quite separate research communities, despite addressing the same central question of whether populations will decline to extinction or be rescued through evolution. We argue that closer integration of the two fields, especially of theoretical understanding, would yield new insights and accelerate progress on these applied problems. Here, we overview and link mathematical modelling approaches in these fields, suggest specific areas with potential for fruitful exchange, and discuss common ideas and issues for empirical testing and prediction.
[ "Environmental Biology, Ecology and Evolution", "Prevention, Diagnosis and Treatment of Human Diseases", "Mathematics" ]
10.1109/ICTON.2016.7550517
A Quick View On Current Techniques And Machine Learning Algorithms For Big Data Analytics
Big-data is an excellent source of knowledge and information from our systems and clients, but dealing with such amount of data requires automation, and this brings us to data mining and machine learning techniques. In the ICT sector, as in many other sectors of research and industry, platforms and tools are being served and developed in order to help professionals to treat their data and learn from it automatically; most of those platforms coming from big companies like Google or Microsoft, or from incubators at the Apache Foundation. This brief review explains the basics of machine learning with some ICT examples, and enumerates some (but not all) of the most used tools for analyzing and modelling big-data.
[ "Computer Science and Informatics" ]
EP 9909541 W
METHOD FOR PRODUCING A FLAT STRIP
The invention relates to a method for producing a flat strip in which a supporting fiber fabric comprised of a multitude of parallelly aligned supporting fibers that are interwoven with cross fibers is embedded in a binder matrix made of synthetic material. According to the invention, the supporting fiber fabric (38) is stiffened using a binder matrix made of thermoplastic material and is sealed against liquid penetration. In order to form the binder matrix, the supporting fiber fabric (38) can be pressed together with a film (40', 40'') made of thermoplastic material, heated and cooled again. In an alternative embodiment, the supporting fiber fabric (38) is firstly impregnated with a preferably aqueous thermoplastic suspension (52) and is subsequently heated while vaporizing the water and melting the thermoplastic material and is cooled again while forming the solidified binder matrix.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1534/genetics.119.302045
Early Sex-Chromosome Evolution in the Diploid Dioecious Plant Mercurialis annua
Suppressed recombination allows divergence between homologous sex chromosomes and the functionality of their genes. Here, we reveal patterns of the earliest stages of sex-chromosome evolution in the diploid dioecious herb Mercurialis annua on the basis of cytological analysis, de novo genome assembly and annotation, genetic mapping, exome resequencing of natural populations, and transcriptome analysis. The genome assembly contained 34,105 expressed genes, of which 10,076 were assigned to linkage groups. Genetic mapping and exome resequencing of individuals across the species range both identified the largest linkage group, LG1, as the sex chromosome. Although the sex chromosomes of M. annua are karyotypically homomorphic, we estimate that about one-third of the Y chromosome, containing 568 transcripts and spanning 22. 3 cM in the corresponding female map, has ceased recombining. Nevertheless, we found limited evidence for Y-chromosome degeneration in terms of gene loss and pseudogenization, and most X- and Y-linked genes appear to have diverged in the period subsequent to speciation between M. annua and its sister species M. huetii, which shares the same sex-determining region. Taken together, our results suggest that the M. annua Y chromosome has at least two evolutionary strata: a small old stratum shared with M. huetii, and a more recent larger stratum that is probably unique to M. annua and that stopped recombining ∼1 MYA. Patterns of gene expression within the nonrecombining region are consistent with the idea that sexually antagonistic selection may have played a role in favoring suppressed recombination.
[ "Integrative Biology: from Genes and Genomes to Systems", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
2719851
Establishing in-depth services enhancing the innovation management capacity of south west of france smes in 2020-2021
Raising the competitiveness of SMEs from South West France by offering services linked to innovation management. The project involves 3 partners of the Enterprise Europe Network South West France consortium which covers the region Nouvelle-Aquitaine and the Midi-Pyrénées territory. The general objective is to contribute to raise the competitiveness of SMEs from this area by offering support services in the area of innovation management. The project will also contribute to develop more efficient and more effective innovation processes and higher quality innovation management capacity assessment and support services. The support will be delivered as service packages to 2 groups of SMEs: a) Beneficiaries of the Horizon 2020 SME Instrument phase 2, Fast Track to Innovation and Future Emerging Technologies Open: to enhance the probability of a successful exploitation of the innovation project results and lead to the sustainable growth of the beneficiary beyond the participation in Horizon 2020. The support service will pinpoint weaknesses in the innovation capacities of the beneficiary, select suitable coaches to address the identified weaknesses and monitor the coach-client relationship and to accompany the beneficiary through their European project. b) SMEs with significant innovation activities and a high potential for internationalisation: to enhance their innovation management capacities to be able to gain new international markets and leaderships. The support service will consist in an in-depth innovation assessment in order to develop and implement a tailored action plan to improve the SMEs capacity to manage innovation processes. The partners will use dedicated assessment tools: IMP3rove, Check’Innov, Innovation Way and CCI MAP. The project will last 24 months and will provide 109 support service packages.
[ "Individuals, Markets and Organisations", "Products and Processes Engineering" ]
10.1109/TMTT.2014.2337287
Tunable Bandpass Filter With Two Adjustable Transmission Poles And Compensable Coupling
In this paper, tunable microstrip bandpass filters with two adjustable transmission poles and compensable coupling are proposed. The fundamental structure is based on a half-wavelength (λ/2) resonator with a center-tapped open-stub. Microwave varactors placed at various internal nodes separately adjust the filter's center frequency and bandwidth over a wide tuning range. The constant absolute bandwidth is achieved at different center frequencies by maintaining the distance between the in-band transmission poles. Meanwhile, the coupling strength could be compensable by tuning varactors that are side and embedding loaded in the parallel coupled microstrip lines (PCMLs). As a demonstrator, a second-order filter with seven tuning varactors is implemented and verified. A frequency range of 0. 58-0. 91 GHz with a 1-dB bandwidth tuning from 115 to 315 MHz (i. e. , 12. 6%-54. 3% fractional bandwidth) is demonstrated. Specifically, the return loss of passbands with different operating center frequencies can be achieved with same level, i. e. , about 13. 1 and 11. 6 dB for narrow and wide passband responses, respectively. To further verify the etch-tolerance characteristics of the proposed prototype filter, another second-order filter with nine tuning varactors is proposed and fabricated. The measured results exhibit that the tunable fitler with the embedded varactor-loaded PCML has less sensitivity to fabrication tolerances. Meanwhile, the passband return loss can be achieved with same level of 20 dB for narrow and wide passband responses, respectively.
[ "Systems and Communication Engineering", "Materials Engineering" ]
10.1002/ajpa.22938
Inner ear morphology of the cioclovina early modern European calvaria from Romania
Objectives The morphology of the human bony labyrinth is thought to preserve a strong phylogenetic signal and to be minimally, if at all, affected by postnatal processes. The form of the semicircular canals is considered a derived feature of Neanderthals and different from the modern human anatomy. Among other hominins, European Middle Pleistocene humans have been found to be most similar to Neanderthals. Early modern humans have been proposed to show a pattern that is distinct, but most similar to that of Holocene people. Here we examine the inner ear structures of the Cioclovina calvaria, one of the earliest reliably dated and relatively complete modern human crania from Europe, in the context of recent and fossil human variation. Materials and Methods Bony labyrinths were virtually extracted from CT scans of recent Europeans and Cioclovina. Using univariate and multivariate methods, measurements of the semicircular canals were compared with published measurements of other fossil specimens. Results Our results show that Cioclovina's inner ear morphology falls within the range of modern variation, with affinities to both Late Pleistocene modern humans and recent Europeans. Using discriminant functions, the sex of the Cioclovina specimen is estimated as male. Discussion Results agree with previous work showing that Cioclovina exhibits fully modern cranial morphology.
[ "The Study of the Human Past", "Environmental Biology, Ecology and Evolution" ]
10.1093/brain/awx095
Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia
Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in 3. 1% of index cases. Interestingly, 480% of POLR3A mutation carriers presented the same deep-intronic mutation (c. 1909 + 22G4A), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct and uniform phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c. 1909 + 22G4A demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. The associated c. 1909 + 22G4A variant was significantly enriched in 1139 cases with spastic ataxia-related phenotypes as compared to unrelated neurological and non-neurological phenotypes and healthy controls (P = 1. 3 104). In this study we demonstrate that (i) autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; and (ii) hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Furthermore, our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Neuroscience and Disorders of the Nervous System", "Integrative Biology: from Genes and Genomes to Systems" ]
interreg_3829
Urban Soil Management Strategy
Central Europe is characterised by a relatively high population density. In some of the countries a quarter of the total national population lives in the capital agglomeration, in the other countries urban networks of larger towns exist. These urban areas have a high economic potential, but they are facing a concentration of environmental, social and economic problems often triggered by increasing suburbanisation. Suburbanisation causes significant land consumption and soil sealing. As a natural resource, soil fulfils important ecological functions as well as provides essential services like water filtering and storage, biomass and food production, source of raw material, living space for humans, plants and animals. Therefore the management of this resource has a strong influence on the preservation of nature, but also on the socio-economic development. In particular the flood plains in the area are under high pressure of urbanisation. Land use changes and loss of soil functions impairing environmental quality in urban areas are among environmental risks which are yet not adequately addressed. In most cities across Central Europe there is a considerable amount of data available on soil quality and its different functions. However, to date there is no common urban planning strategy addressing the need for the protection of soil habitat as a critical element controlling urban ecosystem functions. Massive scale consumption of valuable soils by urban fabric leads to the dramatic loss of biodiversity, retention and buffering functions and overall quality of life of urban population. There is an urgent need to develop an urban soil management system accompanied by decision support tools for scenario analysis and assessment of impacts of different planning options on soils. Today there is still very little public awareness of soil issues as a key element of urban ecosystem. Missing awareness due to a low degree of knowledge about the functional role of soils has been identified as main reason for the lacking consideration of soil related aspects in urban planning so far. Therefore raising public as well as political awareness and creating acceptance is a key issue throughout the whole duration of the project. This will be reached by visualisation of the consequences and future problems created by not considering soil related aspects in urban planning process. Overall the project is focusing on the optimisation of land use in urban areas by preserving the natural assets of the resource soil without hindering economic development.
[ "Earth System Science", "Human Mobility, Environment, and Space", "Environmental Biology, Ecology and Evolution" ]
10.1007/JHEP03(2017)132
Two Dimensional Gauge Dynamics And The Topology Of Singular Determinantal Varieties
We record an observation about the Witten indices in two families of gauged linear sigma models: the U(2) model for linear sections of Grassmannians, and the U(1) model for quadric complete intersections. We describe how the Witten indices are related to the Euler characteristics of the singular skew-symmetric or symmetric determinantal varieties featuring in the analysis of their opposite phases, and we discuss the extent to which these relationships can be reconciled with standard Born-Oppenheimer arguments.
[ "Mathematics" ]
10.15252/embj.201490467
Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells
Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli, and this protects long-lived organisms from cancer development. How cells discriminate physiological from supraphysiological levels of Myc is largely unknown. Here, we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-Sequencing experiments show that high levels of Myc invade target sites that lack consensus E-boxes in a complex with Miz1 and repress transcription. Myc/Miz1-repressed genes encode proteins involved in cell adhesion and migration and include several integrins. Promoters of repressed genes are enriched for binding sites of the serum-response factor (SRF). Restoring SRF activity antagonizes Myc repression of SRF target genes, attenuates Myc-induced apoptosis, and reverts a Myc-dependent decrease in Akt phosphorylation and activity, a well-characterized suppressor of Myc-induced apoptosis. We propose that high levels of Myc engage Miz1 in repressive DNA binding complexes and suppress an SRF-dependent transcriptional program that supports survival of epithelial cells. Synopsis Myc-driven apoptosis is a tumor-suppressive mechanism that depends on Myc-mediated repression of cell adhesion proteins and Akt signaling in epithelial cells. Induction of apoptosis by Myc in epithelial cells requires association with Miz1. Myc and Miz1 broadly repress genes involved in cell adhesion and migration. Multiple Myc/Miz1-repressed genes are targets of serum-response factor (SRF). Elevating SRF activity alleviates Myc/Miz1-mediated repression and apoptosis. Myc/Miz1 and SRF have antagonistic effects on Akt activity. Oncogenic levels of Myc promote apoptosis by repressing cell adhesion molecules and Akt signaling in epithelial cells, counteracting serum-response factor activity.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1371/journal.ppat.1002792
Hyperthermia stimulates HIV-1 replication
HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39. 5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39. 5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1109/ITSC.2017.8317634
Structural Observability Of Multi Lane Traffic With Connected Vehicles
We establish sufficient and necessary conditions for the (weak) structural observability as well as the strong structural observability of lane-based highway traffic. Based on these results, we characterize the fixed detector configurations that guarantee the proper operation of a proposed traffic state estimation scheme. The structural observability analyses are based on a data-driven model, which is introduced for the per-lane traffic density dynamics. The proposed model is derived from the well-known conservation law equation via utilization of position and speed information from connected vehicle reports.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1103/PhysRevB.95.195142
Low-energy electronic excitations and band-gap renormalization in CuO
Combining nonresonant inelastic x-ray scattering experiments with state-of-the-art ab initio many-body calculations, we investigate the electronic screening mechanisms in strongly correlated CuO in a large range of energy and momentum transfers. The excellent agreement between theory and experiment, including the low-energy charge excitations, allows us to use the calculated dynamical screening as a safe building block for many-body perturbation theory and to elucidate the crucial role played by d-d excitations in renormalizing the band gap of CuO. In this way we can dissect the contributions of different excitations to the electronic self-energy which is illuminating concerning both the general theory and this prototypical material.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1007/978-3-642-39799-8_11
Automatic Linearizability Proofs Of Concurrent Objects With Cooperating Updates
An execution containing operations performing queries or updating a concurrent object is linearizable w. r. t an abstract implementation (called specification) iff for each operation, one can associate a point in time, called linearization point, such that the execution of the operations in the order of their linearization points can be reproduced by the specification. Finding linearization points is particularly difficult when they do not belong to the operations's actions. This paper addresses this challenge by introducing a new technique for rewriting the implementation of the concurrent object and its specification such that the new implementation preserves all executions of the original one, and its linearizability (w. r. t. the new specification) implies the linearizability of the original implementation (w. r. t. the original specification). The rewriting introduces additional combined methods to obtain a library with a simpler linearizability proof, i. e. , a library whose operations contain their linearization points. We have implemented this technique in a prototype, which has been successfully applied to examples beyond the reach of current techniques, e. g. , Stack Elimination and Fetch&Add.
[ "Computer Science and Informatics" ]
10.1016/j.laa.2012.04.043
Polynomials with and without determinantal representations
The problem of writing real zero polynomials as determinants of linear matrix polynomials has recently attracted a lot of attention. Helton and Vinnikov [9] have proved that any real zero polynomial in two variables has a determinantal representation. Brändén [2] has shown that the result does not extend to arbitrary numbers of variables, disproving the generalized Lax conjecture. We prove that in fact almost no real zero polynomial admits a determinantal representation; there are dimensional differences between the two sets. The result follows from a general upper bound on the size of linear matrix polynomials. We then provide a large class of surprisingly simple explicit real zero polynomials that do not have a determinantal representation. We finally characterize polynomials of which some power has a determinantal representation, in terms of an algebra with involution having a finite dimensional representation. We use the characterization to prove that any quadratic real zero polynomial has a determinantal representation, after taking a high enough power. Taking powers is thereby really necessary in general. The representations emerge explicitly, and we characterize them up to unitary equivalence.
[ "Mathematics" ]
616827
Biophysical networks underlying the robustness of neuronal excitability
The mammalian nervous system is in some respect surprisingly robust to perturbations, as suggested by the virtually complete recovery of brain function after strokes or the pre-clinical asymptomatic phase of Parkinson’s disease. Ultimately though, cognitive and behavioral robustness relies on the ability of single neurons to cope with perturbations, and in particular to maintain a constant and reliable transfer of information. So far, the main facet of robustness that has been studied at the neuronal level is homeostatic plasticity of electrical activity, which refers to the ability of neurons to stabilize their activity level in response to external perturbations. But neurons are also able to maintain their function when one of the major ion channels underlying their activity is deleted or mutated: the number of ion channel subtypes expressed by most excitable cells by far exceeds the minimal number of components necessary to achieve function, offering great potential for compensation when one of the channel’s function is altered. How ion channels are dynamically co-regulated to maintain the appropriate pattern of activity has yet to be determined. In the current project, we will develop a systems-level approach to robustness of neuronal activity based on the combination of electrophysiology, microfluidic single-cell qPCR and computational modeling. We propose to i) characterize the electrical phenotype of dopaminergic neurons following different types of perturbations (ion channel KO, chronic pharmacological treatment), ii) measure the quantitatives changes in ion channel transcriptome (40 voltage-dependent ion channels) associated with these perturbations and iii) determine the mathematical relationships between quantitative changes in ion channel expression and electrical phenotype. Although focused on dopaminergic neurons, this project will provide a general framework that could be applied to any type of excitable cell to decipher its code of robustness.
[ "Neuroscience and Disorders of the Nervous System", "Integrative Biology: from Genes and Genomes to Systems", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2137392540
An evidence-based mobile decision support system for subaxial cervical spine injury treatment
Bringing evidence to practice is a key issue in modern medicine. The key barrier to information searching is time. Clinical decision support systems (CDSS) can improve guideline adherence. Mounting evidence exists that mobile CDSS on handheld computers support physicians in delivering appropriate care to their patients. Subaxial cervical spine injuries account for almost half of spine injuries, and a majority of spinal cord injuries. A valid and reliable classification exists, including evidence-based treatment algorithms. A mobile CDSS on this topic was not yet available. We developed and tested an iPhone application based on the Subaxial Injury Classification (SLIC) and 5 evidence-based treatment algorithms for the surgical approach to subaxial cervical spine injuries. The application can be downloaded for free. Users are cordially invited to provide feedback in order to direct further development and evaluation of CDSS for traumatic lesions of the spinal column.
[ "Computer Science and Informatics", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1364/OE.23.028491
High Intracavity Power Thin Disk Laser For The Alignment Of Molecules
We propose a novel approach for strong alignment of gas-phase molecules for experiments at arbitrary repetition rates. A high-intracavity-power continuous-wave laser will provide the necessary ac electric field of 1010–1011 W/cm2. We demonstrate thin-disk lasers based on Yb:YAG and Yb:Lu2O3 in a linear high-finesse resonator providing intracavity power levels in excess of 100 kW at pump power levels on the order of 50 W. The multi-longitudinal-mode operation of this laser avoids spatial-hole burning even in a linear standing-wave resonator. The system will be scaled up as in-vacuum system to allow for the generation of fields of 1011 W/cm2. This system will be directly applicable for experiments at modern X-ray light sources, such as synchrotrons or free-electron lasers, which operate at various very high repetition rates. This would allow to record molecular movies through temporally resolved diffractive imaging of fixed-in-space molecules, as well as the spectroscopic investigation of combined X-ray–NIR strong-field effects of atomic and molecular systems.
[ "Physical and Analytical Chemical Sciences", "Fundamental Constituents of Matter" ]
W2805733881
Methane Production by Co-Digesting Vinasse and Whey in an AnSBBR: Effect of Mixture Ratio and Feed Strategy
The most common approach to deal with vinasse (sugarcane stillage) is fertigation, but this technique compromises soil structure and surrounding water bodies. A possible solution is to transport vinasse to local cheese whey producers and perform the co-digestion of these wastewaters together, reducing their organic load and generating bioenergy. Therefore, this study investigated the application of an AnSBBR (anaerobic sequencing batch biofilm reactor) operated in batch and fed-batch mode, co-digesting vinasse and whey at 30 °C. The effect of influent composition and feeding strategy was assessed. In all conditions, the system achieved high organic matter removal (approximately 83%). Increasing the percentage of vinasse from 0 to 100% in the influent resulted in a decrease in methane productivity (76.3 to 51.1 molCH4 m-3 day-1) and yield (12.7 to 9.1 molCH4 kgCOD-1), but fed-batch mode operation improved reactor performance (73.0 molCH4 m-3 day-1 and 11.5 molCH4 kgCOD-1). From the kinetic metabolic model, it was possible to infer that, at the best condition, methane is produced in a similar way from the acetoclastic and hydrogenotrophic routes. A scheme of four parallel reactors with a volume of 16,950 m3 each was proposed in the scale-up estimation, with an energy recovery estimated in 28,745 MWh per month.
[ "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution" ]
216407
Exercise as a regulator of hepatic nad metabolism and mitochondrial function in non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in industrialized countries, including Europe, and comprises a spectrum of disorders ranging from hepatic lipid accumulation (steatosis) to inflammation (non-alcoholic steatohepatitis, NASH) and fibrosis. Pathogenic pathways leading from hepatic steatosis to NASH are still incompletely understood resulting in a lack of approved therapeutic options besides life style changes. Physical activity is effective to prevent NAFLD progression. The mechanism of exercise action on liver mitochondrial metabolism is not clear yet. However, exercise might exert its positive effects via increasing hepatic nicotinamide adenine dinucleotide (NAD) levels. Several studies showed that the hepatic NAD metabolism is dysregulated during the development of NAFLD and that exercise has a positive effect on NAD metabolism and function of NAD dependent enzymes in skeletal muscle. The functionality of mitochondrial metabolism is highly dependent on the maintenance of the organellar NAD pool. Mitochondrial dysfunction has been implicated in the progression from steatosis to NASH. We hypothesize that a dysregulated NAD metabolism in the liver is involved in the development of hepatic mitochondrial dysfunction in NAFLD/NASH. Our overall aim is to define the impact of exercise on hepatic mitochondrial dysfunction and test whether exercise effects are mediated via restoration of NAD metabolism. We will achieve this by combining the knowledge on hepatic NAD metabolism of the fellow with the expertise in exercise mouse models and on analysis of mitochondrial function of the Supervisor. This study is one of the first to comprehensively examine the interaction between exercise, mitochondrial dysfunction as a cause of NAFLD and NAD metabolism specifically in the liver and in hepatocytes and ultimately aims to identify novel therapeutic targets for the prevention and treatment of NAFLD.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1073/pnas.0905394106
Protein contents in biological membranes can explain abnormal solvation of charged and polar residues
Transmembrane helices are generally believed to insert into membranes based on their hydrophobicity. Nevertheless, there are important exceptions where polar residues have great functional importance, for instance the S4 helix of voltage-gated ion channels. It has been shown experimentally that insertion can be accomplished by hydrophobic counterbalance, predicting an arginine insertion cost of only 2. 5 kcal/mol, compared with 14. 9 kcal/mol in cyclohexane. Previous simulations of pure bilayers have produced values close to the pure hydrocarbon, which has lead to spirited discussion about the experimental conditions. Here, we have performed computer simulations of models better mimicking biological membranes by explicitly including protein helices at mass fractions from 15% to 55%, as well as an actual translocon. This has a striking effect on the solvation free energy of arginine. With some polar residues present, the solvation cost comes close to experimental observation at approximately 30% mass fraction, and negligible at 40%. In the presence of a translocon in the membrane, the cost of inserting arginine next to the lateral gate can be as low as 3–5 kcal/mol. The effect is mainly due to the extra helices making it easier to retain hydration water. These results offer a possible explanation for the discrepancy between the in vivo hydrophobicity scale and computer simulations and highlight the importance of the high protein contents in membranes. Although many membrane proteins are stable in pure bilayers, such simplified models might not be sufficiently accurate for insertion of polar or charged residues in biological membranes.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
interreg_1931
Spatial aspects of the Information Society
The development of Information and Communication Technologies (ICTs) and the liberalisation of the telecom sector have given a growing number of people the possibility to access to all type of information and also have contributed to promote the communication among citizens, businesses and public administrations, removing the constraints of time, place and distance, making the world a "global village". Therefore, this technological development is a key for the development of a knowledge based economy in which the information can be transmitted and be accessible by all within a "global network" - The Information Society. The general objective of this project is to characterize the information society from a territorial perspective and analyse its territorial aspects at macro, meso and micro level. The project is envisaged to consider both decentralised and centralised territorial effects of the information society at short-term and mid-term/long-term perspective and relate it with the goals and policy options defined in the ESDP. It will also cover rural and peripheral areas of the European Union, where the information society could be an important step towards their development, as well as the role of the information society in the development of urban-rural functional relations. The underlying objective is to assess the possible contribution of the information society to balanced spatial development, territorial cohesion and polycentricity.
[ "Human Mobility, Environment, and Space", "Systems and Communication Engineering" ]
10.1080/17470218.2016.1195851
Event-related potentials reveal the development of stable face representations from natural variability
Natural variability between instances of unfamiliar faces can make it difficult to reconcile two images as the same person. Yet for familiar faces, effortless recognition occurs even with considerable variability between images. To explore how stable face representations develop, we employed incidental learning in the form of a face sorting task. In each trial, multiple images of two facial identities were sorted into two corresponding piles. Following the sort, participants showed evidence of having learnt the faces performing more accurately on a matching task with seen than with unseen identities. Furthermore, ventral temporal event-related potentials were more negative in the N250 time range for previously seen than for previously unseen identities. These effects appear to demonstrate some degree of abstraction, rather than simple picture learning, as the neurophysiological and behavioural effects were observed with novel images of the previously seen identities. The results provide evidence of the development of facial representations, allowing a window onto natural mechanisms of face learning.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity" ]
10.1002/anie.201505179
A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins
A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformation-switching stem-loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (<10 min) and selectively, enabling the facile detection of specific proteins even in complex samples, such as blood serum. The versatility of the platform was demonstrated by detecting five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) with low nanomolar detection limits and no detectable cross-reactivity.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
US 36256182 A
Leg stretching apparatus
Disclosed are two separate leg supporting members which are independently pivotally connected to a base assembly. At their pivotal connection with the base assembly they are further provided with a disk assembly having a cable attached thereto. The cable from each leg supporting member is attached through guide means to a crank assembly which, during operation, forces the leg supporting members apart stretching the legs of a user of a device into a "split" position. The crank assembly housing is pivotally mounted such that when the housing is moved forward and/or rearward, the cable path of both cables is lengthened a small amount, providing the user with a controlled minute additional stretching movement. The leg supporting members during non-use are retractable partially into the base assembly and a torso retaining seat back assembly can be folded flat. The crank housing assembly can also be folded down on top of the seat back assembly providing a very compact storage configuration. In a preferred embodiment, a friction brake device is affixed to the crank assembly such that the user can straighten his legs away from the "split" position, thus strengthening his leg muscles as well as stretching them.
[ "Products and Processes Engineering" ]
10.1016/j.pbi.2016.06.009
Leaf growth in dicots and monocots: So different yet so alike
In plants, most organs grow post-embryonically through cell division and cell expansion. The coordination of these two growth processes is generally considered to be different between dicots and monocots. In dicot plants, such as the model plant Arabidopsis, leaf growth is most often described as being temporally regulated with cell division ceasing earlier at the tip and continuing longer at the base of the leaf. Conversely, in monocot leaves, the organization of the growth processes is rather viewed as spatially regulated with dividing cells at the base of the leaf, followed by expanding cells and finally mature cells at the tip. As our understanding of the leaf growth processes in the two major classes of flowering plants expands, it becomes increasingly clear that the regulation of the growth processes is to a great extent conserved between dicots and monocots. In this review, we highlight how the temporal and spatial organization of cell division and cell expansion takes place in both dicot and monocot leaves. We also show that there are similarities in the molecular wiring that coordinates these two processes during leaf development.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2157734648
SUSCEPTIBILITY OF POTATO TUBER MOTH, PHTHORIMAEA OPERCULELLA (ZELLER) TO CIPC (CHLORPROPHAM)
CIPC is normally used for sprout inhibition in stored potatoes meant for processing and table purposes. This compound has been tested as a substitute for chemical pesticides in integrated management of phthorimaea operculella in potato stores. The effect of cipc against different stages of p. operculella was evaluated through bioassays. The relative susceptibility of various stages of p. operculella was studied by topical application in the laboratory at 26°c incubation. LC 50 of CIPC to eggs was 0.0359%. The susceptibility of CIPC decreased with increasing larval age. The LC 50 increased from 0.0398% for neonate larvae to 0.0487%, 0.0512%and 0.0795% for second, third and fourth instar larvae, respectively. pupa was found more susceptible as compared to fourth instar larvae with LC 50 of 0.0500%. CIPC was found highly effective against p. operculella adults. There was 100.0% mortality of adults released on CIPC (0.06%) treated tubers in glass jars. The persistence studies revealed 25% mortality of adults after 7 days of treatment. after two months of storage, there was no potato tuber moth infestation in tubers treated with CIPC (0.06%) as compared to 84% in control. CIPC completely stopped the development of sprouts up to a period of two months. with larvae already in tubers, the cipc was extremely effective, with a success rate of 100%. These results indicated good prospects of CIPC application for management of potato tuber moth in country stores.
[ "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution" ]
10.1002/glia.22737
Adapting brain metabolism to myelination and long-range signal transduction
In the mammalian brain, the subcortical white matter comprises long-range axonal projections and their associated glial cells. Here, astrocytes and oligodendrocytes serve specific functions during development and throughout adult life, when they meet the metabolic needs of long fiber tracts. Within a short period of time, oligodendrocytes generate large amount of lipids, such as cholesterol, and membrane proteins for building the myelin sheaths. After myelination has been completed, a remaining function of glial metabolism is the energetic support of axonal transport and impulse propagation. Astrocytes can support axonal energy metabolism under low glucose conditions by the degradation of stored glycogen. Recently it has been recognized that the ability of glycolytic oligodendrocytes to deliver pyruvate and lactate is critical for axonal functions in vivo. In this review, we discuss the specific demands of oligodendrocytes during myelination and potential routes of metabolites between glial cells and myelinated axons. As examples, four specific metabolites are highlighted (cholesterol, glycogen, lactate, and N-acetyl-aspartate) that contribute to the specific functions of white matter glia. Regulatory processes are discussed that could be involved in coordinating metabolic adaptations and in providing feedback information about metabolic states.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1109/TWC.2015.2443044
Joint Precoding And Load Balancing Optimization For Energy Efficient Heterogeneous Networks
This paper considers a downlink heterogeneous network, where different types of multiantenna base stations (BSs) communicate with a number of single-antenna users. Multiple BSs can serve the users by spatial multiflow transmission techniques. Assuming imperfect channel state information at both BSs and users, the precoding, load balancing, and BS operation mode are jointly optimized for improving the network energy efficiency. We minimize the weighted total power consumption while satisfying quality-of-service constraints at the users. This problem is nonconvex, but we prove that for each BS mode combination, the considered problem has a hidden convexity structure. Thus, the optimal solution is obtained by an exhaustive search over all possible BS mode combinations. Furthermore, by iterative convex approximations of the nonconvex objective function, a heuristic algorithm is proposed to obtain a suboptimal solution of low complexity. We show that although multicell joint transmission is allowed, in most cases, it is optimal for each user to be served by a single BS. The optimal BS association condition is parameterized, which reveals how it is impacted by different system parameters. Simulation results indicate that putting a BS into sleep mode by proper load balancing is an important solution for energy savings.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1051/0004-6361/201628306
Empirical Mode Decomposition Analysis Of Random Processes In The Solar Atmosphere
Context. Coloured noisy components with a power law spectral energy distribution are often shown to appear in solar signals of various types. Such a frequency-dependent noise may indicate the operation of various randomly distributed dynamical processes in the solar atmosphere. Aims. We develop a recipe for the correct usage of the empirical mode decomposition (EMD) technique in the presence of coloured noise, allowing for clear distinguishing between quasi-periodic oscillatory phenomena in the solar atmosphere and superimposed random background processes. For illustration, we statistically investigate extreme ultraviolet (EUV) emission intensity variations observed with SDO/AIA in the coronal (171 A), chromospheric (304 A), and upper photospheric (1600 A) layers of the solar atmosphere, from a quiet sun and a sunspot umbrae region. Methods. EMD has been used for analysis because of its adaptive nature and essential applicability to the processing non-stationary and amplitude-modulated time series. For the comparison of the results obtained with EMD, we use the Fourier transform technique as an etalon. Results. We empirically revealed statistical properties of synthetic coloured noises in EMD, and suggested a scheme that allows for the detection of noisy components among the intrinsic modes obtained with EMD in real signals. Application of the method to the solar EUV signals showed that they indeed behave randomly and could be represented as a combination of different coloured noises characterised by a specific value of the power law indices in their spectral energy distributions. On the other hand, 3-min oscillations in the analysed sunspot were detected to have energies significantly above the corresponding noise level. Conclusions. The correct accounting for the background frequency-dependent random processes is essential when using EMD for analysis of oscillations in the solar atmosphere. For the quiet sun region the power law index was found to increase with height above the photosphere, indicating that the higher frequency processes are trapped deeper in the quiet sun atmosphere. In contrast, lower levels of the sunspot umbrae were found to be characterised by higher values of the power law index, meaning the domination of lower frequencies deep inside the sunspot atmosphere. Comparison of the EMD results with those obtained with the Fourier transform showed good consistency, justifying the applicability of EMD.
[ "Physical and Analytical Chemical Sciences", "Universe Sciences" ]
10.1051/0004-6361/201322066
Variation In Dust Properties In A Dense Filament Of The Taurus Molecular Complex L1506
We observed the L1506 filament, which is located in the Taurus molecular complex, with the Herschel PACS and SPIRE instruments. Our aim is to prove the variation in grain properties along the entire length of the filament. In particular, we want to determine above which gas density this variation arises and what changes in the grain optical properties/size distribution are required. We use the 3D radiative transfer code CRT, coupled to the dust emission and extinction code DustEM, to model the emission and extinction of the dense filament. We test a range of optical properties and size distributions for the grains: dust of the diffuse interstellar medium (interstellar PAHs and amorphous carbons and silicates) and both compact and fluffy aggregates. We find that the grain opacity has to increase across the filament to fit simultaneously the near-IR extinction and Herschel emission profiles of L1506. We interpret this change to be a consequence of the coagulation of dust grains to form fluffy aggregates. Grains similar to those in the diffuse medium have to be present in the outer layers of the cloud, whereas aggregates must prevail above gas densities of a few 1000 H/cm3. This corresponds to line-of-sights with visual extinction in the V band of the order of 2 to 3. The dust opacity at 250 microns is raised by a factor of 1. 8 to 2. 2, while the grain average size is increased by a factor of 5. These exact numbers depend naturally on the dust model chosen to fit the data. Our findings agree with the constraints given by the study of the gas molecular lines. Using a simple approach, we show that the aggregates may have time to form inside the filament within the cloud lifetime. Our model also characterises the density structure of the filament, showing that the filament width is not constant along L1506 but instead varies by a factor of the order of 4.
[ "Physical and Analytical Chemical Sciences", "Universe Sciences" ]
W2137672931
Utility Mining Algorithm for High Utility Item sets from Transactional Databases
The discovery of item sets with high utility like profits is referred by mining high utility item sets from a transactional database. Although in recent years a number of relevant algorithms have been proposed, for high utility item sets the problem of producing a large number of candidate item sets is incurred. The mining performance is degraded by such a large number of candidate item sets in terms of execution time and space requirement. When the database contains lots of long transactions or long high utility item sets the situation may become worse. Internet purchasing and transactions is increased in recent years, mining of high utility item sets especially from the big transactional databases is required task to process many day to day operations in quick time. There are many methods presented for mining the high utility item sets from large transactional datasets are subjected to some serious limitations such as performance of this methods needs to be investigated in low memory based systems for mining high utility itemsets from large transactional datasets and hence needs to address further as well. Another limitation is these proposed methods cannot overcome the screenings as well as overhead of null transactions; hence, performance degrades drastically. During this paper, we are presenting the new approach to overcome these limitations. We presented distributed programming model for mining business-oriented transactional datasets by using an improved Map Reduce framework on Hadoop, which overcomes not only the single processor and main memory-based computing, but also highly scalable in terms of increasing database size. We have used this approach with existing UP-Growth and UP-Growth+ with aim of improving their performances further. In experimental studies we will compare the performances of existing algorithms UP-Growth and UP-Growth+ against the improve UP-Growth and UP-Growth+ with Hadoop.
[ "Computer Science and Informatics" ]
interreg_3585
TEMPTING STREETS
The general objective of the project is the realisation of an integrated commercial agri-food and tourist system, capable of strengthening the competitiveness of local SMEs. The main outputs include: • Identification of high quality agri-food products such as olive-oil, wine, dairy etc. (De.Co.), through an analysis of the target territories • Realization of a web portal as a Knowledge Base, favoring the informal connection between enterprises and professional organizations. • Organization of events aiming at the sharing and exchange of local products – 2 fairs in Greece and Italy under the theme “Strade Golose” . • On-line training courses for new professionals in the agri-food sector. • Planning and implementation of “didactic-tourist packages” and virtual educational tours in the typical areas of production (wine factories, oil mills)
[ "Individuals, Markets and Organisations", "Human Mobility, Environment, and Space" ]
10.1128/aem.01832-18
Response of the Anaerobic Methanotroph “ Candidatus Methanoperedens nitroreducens” to Oxygen Stress
“ Candidatus Methanoperedens nitroreducens” is an anaerobic archaeon which couples the reduction of nitrate to the oxidation of methane. This microorganism is present in a wide range of aquatic environments and man-made ecosystems, such as paddy fields and wastewater treatment systems. In such environments, these archaea may experience regular oxygen exposure. However, “ Ca . Methanoperedens nitroreducens” is able to thrive under such conditions and could be applied for the simultaneous removal of dissolved methane and nitrogenous pollutants in oxygen-limited systems. To understand what machinery “ Ca . Methanoperedens nitroreducens” possesses to counteract the oxidative stress and survive, we characterized the response to oxygen exposure using a multi-omics approach.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Environmental Biology, Ecology and Evolution" ]
10.1534/g3.113.009142
Yeast Growth Plasticity Is Regulated by Environment-Specific Multi-QTL Interactions
For a unicellular, non-motile organism like Saccharomyces cerevisiae, carbon sources act both as nutrients and as signaling molecules and consequently affect various fitness parameters including growth. It is therefore advantageous for yeast strains to adapt their growth to carbon source variation. The ability of a given genotype to manifest different phenotypes in varying environments is known as phenotypic plasticity. To identify quantitative trait loci (QTL) that drive plasticity in growth, two growth parameters (growth rate and biomass) were measured in a published dataset from meiotic recombinants of two genetically divergent yeast strains grown in different carbon sources. To identify QTL contributing to plasticity across pairs of environments, gene–environment interaction mapping was performed, which identified several QTL that have a differential effect across environments, some of which act antagonistically across pairs of environments. Multi-QTL analysis identified loci interacting with previously known growth affecting QTL as well as novel two-QTL interactions that affect growth. A QTL that had no significant independent effect was found to alter growth rate and biomass for several carbon sources through two-QTL interactions. Our study demonstrates that environment-specific epistatic interactions contribute to the growth plasticity in yeast. We propose that a targeted scan for epistatic interactions, such as the one described here, can help unravel mechanisms regulating phenotypic plasticity.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
173568
Development of a universal kit to be installed on existing and new high tonnage hot forgingpresses, for a potential strong reduction of energy consumption of the european installed fleet.
FARINA PRESSE, 80 years old Italian SME specialized in High Tonnage Hot Forging Presses (HTHFP: > 25.000 kN) with a solid R&D tradition and a fame of excellence in hot forging sector, aims at developing a UNIVERSAL KIT, suitable to be installed on the most different types of existing HTHFPs, capable to reduce up to 30% their electric energy consumption and increase up to 33% their productivity, so that to address the potential of the European working HTHFPs' fleet and obtain an important energy consumption reduction at system level. The European forging industry, an highly energy intensive sector, is steadly forced to reduce production costs and increase production volumes. The project will allow to meet the forging industry needs and its application on the European market will obtain significant energy saving on European energy networks. We estimate our kit will allow to save about 210 MWh/year for an average HTHFP, actually dissipated as unproductive heat: if extended to the European HTHFP fleet, it means a potential saving of 420 GWh/year, equivalent to a reduction of 210.000 tons CO2 emission per year.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1126/science.1249771
Coherent ultrafast charge transfer in an organic photovoltaic blend
Blends of conjugated polymers and fullerene derivatives are prototype systems for organic photovoltaic devices. The primary charge-generation mechanism involves a light-induced ultrafast electron transfer from the light-absorbing and electron-donating polymer to the fullerene electron acceptor. Here, we elucidate the initial quantum dynamics of this process. Experimentally, we observed coherent vibrational motion of the fullerene moiety after impulsive optical excitation of the polymer donor. Comparison with first-principle theoretical simulations evidences coherent electron transfer between donor and acceptor and oscillations of the transferred charge with a 25-femtosecond period matching that of the observed vibrational modes. Our results show that coherent vibronic coupling between electronic and nuclear degrees of freedom is of key importance in triggering charge delocalization and transfer in a noncovalently bound reference system.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1038/srep41349
How white and black bodies are perceived depends on what emotion is expressed
Body language is a powerful indicator of others' emotions in social interactions, with positive signals triggering approach and negative ones retreat and defensiveness. Intergroup and interracial factors can influence these interactions, sometimes leading to aggressive or even violent behaviour. Despite its obvious social relevance however, the interaction between body expression and race remains unexplored, with explanations of the impact of race being almost exclusively based on the role of race in face recognition. In the current fMRI study we scanned white European participants while they viewed affective (angry and happy) body postures of both same race (white) and other race (black) individuals. To assess the difference between implicit and explicit recognition participants performed either an explicit emotion categorisation task, or an irrelevant shape judgement task. Brain activity was modulated by race in a number of brain regions across both tasks. Race-related activity appeared to be task-as well as emotion-specific. Overall, the other-race effects appeared to be driven by positive emotions, while same-race effects were observed for negative emotions. A race specific effect was also observed in right amygdala reflecting increased activation for explicit recognition of angry white body expressions. Overall, these results provide the first clear evidence that race influences affective body perception.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity", "The Social World and Its Interactions" ]
10.1071/WF16198
Downward Spread Of Smouldering Peat Fire The Role Of Moisture Density And Oxygen Supply
Smouldering fires in peatland are different from the flames in wildland fires. Smouldering peat fire is slow, low-temperature and more persistent, releasing large amounts of smoke into the atmosphere. In this work, we experimentally and computationally investigate the vertical downward spread of smouldering fire in a column of 30cm-tall moss peat under variable moisture content (MC) and bulk density. The measured downward spread rate decreases with depth and wet bulk density, and is ~1cmh−1 equivalent to a carbon emission flux of 200 tonnesday−1ha−1. We observe that downward spread increases as MC increases substantially at least inside the range from 10 to 70%, which is not intuitive and goes against the trend observed for the horizontal spread in the same peat. We also conduct one-dimensional computational simulations to successfully reproduce the experimental observations. The analysis shows that the spread rate increases with MC and decreases with density because smouldering spread is controlled by the oxygen supply. The volume of the porous peat expands when absorbing water, which reduces the density of organic matter and decreases the heat release rate. This shows that the widely assumed conclusion that the spread rate of wildfire decreases with MC is not universal when applied to smouldering fires.
[ "Earth System Science", "Physical and Analytical Chemical Sciences" ]
US 2004/0012797 W
HYDRAULICALLY ACTUATED PUMP FOR LONG DURATION MEDICAMENT ADMINISTRATION
Presently disclosed is a hydraulic pump device and its use thereof, especially in a fluid delivery system. In one embodiment, the fluid delivery system is an inexpensive, single-use device for slow dosing medicament applications. The fluid delivery system may employ a spring-compressed bellows crank or other combination of simple mechanisms operating according to the well-known peristaltic principle to force a volume of ultrapure bio-inert hydraulic fluid through an aperture, thereby expanding one chamber of a two chamber hydraulic cylinder. The second, fluid storage chamber, containing the medicament, is emptied through a conventional orifice in response to the expansion of the pump chamber. The medicament may thence flow through any suitable infusion set into a patient removeably attached thereto.
[ "Products and Processes Engineering", "Materials Engineering" ]
W4210316655
Ética y deberes en los nuevos códigos deontológicos. Una visión desde Italia
De un tiempo a esta parte proliferan una serie de códigos deontológicos ue establecen los deberes y directrices éticos atribuibles al ejercicio de una determinada profesión. Para entender bien este fenóieno es necesario reconstruir el origen y la posterior evolución de la deontología, la naturaleza del ‘deber’ de los códigos deontológicos y la ética profesional, la funcion y calificación de las reglas deontológicas. La naturaleza de las normas deontológicas no ha sido un tema pacífico. Supone volver al debate sobre la relación entre derecho y moral. En el presente artículo se analiza la posición de la jurisprudencia italiana en relación con las propias consideraciones al respecto de esta cuestión que realizan los códigos deontológicos de la abogacía española, de la abogacía italiana, así como el de los abogados europeos.
[ "Texts and Concepts", "Institutions, Governance and Legal Systems" ]
W1805742845
The effect of variable gait modes on walking parameters among children post severe traumatic brain injury and typically developed controls
The goal of the present study was to assess the effect of various walking modes on dynamic gait characteristics and to evaluate the possible differences in the adaptation reactions between children post severe traumatic brain injury (TBI) and typically developed (TD) controls.Thirteen children post severe TBI, mean of 3.5 years post trauma, independent walkers, with a walking velocity > 1.1 m/sec, and 15 TD controls participated in this study. Ages were 7-13 years. Gait speed, step time and length and step time and length variability were assessed by an electronic walkway. The children completed three cycles on the walkway for each of the following situations: comfortable walking, walking as fast as possible, as slow as possible and walking on a straight line.Despite a similar walking performance while walking at a "regular" speed, children post severe TBI exhibit a significantly reduced range of walking speeds (73-154 cm/sec), about half, as compared to TD children (54-193 cm/sec) across the study assignments. In addition, while "walking on a straight line" children post TBI walk slower, with increased step variability as compared to their peers.Children post severe traumatic brain injury may achieve independent walking at a comparable rate to typically developed controls; however their impairments will be exacerbated as the demands increase. Since a variety of walking speeds is crucial for independent daily living at any age and for children in particular, and since adequate balance is an inherent element of walking, these issues need repeated assessments and the children should receive appropriate treatment.
[ "Neuroscience and Disorders of the Nervous System", "Physiology in Health, Disease and Ageing" ]
10.1109/LCOMM.2015.2429574
Single Odsb Radio Over Fiber Signal Supports Stbc At Each Rap
We propose and mathematically characterize a novel radio-over-fiber (ROF) downlink, where a radio access point (RAP) benefits from the transmit diversity gain of space–time block coding (STBC). Significantly, this transmit diversity is achieved using a single optical modulator in the base station (BS). In the proposed architecture, each RAP is fed with a single optical double-sideband signal, where each sideband transmits one of the two STBC-encoded signals. This optical signal is generated in the BS by performing the simultaneous optical upconversion of the baseband STBC signals using a single Mach–Zehnder modulator. The proposed optical backhaul is designed and simulated to impose negligible degradation to that imposed by the dominant wireless link, thereby enabling a designer to exploit the advantages offered by a wireless link having a diversity gain.
[ "Systems and Communication Engineering", "Mathematics" ]
10.1088/0004-637X/762/2/127
New Scaling For The Alpha Effect In Slowly Rotating Turbulence
Using simulations of slowly rotating stratified turbulence, we show that the alpha effect responsible for the generation of astrophysical magnetic fields is proportional to the logarithmic gradient of kinetic energy density rather than that of momentum, as was previously thought. This result is in agreement with a new analytic theory developed in this paper for large Reynolds numbers. Thus, the contribution of density stratification is less important than that of turbulent velocity. The alpha effect and other turbulent transport coefficients are determined by means of the test-field method. In addition to forced turbulence, we also investigate supernova-driven turbulence and stellar convection. In some cases (intermediate rotation rate for forced turbulence, convection with intermediate temperature stratification, and supernova-driven turbulence) we find that the contribution of density stratification might be even less important than suggested by the analytic theory.
[ "Universe Sciences", "Mathematics" ]
10.1103/PhysRevB.82.113104
Generalized gradient approximation bridging the rapidly and slowly varying density regimes: A PBE-like functional for hybrid interfaces
We propose a generalized gradient approximation constructed for hybrid interfaces, which is based on the Perdew, Burke, Ernzerhof (PBE) functional form and interpolates between the rapidly PBE and slowly varying (PBEsol, the revised PBE for solid-state systems) density regimes. This functional approximation (named PBEint) recovers the right second-order gradient expansion of the exchange energy and is accurate for jellium surfaces, interacting jellium slabs, molecules, solids, and metal-molecule interfaces.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1051/0004-6361/201527580
Four And One More The Formation History And Total Mass Of Globular Clusters In The Fornax Dsph
This is the author accepted manuscript. The final version is available from EDP Sciences via http://dx. doi. org/10. 1051/0004-6361/201527580
[ "Universe Sciences" ]
10.1111/1365-2664.12927
Artificial Light At Night Alters Grassland Vegetation Species Composition And Phenology
The research leading to this paper has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 268504 to K. J. G.
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
10.1088/1742-6596/644/1/012025
Morphological And Compositional S Tem Analysis Of Multiple Exciton Generation Solar Cells
Quantum confinement of charge carriers in semiconductor nanocrystals produces optical and electronic properties that have the potential to enhance the power conversion efficiency of solar cells. One of these properties is the efficient formation of more than one electron-hole pair from a single absorbed photon, in a process called multiple exciton generation (MEG). In this work we studied the morphology of nanocrystal multilayers of PbSe treated with CdCl2 using complementary imaging and spectroscopy techniques to characterise the chemical composition and morphology of full MEG devices made with PbSe nanorods (NRs). IN the scanning TEM (STEM), plan view images and chemical maps were obtained of the nanocrystal layers, which allowed for the analysis of crystal structure and orientation, as well as size distribution and aspect ratio. These results were complemented by cross-sectional images of full devices, which allowed accessing the structure of each layer that composes the device, including the nanorod packing in the active nanocrystal layer.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
310884
Towards evidence-based genomic medicine: filling the evidence gaps through modelling studies
At increasingly high rate, genome-wide association and whole genome sequencing studies unravel genetic variants implicated in common diseases such as coronary heart disease, cancer, dementia and type 2 diabetes. One of the major promises is that these advances will lead to more personalized medicine, in which preventive and therapeutic interventions are targeted to individuals based on their genetic profiles. There is increasing interest in the early adoption of novel applications and many commercial applications are already marketed without supporting empirical evidence. Already now, regulatory agencies like the US Food and Drug Administration face substantial gaps in empirical evidence, which hamper proper recommendations. The increasing interest in genomic medicine, the evidence gaps and the scarcity of research budgets are strong incentives to search for novel strategies that make the process of translation research more efficient and effective. This project aims to investigate modelling approaches that can be used to predict the expected outcomes of empirical studies on the basis of published epidemiological and intervention studies. This approach can be used to 1) identify genomic applications that are promising and warrant further empirical research, and 2) fill in evidence gaps by identifying applications that are not expected to improve health or health care. When they are valid, precise and simple, modelling studies can optimize the process of translational research so that time and money are allocated to the most promising applications. In this project, I will 1) characterize empirical studies in translational research in terms of the main outcome measures used and their key determinants; 2) develop simulation models that predict outcome measures; 3) investigate how accuracy and precision of the estimates vary with varying model complexity; and 4). investigate the generalizability of the modelling approaches.
[ "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases", "Computer Science and Informatics" ]
10.1111/apha.12460
Modulation of microRNA-375 expression alters voltage-gated Na<sup>+</sup> channel properties and exocytosis in insulin-secreting cells
MiR-375 has been implicated in insulin secretion and exocytosis through incompletely understood mechanisms. Here we aimed to investigate the role of miR-375 in the regulation of voltage-gated Na+ channel properties and glucose-stimulated insulin secretion in insulin-secreting cells. Methods: MiR-375 was overexpressed using double-stranded mature miR-375 in INS-1 832/13 cells (OE375) or downregulated using locked nucleic acid (LNA)-based anti-miR against miR-375 (LNA375). Insulin secretion was determined using RIA. Exocytosis and ion channel properties were measured using the patch-clamp technique in INS-1 832/13 cells and beta-cells from miR-375KO mice. Gene expression was analysed by RT-qPCR, and protein levels were determined by Western blot. Results: Voltage-gated Na+ channels were found to be regulated by miR-375. In INS-1 832/13 cells, steady-state inactivation of the voltage-gated Na+ channels was shifted by approx. 6 mV to a more negative membrane potential upon down-regulation of miR-375. In the miR-375 KO mouse, voltage-gated Na+ channel inactivation was instead shifted by approx. 14 mV to a more positive membrane potential. Potential targets differed among species and expression of suggested targets Scn3a and Scn3b in INS-1 832/13 cells was only slightly moderated by miR-375. Modulation of miR-375 levels in INS-1-832/13 cells did not significantly affect insulin release. However, Ca2+ dependent exocytosis was significantly reduced in OE375 cells. Conclusion: We conclude that voltage-gated Na+ channels are regulated by miR-375 in insulin-secreting cells, and validate that the exocytotic machinery is controlled by miR-375 also in INS-1 832/13 cells. Altogether we suggest miR-375 to be involved in a complex multifaceted network controlling insulin secretion and its different components.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration" ]
887828
A multi-sided business platform for plug and produce industrial product service systems
The objective of MARKET4.0 is to define, develop and validate an open multi-sided marketplace, based on a trusted P2P data sharing infrastructure for Industry 4.0, that brings together Industrial Product Service Systems (IPSS) providers (supply side) and OEMs as their customers (demand side). It will allow direct interaction among the different sides to improve the sales power of production equipment SMEs. MARKET4.0 will offer advanced web-presence of production equipment SMEs extended by functionalities such as simulations, VR/AR capabilities and a P2P (Industrial Data Space) offering smart user-services and a secure API to try and test the Digital Twin of the production equipment, on top supplier and customer data. This will facilitate direct transactions between market peers (supplier-to-supplier, supplier-to-customer, customer-to-suppliers and more) during the entire B2B lifecycle, i.e. from equipment search to procurement and commissioning. MARKET4.0 will create trust in the business transactions between SME production equipment manufacturers and their customers, as an integral element of the Industrial Data Space (IDS) reference architecture. It includes technological trust (simulation before purchasing), financial trust (Blockchain distributed ledger technology for secure payment), delivery and (anonymized) feedback. In MARKET4.0 the supply side (mainly SMEs) may offer a) production equipment, b) services that extend the capabilities of the production equipment, c) production equipment as a service and d) collaborative engineering services. The marketplace will generate additional value by providing engineering services and acting as a mediator between suppliers and customers.
[ "Products and Processes Engineering", "Computer Science and Informatics", "Systems and Communication Engineering" ]
interreg_2320
Models of Integrated Tourism in the MEDiterranean Plus
MITOMED+ is multi-module project combining Testing and Capitalization (M2+M3). It is a follow up of the previous MITOMED project (MED Maritime), which has been working to promote the integrated management of M&C tourism by improving the knowledge of data, products, services through a set of indicators based on the NECSTouR model. MITOMED+ takes farther these results aiming to improve the coordination of strategies between territories at transnational level regarding the development of the M&C tourism through cooperation and joint planning between regions. _x000D_ The main objective of the project deals with the enhancement of sustainability and responsibility in M&C tourism, by improving local and regional strategies and policy actions and coordinating them at a wider MED transnational level. To achieve this objective, the project intends to increase knowledge and social dialogue regarding the development of a sustainable and responsible M&C tourism in each partner region for better decision-making, improve M&C tourism planning at destination level and its coordination for a transnational governance, mainstream its results into local, regional and national policies and set up a MED M&C tourism management model. The project brings together a right mix of regional authorities and their networks, associations of local authorities, territorial development agencies, higher education institution and research centers, having the appropriate competences and expertise in M&C tourism.
[ "Human Mobility, Environment, and Space", "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
10.1021/acsmacrolett.6b00782
Covalent cross-linking of porous poly(ionic liquid) membrane via a triazine network
Porous poly(ionic liquid) membranes that were prepared via electrostatic cross-linking were subsequently covalently cross-linked via formation of a 1, 3, 5-triazine network. The additional covalent cross-links do not affect pore size and pore size distribution of the membranes and stabilize them toward salt solutions of high ionic strength, enabling the membranes to work in a broader environmental window.
[ "Synthetic Chemistry and Materials", "Materials Engineering" ]
10.1039/C5CS00315F
Metallosupramolecular Receptors For Fullerene Binding And Release
Fullerene extracts are easily available from fullerene soot, but finding an efficient strategy to obtain them in pure form remains elusive, especially for higher fullerenes (Cx, x > 70). The properties of the latter remain unclear and their potential application to multiple research fields has not been developed mainly due to their purification difficulties. In this Tutorial Review we cover the use of molecular receptors for the separation of fullerenes by means of host–guest interactions. This strategy allows gaining selectivity, no specialized equipment is required and, ideally, recyclable systems can be designed. We focus on the metallosupramolecular receptors using the metal–ligand coordination approach, which offers a controlled and versatile strategy to design fullerene hosts, and the latest strategies to release the fullerene guest will be described. The field is probably in its beginnings but it is rapidly evolving and we are confident that this tutorial review will help researchers to rapidly gain a general overview of the main works and concepts that are leading this promising strategy and that may lead towards a useful methodology to purify fullerenes.
[ "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
W1974239490
Changes in the Multi‐Level Effects of Socio‐Economic Status on Reading Achievement in Sweden in 1991 and 2001
This study examines the changes in educational inequality at the school‐ and individual‐levels in 1991 and 2001. Comparisons are made between the IEA Reading Literacy Study 1991 and the so called 10‐Year Trend Study in PIRLS 2001. The between‐school differences in reading achievement variance and the size of the relationship between SES and reading achievement at school‐level are the two main focuses. Applying a two‐level structural equation modeling technique, it was found that the between‐school differences in reading achievement were greater in RLS 2001 than in RLS 1991, and the school SES effect has been strengthened over time. These changes indicate that educational inequality in Sweden has increased over time. Some possible explanations to these changes are discussed with reference to school reforms and demographic changes.
[ "The Social World and Its Interactions", "Individuals, Markets and Organisations" ]
Q4768737
ANDREA MALASPINA
THE ARCHITECTURAL FIRM ANDREA MALASPINA, ENROLLED IN THE ORDER OF ARCHITECTS, PLANNERS, LANDSCAPERS AND CONSERVATIONISTS OF THE PROVINCE OF GENOA N.3287 SINCE 2004 AND IN THE REGISTER OF PLANT VERIFIERS N.128 IN THE CHAMBER OF COMMERCE OF GENOA SINCE 2004 AND MEMBER OF THE MUNICIPAL AND PROVINCIAL CONSULTATION FOR PROBLEMS DEGLIHANDICAPPATI OF GENOA AND OF THE REGIONAL CONSULTATION OF THE LIGURIA REGION SINCE 2007. The MASTER EUROPEAN II LEVEL “URBAN QUALITY AND LIGHT PIANIFICATION” IN 2008.CERTIFICATION OF IMPORTANT STIMES CCS-B01 SECOND ISO 17024 FROM 2009.CONSULTING IN THE ACCESSIBILITY OF THE COMMUNITY OF GENOVA FROM 2010.ENERGICAL CERTIFICATION OF THE LIGURY REGION N.4346 FROM 2011.REGOGNISED EUROPEAN Valuer (TEGOVA & IsIVI) FROM 01/06/2014 N.61
[ "Products and Processes Engineering", "Human Mobility, Environment, and Space" ]
EP 14152581 A
Device for detecting differential currents, in particular of mixed currents of smoothed direct current and alternating currents
The device has two conductors (21) for load currents to be monitored and a magnetic current transformer, through which the conductors are guided. An oscillating circuit (22) is provided, which is designed as a square-wave generator and comprises two operational amplifiers and a current transformer (1) with two secondary windings (N13,N14). The secondary windings are electrically connected in series with an ohmic resistor. The operational amplifiers are arranged in a housing.
[ "Systems and Communication Engineering" ]
10.1063/1.4919645
Relaxation Dynamics In A Transient Network Fluid With Competing Gel And Glass Phases
We use computer simulations to study the relaxation dynamics of a model for oil-in-water microemulsion droplets linked with telechelic polymers. This system exhibits both gel and glass phases and we show that the competition between these two arrest mechanisms can result in a complex, three-step decay of the time correlation functions, controlled by two different localization lengthscales. For certain combinations of the parameters, this competition gives rise to an anomalous logarithmic decay of the correlation functions and a subdiffusive particle motion, which can be understood as a simple crossover effect between the two relaxation processes. We establish a simple criterion for this logarithmic decay to be observed. We also find a further logarithmically slow relaxation related to the relaxation of floppy clusters of particles in a crowded environment, in agreement with recent findings in other models for dense chemical gels. Finally, we characterize how the competition of gel and glass arrest mechanisms affects the dynamical heterogeneities and show that for certain combination of parameters these heterogeneities can be unusually large. By measuring the four-point dynamical susceptibility, we probe the cooperativity of the motion and find that with increasing coupling this cooperativity shows a maximum before it decreases again, indicating the change in the nature of the relaxation dynamics. Our results suggest that compressing gels to large densities produces novel arrested phases that have a new and complex dynamics.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
W1434946709
Electromigration in eutectic In-48Sn ball grid array (BGA) solder interconnections with Au/Ni/Cu pads
In this study, the microstructural evolution and interfacial reactions of the eutectic In-48Sn BGA solder bump interconnection with Au/Ni/Cu pads—under current stressing of 0.7 × 104 A/cm2 at ambient temperatures of 25 and 55 °C for up to 720 h—have been investigated. During electromigration, tin (Sn) acted as the “dominant diffusing species” and migrated from cathode to anode, while indium (In) migrated from anode to cathode. Finally, the phase segregation of Sn and In occurred. Sn-rich and In-rich layers accumulated at the anode side and cathode side of the solder bump, respectively. Due to the influence of current stressing, the simultaneous growth of the interfacial inter-metallic compounds (IMCs), at both the anode interface and the cathode interface, was accelerated. The anode IMC grew faster than the cathode IMC. By raising the ambient temperature, both the phase segregation and the interfacial IMC growth were enhanced. Based on the accumulation rate of the Sn-rich layer, which was calculated to be 7.85 × 10−10 cm/s at 25 °C and 2.07 × 10−9 cm/s at 55 °C, respectively, the products of the diffusivity and the effective charge number (DZ*) of Sn in In-48Sn solder was determined to be 1.17 × 10−10 cm2/s at 25 °C and 3.39 × 10−10 cm2/s at 55 °C, respectively.
[ "Condensed Matter Physics", "Materials Engineering" ]
W2052391344
Large-Eddy Simulations of Inhomogeneous Canopy Flows
The investigation of the turbulent flow within and above canopies is the key to understand the exchange processes between the atmosphere and vegetation. These processes influence the microclimate of plant growing and the atmospheric boundary layer (ABL). Reflecting the effects of forest edges, clearings and other inhomogeneities on the ABL lead to a better understanding of the propagation of tracer gases and the improvement of flux measurement methods. Within a Large-Eddy-Simulation (LES), these strong anisotropic turbulence effects generated by the vegetation have to be considered by subgrid-scale (SGS) models. The model used by the authors is a single equation transport model presented by Shaw and Schumann, [2] and still state-of-the-art. The vegetation is represented by a leaf area density (LAD) profile, which is often based only on spatially limited measurements and often only varies with height. The LAD distribution used for the presented simulations is obtained by terrestrial laser scanning methods and therefore of very high resultion for the whole solution domain of 192 m x 96 m x 120 m. The results are compared to wind tunnel and outdoor measurements to verify the assumptions of the SGS model.
[ "Earth System Science", "Products and Processes Engineering" ]
EP 2008001490 W
A GRIPPER WEAVING MACHINE PROVIDED WITH A BRINGER GRIPPER AND A DEFLECTING GUIDE
A gripper weaving machine provided with a bringer gripper (2) and a deflecting guide (3) on which a weft thread (4, 50) can rest before being brought into a weaving shed (9) by means of the bringer gripper (2), wherein the deflecting guide (3) comprises a groove (20) and the bringer gripper (2) comprises a thread clamp (40) and wherein the thread clamp (40) interacts with a thread guiding element (41 ) for the thread clamp (40) that moves, during the taking up of a weft thread (4, 50), through the groove (20) in order to take up a weft thread (4, 50) resting on the deflecting guide (3). A bringer gripper (2) and a deflecting guide (3) which are used in a gripper weaving machine.
[ "Products and Processes Engineering" ]
306589
Decoding the complexity of turbulence at its origin
Turbulence is the probably most complex and at the same time most relevant example of spatio-temporal disorder in nature. The transport of heat and mass in stars, the formation of planets, as well as flows in the earth atmosphere, oceans or around vehicles are all governed by turbulence. Despite its ubiquity our insights into this complex phenomenon are very limited. In contrast to many studies which are concerned with turbulent flows at high parameter values I will here use a different approach and investigate turbulence when it first arises and where it is the least complex. I will focus on canonical shear flows, comprising pipe, Couette and channel flows. I have recently determined the critical point for transition in pipe flow, which had posed a riddle for more than a century and inhibited further progress towards a fundamental understanding of turbulence close to onset. At first I will clarify if this transition generally applies to all canonical shear flows. Next I will explore links to non-equilibrium phase transitions in other areas of science by determining the critical exponents and the universality class of the onset of shear flow turbulence. I will investigate and identify further bifurcations the turbulent state experiences as it develops from a spatially intermittent to a space filling state. This will for the first time provide a complete picture of the onset of turbulence and establish links to turbulence studies at higher Reynolds numbers. Investigating the mechanisms leading to fully turbulent flow will not only give valuable insights into the nature of fluid turbulence but may also lead to new ways to control it. Finally I will exploit these insights and devise methods that completely relaminarize turbulent flows. Subduing turbulence is of great practical importance since frictional losses in turbulence are much larger than in the laminar state and hence relaminarization leads to substantial energy savings in transport problems.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1371/journal.pbio.1001604
Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte-Neuron Communication
Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration" ]
W1534923516
The Female Genital Self-Image Scale (FGSIS): Validation among a Sample of Female College Students
Gynecological exams continue to be underused among young women, possibly due to a woman's genital self-image.The purpose of this study was to (i) examine college women's genital image using the Female Genital Self-Image Scale (FGSIS); (ii) assess the reliability, validity, and factor structure of data collected on the FGSIS; and (iii) examine the relationship between FGSIS scores and gynecological exam behaviors.Data were collected in November/December 2010 from 450 undergraduate women.Descriptive statistics were utilized to analyze demographic variables. A comprehensive psychometric assessment of the FGSIS included: (i) a reliability assessment of internal consistency; (ii) conducting a confirmatory factor analysis (CFA) to identify factor structure; and (iii) structural equation modeling and predictive discriminant analysis to asses the predictive qualities of the FGSIS on gynecological exam behavior.CFA analyses yielded a two-factor FGSIS structure: X(2) (12, N=450)=49.77; P<0.001, Root Mean Square Error of Approximation=0.08, Comparative Fit Index=0.98, Normed Fit Index=0.97. Reliability assessments indicated very good internal consistency for the scale (α=0.89), as well as for factor one (α=0.86) and factor two (α=0.82). Women who engaged in at least one gynecological exam during the past 24 months had a significantly more positive genital self-image than those who had not (t (449)=-2.501; P=0.01).Data collected using the FGSIS were found to be valid and reliable in this sample, further supporting the utility of the scale and aiding in the understanding of college women's genital image using an underlying two-factor approach. This has important implications for the development of sexual health and women's health programs and discussions. Specifically, a two-factor FGSIS can aid medical and health professionals in better understanding relationships between genital image and gynecological exam behavior.
[ "The Social World and Its Interactions", "Prevention, Diagnosis and Treatment of Human Diseases", "The Human Mind and Its Complexity" ]
10.1016/j.ceb.2014.06.010
Circadian control of tissue homeostasis and adult stem cells
The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing" ]
10.1137/110827867
Transmission Eigenvalues For Elliptic Operators
A reduction of the transmission eigenvalue problem for multiplicative sign-definite perturbations of elliptic operators with constant coefficients to an eigenvalue problem for a non-self-adjoint compact operator is given. Sufficient conditions for the existence of transmission eigenvalues and completeness of generalized eigenstates for the transmission eigenvalue problem are derived. In the trace class case, the generic existence of transmission eigenvalues is established.
[ "Mathematics" ]
W2507693329
EU policy on the move – mobility and domestic translation of the European Union’s renewable energy policy
ABSTRACTWe discuss how the EU’s Renewable Energy Directive was designed to be mobile, and how it was moved to and implemented in Finland by translating it to enhance wood-based energy production through specific subsidies. We study policy-making as a mobile process, which approach has its original roots in political science and more recent basis in political geography. The article aims to develop conceptual understanding of how the mobility of a supranational policy is generated and how a policy is translated into complex and contentious geographical contexts. We aim to show that mobility of a directive is enabled by an empty governance space which is aimed to be ‘filled in’ in each spatial context, and that the filling in process makes each translation a contentious and path-dependent process. In Finland, the selected policy tools and practices continued the path-dependent ways of favouring forestry industry’s traditional position as the primary utiliser of forest resources.
[ "Human Mobility, Environment, and Space", "Institutions, Governance and Legal Systems" ]
637611
Yufe transforming research and innovation through europe-wide knowledge transfer
As part of the European Research Area vision, the European Commission is aiming to see the necessary transformations in R&I that will include the promotion of citizen science and societal engagement, the mainstreaming of Open Science practices, the fostering of brain and knowledge circulation, strengthening of academia-business collaboration and embodiment in a glocal Research and Innovation (R&I) ecosystem. The YUFE (Young Universities for the Future of Europe) alliance embraces in YUFERING this challenge by effectively contributing to pilot these needed transformations to improve and harmonise the conditions for R&I in Europe. Focusing on key elements of the ERA and in full alignment with the relevant SwafS call for proposals, YUFERING proposes ground-breaking transformation actions that will bring the partners one step closer to creating and realising a shared robust R&I vision. These transformations comprise community engaged R&I, flipped knowledge transfer to the enterprise sector and the society at large, shared R&I agendas, support structures and research infrastructures, as well as common open science strategies and new incentive and reward schemes for researchers based on the new open science era. The European cooperation and transformation in R&I (next to education) that is objective of the European Universities Initiative is unavoidably dependent on multilateralism, synergy and support from the EU as well as Member States. In YUFERING, the YUFE partners will also work towards assessing the legal, regulatory and financial conditions that are relevant towards the creation of a stronger ERA and will identify recommendations towards transformation needed to make sharing of capacity and resources possible and attractive for academics and institutional/private funders. Within YUFERING, the alliance will explore synergies with other ‘European Universities’ to facilitate collaboration in relevant activities and towards addressing shared challenges and barriers.
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions", "Human Mobility, Environment, and Space" ]
10.1007/978-3-319-04849-9_18
Zeta Functions And Continuous Time Dynamics
The purpose of this survey is to introduce the reader to the relation between continuous time hyperbolic systems and zeta functions, focusing on Anosov flows and billiards as seen through the lenses of transfer operators.
[ "Mathematics" ]