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10.1093/nar/gku578 | Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6 | Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance pathway that recognizes mRNAs with premature stop codons and targets them for rapid degradation. Evidence from previous studies has converged on UPF1 as the central NMD factor. In human cells, the SMG1 kinase phosphorylates UPF1 at the N-terminal and C-terminal tails, in turn allowing the recruitment of the NMD factors SMG5, SMG6 and SMG7. To understand the molecular mechanisms, we recapitulated these steps of NMDin vitro using purified components. We find that a short C-terminal segment of phosphorylated UPF1 containing the last two Ser-Gln motifs is recognized by the heterodimer of SMG5 and SMG7 14-3-3-like proteins. In contrast, the SMG6 14-3-3-like domain is amonomer. The crystal structure indicates that the phosphoserine binding site of the SMG6 14-3-3-like domain is similar to that of SMG5 and can mediate a weak phospho-dependent interaction with UPF1. The dominant SMG6-UPF1 interaction is mediated by a low-complexity region bordering the 14-3-3-like domain of SMG6 and by the helicase domain and Cterminal tail of UPF1. This interaction is phosphorylation independent. Our study demonstrates that SMG5-SMG7 and SMG6 exhibit different and nonoverlapping modes of UPF1 recognition, thus pointing at distinguished roles in integrating the complex NMD interaction network. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1109/TBME.2018.2813015 | Uncertainty Aware Organ Classification For Surgical Data Science Applications In Laparoscopy | Objective: Surgical data science is evolving into a research field that aims to observe everything occurring within and around the treatment process to provide situation-aware data-driven assistance. In the context of endoscopic video analysis, the accurate classification of organs in the field of view of the camera proffers a technical challenge. Herein, we propose a new approach to anatomical structure classification and image tagging that features an intrinsic measure of confidence to estimate its own performance with high reliability and which can be applied to both RGB and multispectral imaging (MI) data. Methods: Organ recognition is performed using a superpixel classification strategy based on textural and reflectance information. Classification confidence is estimated by analyzing the dispersion of class probabilities. Assessment of the proposed technology is performed through a comprehensive in vivo study with seven pigs. Results: When applied to image tagging, mean accuracy in our experiments increased from 65% (RGB) and 80% (MI) to 90% (RGB) and 96% (MI) with the confidence measure. Conclusion: Results showed that the confidence measure had a significant influence on the classification accuracy, and MI data are better suited for anatomical structure labeling than RGB data. Significance: This paper significantly enhances the state of art in automatic labeling of endoscopic videos by introducing the use of the confidence metric, and by being the first study to use MI data for in vivo laparoscopic tissue classification. The data of our experiments will be released as the first in vivo MI dataset upon publication of this paper. | [
"Computer Science and Informatics",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1038/ng.2293 | Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk | We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1. 14 × 10 -10), 11q13. 4 (rs3824999, intronic to POLD3; P = 3. 65 × 10 -10) and Xp22. 2 (rs5934683, near SHROOM2; P = 7. 30 × 10 -10) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
341089 | Understanding the roles of kainate receptors in the hippocampus | Kainate receptors (KARs) are often regarded as the last frontier of glutamate receptor research, since much less is known about their physiological roles compared with that of the other glutamate receptor subtypes. This field of research is very important not just because of the unique role that KARs play in neuronal function, including specific forms of synaptic plasticity, but because of the increasing evidence that KARs are involved in a plethora of brain diseases and that KAR antagonists are promising novel therapeutic targets. I propose to lead a highly multidisciplinary approach, in collaboration with colleagues at Bristol and strategic collaborators worldwide, to develop novel pharmacological and genetic tools, which will be rapidly disseminated to the neuroscience community. These tools will be used here to test hypotheses regarding functions of KARs in granule cells (GCs) in the dentate gyrus of the hippocampal formation, with a focus on mossy fibre long-term potentiation (LTP). We propose four interrelated objectives: (i) to develop potent and selective antagonists for the GluK2 subunit of KARs, (ii) to generate GC specific knockouts of the five KAR subunits, by floxing GluK1-5 and crossing with a GC-specific Cre recombinase mouse line, (iii) to use these and existing tools in a combined pharmacological and genetic approach, to understand the functions of KARs at mossy fibre synapses in acute and organotypic hippocampal slices. A new development will be to record simultaneously from synaptically coupled GC-CA3 neuronal pairs and to image Ca2+ from participating mossy fibre boutons, (iv) to extend these investigations to the study of mossy fibre function, in particular LTP, in anaesthetised animals and to establish the function of mossy fibre LTP in hippocampus-dependent learning and memory. Although highly ambitious, the proposal is based on a long track record of KAR research by the PI and his collaborators plus a substantial amount of preliminary data. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1128/microbiolspec.MDNA3-0061-2014 | The influence of LINE-1 and SINE retrotransposons on mammalian genomes | Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ~17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
interreg_2001 | Central European SME Gateway to Key-enabling Technology
Infrastructures - Sparking a new Transnational KET Innovation Ecosystem | CE as model region for an access & service network for SME to bring smart solutions from idea to market readiness Smart solutions derive from applying key enabling technologies (KET) such as micro-nanoelectronics or optical techn. compounds and advanced materials and thus lifting products, processes and services to a new techn. level. SME in food, transport & health are now able to access newest infrastructures, labs & techn. services through regional channels: KET access & service points at business support or applied research organisations in 8 CE regions join forces to act in synergy & across national borders, to ensure that SME are connected & serviced by the best fitting supplier, even if located abroad. Regional access bridges cultural & language barriers. Standard operations but tailored to each single SME ensure reliability & trust.
5 business support organisations from PL, CR, CZ, DE, IT & 3 applied research institutes from AT, HU & SL develop & test the necessary operational models & tools. The Lead Partners research on the EU KET inventory of technol. infrastructures revealed high disparities for available KET services in CE. The project KETGATE will change that, enabling transnational KET techn. collaborations among RTOs to bridge service gaps and enable SME across CE to access high level techn. services. SME can thus test new technol. using innovative machines & laboratories, before they invest in new machines or techn., which may not work for them.
Once validated, collaboration agreements strengthen the KET access & service network. The tools & services, business & collaboration models are available as starter-kits & toolboxes, so that the network can grow towards a KET Innovation Ecosystem, enabling SME to bring smarter solutions quicker to market, levering private and public investments and supporting the dynamic development of KET knowhow & application in CE. | [
"Products and Processes Engineering",
"Materials Engineering",
"Systems and Communication Engineering"
]
|
10.1002/anie.201311024 | Iron-catalyzed C(sp<sup>2</sup>)-H and C(sp<sup>3</sup>)-H arylation by triazole assistance | Modular 1,2,3-triazoles enabled iron-catalyzed C-H arylations with broad scope. The novel triazole-based bidentate auxiliary is easily accessible in a highly modular fashion and allowed for user-friendly iron-catalyzed C(sp 2)-H functionalizations of arenes and alkenes with excellent chemo- and diastereoselectivities. The versatile iron catalyst also proved applicable for challenging C(sp3)-H functionalizations, and proceeds by an organometallic mode of action. The triazole-assisted C-H activation strategy occurred under remarkably mild reaction conditions, and the auxiliary was easily removed in a traceless fashion. Intriguingly, the triazole group proved superior to previously used auxiliaries. With a little help: A versatile iron catalyst allows the arylation of C(sp2)-H and C(sp3)-H bonds in the presence of a modular and removable triazolyldimethylmethyl (TAM) auxiliary, whose structure can be varied through 1,3-dipolar azide-alkyne cycloadditions. | [
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
W1978315522 | Highly Diastereoselective Samarium Diiodide Induced Ketyl Cyclisations of Indole and Pyrrole Derivatives - Scope and Limitations | Here we summarise our results for SmI2-induced 5-exo-trig to 8-exo-trig reductive cyclisations of suitably substituted indole and pyrrole derivatives. All precursors were easily prepared by simple N-alkylation or N-acylation of indole and pyrrole derivatives with the corresponding iodo alkanones, acid chlorides or lactones. The SmI2-induced cyclisations in most cases provided tri- and tetracyclic derivatives, even in the absence of HMPA, in good to very good yields and with excellent diastereoselectivities. Extensive investigations of the reaction conditions revealed that in the presence of different proton sources SmI2-induced cyclisations afforded mainly one major type of diastereomer (thermodynamic control), so the formation of three or four stereogenic centres is controlled in one step. The mechanism of the SmI2-induced ketyl coupling is discussed in more detail on the basis of these observations and two possible mechanistic pathways are compared. The assumed intermediate samarium enolates were also trapped with allyl iodide, furnishing interesting polycyclic N-heterocycles bearing newly formed quaternary centres as single diastereomers. | [
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
]
|
W1991997530 | Towards “mouldable code” via nested code graph transformation | Program transformation is currently de facto restricted to abstract syntax tree rewriting. However, many program transformation patterns, in particular in the realm of high-performance code generation, can more naturally be understood and expressed as graph transformations. We describe the conceptual organisation of a system based on application of algebraic graph transformation rules to data-flow and control-flow graphs, and outline the work, both theoretical and of implementation nature, that still needs to be done to realise this long-term project. • Many program transformations are usefully understood as flow graph transformations. • Correctness proofs require semantics in Kleene algebras and relational categories. • Different layers of nested flow graphs use common data structures. • Graph-based transformation design will enable complex code adaptation mechanisms. • The overall approach goes back to Gunther Schmidt's ideas of “mouldable code”. | [
"Computer Science and Informatics",
"Mathematics"
]
|
10.1016/j.gca.2017.09.005 | Differentiation and magmatic activity in Vesta evidenced by <sup>26</sup>Al-<sup>26</sup>Mg dating in eucrites and diogenites | The 26Al-26Mg short-lived chronometer has been widely used for dating ancient objects in studying the early Solar System. Here, we use this chronometer to investigate and refine the geological history of the asteroid 4-Vesta. Ten meteorites widely believed to come from Vesta (4 basaltic eucrites, 3 cumulate eucrites and 3 diogenites) and the unique achondrite Asuka 881394 were selected for this study. All samples were analyzed for their δ26Mg∗ and 27Al/24Mg ratios, in order to construct both whole rock and model whole rock isochrons. Mineral separation was performed on 8 of the HED's in order to obtain internal isochrons. While whole rock Al-Mg analyses of HED's plot on a regression that could be interpreted as a vestan planetary isochron, internal mineral isochrons indicate a more complex history. Crystallization ages obtained from internal 26Al-26Mg systematic in basaltic eucrites show that Vesta's upper crust was formed during a short period of magmatic activity at 2. 66-0. 58+1. 39 million years (Ma) after Calcium-Aluminum inclusions (after CAI). We also suggest that impact metamorphism and subsequent age resetting could have taken place at the surface of Vesta while 26Al was still extant. Cumulate eucrites crystallized progressively from 5. 48-0. 60+1. 56 to >7. 25 Ma after CAI. Model ages obtained for both basaltic and cumulate eucrites are similar and suggest that the timing of differentiation of a common eucrite source from a chondritic body can be modeled at 2. 88-0. 12+0. 14 Ma after CAI, i. e. contemporaneously from the onset of the basaltic eucritic crust. Based on their cumulate texture, we suggest cumulate eucrites were likely formed deeper in the crust of Vesta. Diogenites have a more complicated history and their 26Al-26Mg systematics show that they likely formed after the complete decay of 26Al and thus are younger than eucrites. This refined chronology for eucrites and diogenites is consistent with a short magma ocean stage on 4-Vesta from which the basaltic eucrites rapidly crystallized. In order to explain the younger age and the complex history of diogenites, we postulate that a second episode of magmatism was possibly triggered by a mantle overturn. We bring a refined chronology of the geological history of Vesta that shows that the asteroid has known a more-complex differentiation than previously thought. | [
"Universe Sciences",
"Earth System Science"
]
|
10.1182/blood.2020006738 | Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency | Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority of patients (90%) were EBV+ at diagnosis, but only ∼30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one patients (43%) developed autoinflammatory features including uveitis, arthritis, and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1029/2012GL052002 | Comparison Of Ray And Adjoint Based Sensitivity Kernels For Body Wave Seismic Tomography | [1] We compare finite-frequency sensitivity kernels computed from ray-theoretical wavefields (“banana-doughnut” kernels) and from full waveform computations (often called “adjoint” kernels) in order to evaluate resolution, accuracy and computational cost. We focus here on body-wave seismic tomography at regional and local scales. Our results show that: (1) for homogeneous reference media, ray-based and adjoint kernels agree except for the expected differences in the regions close to the source and the receiver, where near-field contributions are neglected in the ray-based kernels; (2) for a smooth 3D background velocity model, the differences in predicted delay times for the two methods are generally well below 10 % of the delay for P waves, though as much as 20 % for S-waves, suggesting that extra care should be taken when performing S-wave tomography with ray-based “banana doughnut” kernels. | [
"Earth System Science",
"Mathematics"
]
|
10.18632/oncotarget.14895 | The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types | For many years, defects in the ribosome have been associated to cancer. Recently, somatic mutations and deletions affecting ribosomal protein genes were identified in a few leukemias and solid tumor types. However, systematic analysis of all 81 known ribosomal protein genes across cancer types is lacking. We screened mutation and copy number data of respectively 4926 and 7322 samples from 16 cancer types and identified six altered genes (RPL5, RPL11, RPL23A, RPS5, RPS20 and RPSA). RPL5 was located at a significant peak of heterozygous deletion or mutated in 11% of glioblastoma, 28% of melanoma and 34% of breast cancer samples. Moreover, patients with low RPL5 expression displayed worse overall survival in glioblastoma and in one breast cancer cohort. RPL5 knockdown in breast cancer cell lines enhanced G2/M cell cycle progression and accelerated tumor progression in a xenograft mouse model. Interestingly, our data suggest that the tumor suppressor role of RPL5 is not only mediated by its known function as TP53 or c-MYC regulator. In conclusion, RPL5 heterozygous inactivation occurs at high incidence (11-34%) in multiple tumor types, currently representing the most common somatic ribosomal protein defect in cancer, and we demonstrate a tumor suppressor role for RPL5 in breast cancer. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
]
|
10.1364/OE.17.019926 | Terahertz Ambipolar Dual Wavelength Quantum Cascade Laser | Terahertz frequency quantum cascade lasers (THz QCLs) are compact solid-state sources of terahertz radiation that were first demonstrated in 2002. They have a broad range of potential applications ranging from gas sensing and non-destructive testing, through to security and medical imaging, with many polycrystalline compounds having distinct fingerprint spectra in the terahertz frequency range. In this article, we demonstrate an electrically-switchable dual-wavelength THz QCL which will enable spectroscopic information to be obtained within a THz QCL-based imaging system. The device uses the same active region for both emission wavelengths: in forward bias, the laser emits at 2. 3 THz; in reverse bias, it emits at 4 THz. The corresponding threshold current densities are 490 A/cm2 and 330 A/cm2, respectively, with maximum operating temperatures of 98K and 120 K. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Systems and Communication Engineering"
]
|
10.1016/j.cell.2017.08.018 | Mitochondrial Priming by CD28 | T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Early CD28-dependent mitochondrial engagement is needed for T cells to remodel cristae, develop SRC, and rapidly produce cytokines upon restimulation—cardinal features of protective memory T cells. Our data show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity that is essential for future T cell responses. Costimulatory signals during the initial phase of T cell activation prime mitochondria with latent metabolic capacity essential for future T cell responses. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
788185 | Artificial designer materials | Constructing designer materials where the atomic geometry, interactions, magnetism and other relevant parameters can be precisely controlled is becoming reality. I will reach this aim by positioning every atom with the tip of a scanning probe microscope, or by using molecular self-assembly to reach the desired structures. I will realize and engineer several novel quantum materials hosting exotic electronic phases: 2D topological insulators in metal-organic frameworks (MOF) and 2D topological superconductors in hybrid molecule-superconductor structures. These classes of materials have not yet been experimentally realized but could enable novel spintronic and quantum computing devices. In addition, we will realize a tuneable platform for quantum simulation in solid-state artificial lattices, which could open a whole new area in this field.
I will employ a broad experimental approach to reach the above targets by utilizing molecular self-assembly and scanning probe microscopy -based atom/molecule manipulation. The systems are characterized using low-temperature atomic force microscopy (AFM) and scanning tunneling microscopy (STM). My group is one of the leading groups in these topics globally. We have initial results on the topics discussed in this proposal and are thus in a unique position to make ground-breaking contributions in realizing designer quantum materials.
The artificial designer materials we study are characterized by the engineered electronic response with atomically precise geometries, lattice symmetries and controlled interactions. Such ingredients can result in ultimately controllable materials that have large, robust and quick responses to small stimuli with applications in nanoelectronics, flexible electronics, high-selectivity and high-sensitivity sensors, and optoelectronic components. Longer term, the biggest impact is expected through a profound change in the way we view materials and what can be achieved through designer materials approach. | [
"Condensed Matter Physics",
"Materials Engineering",
"Synthetic Chemistry and Materials"
]
|
10.1080/10564934.2016.1248231 | Teachers In Schools With Low Socioeconomic Composition Are They Really That Different | This article aims to assess whether differences in teacher characteristics vary with differences in socioeconomic compositions of schools. We conducted correlation analyses on administrative data from the French-speaking education system in Belgium. This database regroups more than 20,000 teachers in 1,630 elementary schools. We selected indicators to measure the link between schools’ socioeconomic composition and a set of dimensions of teachers’ profile such as experience, job security, and stability. The results confirm that some of these dimensions are linked to the school composition. The findings highlight the relevance of considering segmentation of the school market when studying the topic. | [
"The Social World and Its Interactions"
]
|
W2769674793 | Experimental validation of plastic constitutive hardening relationship based upon the direction of the Net Burgers Density Vector | Abstract We present a new methodology for experimental validation of single crystal plasticity constitutive relationships based upon spatially resolved measurements of the direction of the Net Burgers Density Vector, which we refer to as the β -field. The β -variable contains information about the active slip systems as well as the ratios of the Geometrically Necessary Dislocation (GND) densities on the active slip systems. We demonstrate the methodology by comparing single crystal plasticity finite element simulations of plane strain wedge indentations into face-centered cubic nickel to detailed experimental measurements of the β -field. We employ the classical Peirce–Asaro–Needleman (PAN) hardening model in this study due to the straightforward physical interpretation of its constitutive parameters that include latent hardening ratio, initial hardening modulus and the saturation stress. The saturation stress and the initial hardening modulus have relatively large influence on the β -variable compared to the latent hardening ratio. A change in the initial hardening modulus leads to a shift in the boundaries of plastic slip sectors with the plastically deforming region. As the saturation strength varies, both the magnitude of the β -variable and the boundaries of the plastic slip sectors change. We thus demonstrate that the β -variable is sensitive to changes in the constitutive parameters making the variable suitable for validation purposes. We identify a set of constitutive parameters that are consistent with the β -field obtained from the experiment. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1016/j.polymer.2010.03.032 | Kinetics of thermally-induced conformational transitions in soybean protein films | The thermally-induced conformational transitions of soybean protein films were studied as the films were heated under isothermal conditions in the range 40-100 °C. By comparing the kinetics of protein-water interactions as a function of temperature using time-resolved Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DTMA) measurements on soybean protein films, we have shown that simply evaporating water from the film (TGA) is insufficient to explain the rate of conformational changes (FTIR and DMTA). We suggest that an elastic instability condition of denaturation or glass transition events in water-amide interactions is the governing mechanism for conformational changes that allows the evolution of disordered structures into more ordered secondary structures, thereby controlling the changes in physical properties such as stiffness and water sensitivity. | [
"Physical and Analytical Chemical Sciences",
"Materials Engineering"
]
|
W1996994431 | P-1229 - The effect of premorbid function on symptoms severity in first - episode of schizophrenia: an egyptian study | Introduction Psychiatric research focuses on development of psychosis and first- episode schizophrenia, early detection and Premorbid adjustment are of interest because it may reduce the heterogeneity of the disorder and may have predictive value. Aim To study the Premorbid functioning in first episode schizophrenic patients and its relation with symptoms severity, cognitive and executive function as well as it s predictive measure for short term degree of improvement. Subjects and methods Fifty patients diagnosed according to ICD -10 criteria as first episode schizophrenia were conducted to Positive and Negative Syndrome Scale (PANAS), Modified Premorbid Adjustment scale (MPAS), Social Readjustment Rating to evaluate severity and pattern of the symptoms and Premorbid function as well as psychometric assessment including IQ, Wisconsin Card Sorting test (WCST) and Eysenck personality Questioner (EPQ). Results Seventy percent of patients showed a disturbance in Premorbid function 38 % had deteriorating Premorbid functioning while 32% have stable poor Premorbid function The deterioration of Premorbid function was statistically correlated with negative symptoms, thought disturbance, and anergia as well as poor total score of WCST and low IQ. Impairment of executive functions were related to severe paranoid symptom and aggression. Conclusion Our study emphasized the importance of measuring Premorbid adjustment to people at risk for schizophrenia in order to detect more precisely the earliest symptoms for early prevention of schizophrenic disorder. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1016/j.colsurfb.2012.06.028 | Thin phosphatidylcholine films as background surfaces with further possibilities of functionalization for biomedical applications | Non-specific adsorption is a crucial problem in the biomedical field. To produce surfaces avoiding this phenomenon, we functionalized thin (7-180. nm) poly(methylhydrosiloxane) (PMHS) network films at room temperature (≈20. °C) with phospholipids (PL) bearing a phosphorylcholine head. Regardless of their mode of preparation (casting or immersion), all surfaces appeared to be very hydrophilic with a captive air-bubble contact angle stabilized around 40°. The thin films were protein-repellent in phosphate saline buffer pH 7. 4 according to analysis by normal scanning confocal fluorescence. Neither was any adsorption or spreading of l-α-phosphatidylcholine liposomes on such films observed. In addition, amino functional groups could be easily attached to the surface remaining available for further functionalization. | [
"Materials Engineering",
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
]
|
W2058710384 | P.6.7 Wide phenotypic spectrum of SMA with lower limbs predominance due to mutations in the tail domain of DYNC1H1 gene: A case series | A relatively common neurogenic condition is the autosomal dominant congenital Spinal Muscular Atrophy, mainly affecting the lower limbs (SMA-LED). A proportion of patients with SMA-LED carry mutations in the tail domain of the Cytoplasmic Dynein Heavy Chain 1 (DYNC1H1). Mutations located in the same DYNC1H1 domain have also been described in a family with Charcot–Marie–Tooth, while mutations located in other domains have been described in 2 patients with mental retardation and variable neuronal migration defects but no obvious SMA. To expand the clinical and imaging phenotype of SMA-LED due to DYNC1H1 mutations. We report a series of 10 cases from 7 families, carrying mutations in the tail domain of DYNC1H1, mostly with autosomal dominant inheritance, characterized by congenital/very early onset and similar clinical presentation, frequent association with cognitive impairment and variable clinical severity. In some of these cases imaging of the brain (MRI) and the muscles (lower limbs MRI) was obtained. In most cases with cognitive impairment the brain MRI showed neuronal migration defects resulting in polymicrogyria or cortical dysplasia. In all cases the muscle MRI showed distinctive features characterized by selective sparing and relative hypertrophy of the adductor longus and of the semitendinosus muscles at the thigh level, while at the calf level there was diffuse involvement with relative sparing of the anterior muscles. We describe for the first time a series of cases with both congenital SMA-LED and neuronal migration defects coexisting as a result of a mutation in DYNC1H1. Furthermore we confirm a specific pattern of muscular involvement in this condition, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions. Further studies are necessary to clarify whether the location and nature of the DYNC1H1 mutations play a role in the wide phenotypic spectrum that is emerging for this condition. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1016/j.jpubeco.2017.09.002 | Durable coalitions and communication: Public versus private negotiations | We present a laboratory experiment to study the effect of communication on durable coalitions — coalitions that support the same allocation from one period to the next. We study a bargaining setting where the status quo policy is determined by the policy implemented in the previous period. Our main experimental treatment is the opportunity for subjects to negotiate with one another through unrestricted cheap-talk communication before a proposal is made and comes to a vote. We compare committees with no communication, committees where communication is public and messages are observed by all committee members, and committees where communication is private and any committee member can send a private message to any other committee member. We find that the opportunity to communicate has a significant impact on outcomes and coalitions. When communication is public, there are more universal coalitions and fewer majoritarian coalitions. With private communication, there are more majoritarian coalitions and fewer universal coalitions. With either type of communication coalitions occur more frequently and last longer than with no communication. The volume and content of communication is correlated with coalition type. These findings suggest a coordination role for communication that varies with the mode of communication. | [
"Individuals, Markets and Organisations",
"The Social World and Its Interactions"
]
|
10.1039/C1JM10197H | Janus Particle Arrays With Multiple Structural Controlling Abilities Synthesized By Seed Directed Deposition | Janus particle arrays have attracted much investigation interest in recent years due to their wide application potentialities. Here, we introduce a new protocol to synthesize Janus particle arrays depending on seed-directed eletrophoretic deposition on monolayer colloidal crystal (MCC) templates. The size and feature of the Janus particles can be conveniently tailored by selecting different sized polystyrene spheres and deposition current densities and/or times, respectively. Non-close-packed Janus particle arrays can be prepared by adopting plasma treated monolayer colloidal crystal templates. The spacing between neighbouring Janus particles in the ordered array is determined by the plasma etching time of the MCC template. Due to the symmetry breaking and the plasmon hybridization, the Janus particle arrays show interesting plasmonic properties. They have multiple plasmonic peaks and have infrared absorption, making them have applications in sensing and bio-related areas. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1080/08905495.2017.1335157 | Women Editors And The Rise Of The Illustrated Fashion Press In The Nineteenth Century | In the second half of the nineteenth century, a new type of magazine emerged in Europe and the United States. Fashion—a staple of up-market women’s periodicals since the late eighteenth century—was. . . | [
"Texts and Concepts",
"The Study of the Human Past",
"Studies of Cultures and Arts"
]
|
W2151412165 | Do iPads promote symbolic understanding and word learning in children with autism? | The use of the Apple iPad has skyrocketed in educational settings, along with largely unsubstantiated claims of its efficacy for learning and communication in children with autism spectrum disorder (ASD). Here, we examine whether children with ASD are better able to learn new word-referent relations using an iPad or a traditional picture book. We also examine the hypothesis that presenting multiple, differently colored, exemplars of a target referent will promote adaptive label generalization compared to the use of a single exemplar. Sixteen minimally verbal children with ASD were taught a new word in four within-subjects conditions, which varied by media (iPad vs. book) and content (single vs. multiple exemplar presentation). Children were then tested on the ability to symbolically relate the word to a 3-D referent (real-life depicted object) and generalize it to a differently colored category member (another similarly shaped object). The extent of symbolic understanding did not differ between the two media, and levels of generalization did not differ across conditions. However, presentation of multiple exemplars increased the rate that children with ASD extended labels from pictures to depicted objects. Our findings are discussed in terms of the importance of content to picture-based learning and the potential benefits and challenges of using the Apple iPad as an educational resource for children with ASD. | [
"The Human Mind and Its Complexity",
"Neuroscience and Disorders of the Nervous System"
]
|
W2940737966 | High-Performance Defunctionalisation in Futhark | General-purpose massively parallel processors, such as GPUs, have become common, but are difficult to program. Pure functional programming can be a solution, as it guarantees referential transparency, and provides useful combinators for expressing data-parallel computations. Unfortunately, higher-order functions cannot be efficiently implemented on GPUs by the usual means. In this paper, we present a defunctionalisation transformation that relies on type-based restrictions on the use of expressions of functional type, such that we can completely eliminate higher-order functions in all cases, without introducing any branching. We prove the correctness of the transformation and discuss its implementation in Futhark, a data-parallel functional language that generates GPU code. The use of these restricted higher-order functions has no impact on run-time performance, and we argue that we gain many of the benefits of general higher-order functions, without in most practical cases being hindered by the restrictions. | [
"Computer Science and Informatics"
]
|
10.1177/0956797619842550 | Rationality In Joint Action Maximizing Coefficiency In Coordination | When people perform simple actions, they often behave efficiently, minimizing the costs of movement for the expected benefit. The present study addressed the question of whether this efficiency scales up to dyads working together to achieve a shared goal: Do people act efficiently as a group (i. e. , coefficiently), or do they minimize their own or their partner's individual costs even if this increases the overall cost for the group? We devised a novel, touch-screen-based, sequential object-transfer task to measure how people choose between different paths to coordinate with a partner. Across multiple experiments, we found that participants did not simply minimize their own or their partner's movement costs but made coefficient decisions about paths, which ensured that the aggregate costs of movement for the dyad were minimized. These results suggest that people are able and motivated to make coefficient, collectively rational decisions when acting together. | [
"The Human Mind and Its Complexity",
"The Social World and Its Interactions"
]
|
715767 | MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling | While access to 3D-printing technology becomes ubiquitous and provides revolutionary possibilities for fabricating complex, functional, multi-material objects with stunning properties, its potential impact is currently significantly limited due to the lack of efficient and intuitive methods for content creation. Existing tools are usually restricted to expert users, have been developed based on the capabilities of traditional manufacturing processes, and do not sufficiently take fabrication constraints into account. Scientifically, we are facing the fundamental challenge that existing simulation techniques and design approaches for predicting the physical properties of materials and objects at the resolution of modern 3D printers are too slow and do not scale with increasing object complexity. The problem is extremely challenging because real world-materials exhibit extraordinary variety and complexity.
To address these challenges, I suggest a novel computational approach that facilitates intuitive design, accurate and fast simulation techniques, and a functional representation of 3D content. I propose a multi-scale representation of functional goals and hybrid models that describes the physical behavior at a coarse scale and the relationship to the underlying material composition at the resolution of the 3D printer. My approach is to combine data-driven and physically-based modeling, providing both the required speed and accuracy through smart precomputations and tailored simulation techniques that operate on the data. A key aspect of this modeling and simulation approach is to identify domains that are sufficiently low-dimensional to be correctly sampled. Subsequently, I propose the fundamental re-thinking of the workflow, leading to solutions that allow synthesizing model instances optimized on-the-fly for a specific output device. The principal applicability will be evaluated for functional goals, such as appearance, deformation, and sensing capabilities. | [
"Computer Science and Informatics",
"Materials Engineering",
"Products and Processes Engineering"
]
|
W1906279513 | Practical considerations in parasite control programmes for cats and dogs | Parasite control is required for a number of parasites infecting cats and dogs, both for animal and human health. Pet owners may obtain information from many sources such as pet shops, pharmacies, the internet and word of mouth, which can lead to confusion over which parasites are of concern and what control measures are required. It is the role of veterinary professionals to assess the needs of clients and their pets, and make specific recommendations for them. In doing so, client and pet health are improved while client bonding to the practice, and sales of parasiticides, may be increased. This article considers the factors that need to be assessed in giving effective parasite control advice. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
225624 | High speed afm imaging of molecular processes inside living cells | Imaging the inside of living cells with single nanometre resolution has been a long-standing dream in bio-microscopy. Direct observation of changes to molecular networks inside of living cells would revolutionize the way we study structural cell biology. Unfortunately, no such tool exists. Atomic force microscopy (AFM) is the closest we have, to nanoscale functional imaging of cells in their native, fluid environment. However, it is limited to imaging the outside of the cell.
With InCell, I will remedy this by developing an AFM capable of imaging the inside of living cells. The approach is based on a microfabricated high speed AFM cantilever encased in a double barrel patch-clamp shell. The patch clamp shell seals onto the plasma membrane of the cell, so that the tip of the AFM cantilever can enter the cell without causing the cytosol to leak out. Parasitic interactions of the AFM tip with the cytosol will be subtracted from the cantilever deflection signal, using high speed photo-thermal off-resonance tapping (PT-ORT), a novel AFM mode we have recently developed in my lab. This allows the extraction of the true tip-sample interaction, even in viscous fluids. A dedicated InCell HS-AFM combined with confocal optical microscopy will be used to guide the InCell cantilever inside the cell to the area of interest.
Using this minimally invasive technique we will study the formation of clathrin coated pits, a crucial part of endocytosis. By imaging for the first time the nanoscale dynamics of this process in living cells, we aim to answer fundamental questions about the clathrin coat assembly. We will characterize the kinetics, stability and force generation by the clathrin lattice. This will be the first example of how enabling nanoscale imaging inside living cells will be a game changer in cell biology. It will open up a myriad of possibilities for the study of vesicular transport, viral and bacterial infection, nuclear pore transport, cell signalling and many more. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Condensed Matter Physics",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W611278037 | The Challenge of Safeguards in the WTO | The Challenge of Safeguards in the WTO provides a comprehensive overview of the safeguard mechanism in the multilateral trading system. It explains at length its historical and conceptual foundations and elaborates on the various requirements for the imposition of safeguards and the conduct of safeguard investigations. The author draws on his practical experience in order to analyse WTO case law as developed by WTO panels and the Appellate Body and to provide practical suggestions for the resolution of various complex issues which have arisen in practice. He also considers the challenges faced by companies involved in this type of case. | [
"Institutions, Governance and Legal Systems",
"Individuals, Markets and Organisations"
]
|
10.1103/PhysRevA.96.013406 | Efficient production of long-lived ultracold Sr2 molecules | We associate Sr atom pairs on sites of a Mott insulator optically and coherently into weakly bound ground-state molecules, achieving an efficiency above 80%. This efficiency is 2. 5 times higher than in our previous work [S. Stellmer, B. Pasquiou, R. Grimm, and F. Schreck, Phys. Rev. Lett. 109, 115302 (2012)PRLTAO0031-900710. 1103/PhysRevLett. 109. 115302] and obtained through two improvements. First, the lifetime of the molecules is increased beyond one minute by using an optical lattice wavelength that is further detuned from molecular transitions. Second, we compensate undesired dynamic light shifts that occur during the stimulated Raman adiabatic passage (STIRAP) used for molecule association. We also characterize and model STIRAP, providing insights into its limitations. Our work shows that significant molecule association efficiencies can be achieved even for atomic species or mixtures that lack Feshbach resonances suitable for magnetoassociation. | [
"Physical and Analytical Chemical Sciences",
"Fundamental Constituents of Matter"
]
|
10.1142/9789811207402_0028 | Search For New Physics Via Baryon Edm At Lhc | Permanent electric dipole moments (EDMs) of fundamental particles provide powerful probes for physics beyond the Standard Model. We propose to search for the EDM of strange and charm baryons at LHC, extending the ongoing experimental program on the neutron, muon, atoms, molecules and light nuclei. The EDM of strange $Λ$ baryons, selected from weak decays of charm baryons produced in $pp$ collisions at LHC, can be determined by studying the spin precession in the magnetic field of the detector tracking system. A test of $CPT$ symmetry can be performed by measuring the magnetic dipole moment of $Λ$ and $\overline{Λ}$ baryons. For short-lived $Λ_{c}^{+}$ and $Ξ_{c}^{+}$ baryons, to be produced in a fixed-target experiment using the 7 TeV LHC beam and channeled in a bent crystal, the spin precession is induced by the intense electromagnetic field between crystal atomic planes. The experimental layout based on the LHCb detector and the expected sensitivities in the coming years are discussed. | [
"Fundamental Constituents of Matter"
]
|
10.1088/1742-6596/473/1/012022 | Performance Of Simulated Annealing In P Spin Glasses | We perform careful numerical simulations of slow Monte-Carlo annealings in the dense 3-body spin glass model and compare with the predictions from different theories: thresholds states, isocomplexity, following state. We conclude that while isocomplexity and following state both provide excellent agreement the numerical data, the influence of threshold states – that is still the most commonly considered theory – can be excluded from our data. | [
"Condensed Matter Physics",
"Computer Science and Informatics"
]
|
10.1088/1741-2552/14/1/014001 | Extracellular Matrix Proteins As Temporary Coating For Thin Film Neural Implants | Objective. This study investigates the suitability of a thin sheet of extracellular matrix (ECM) proteins as a resorbable coating for temporarily reinforcing fragile or ultra-low stiffness thin-film neural implants to be placed on the brain, i. e. microelectrocorticographic (µECOG) implants. Approach. Thin-film polyimide-based electrode arrays were fabricated using lithographic methods. ECM was harvested from porcine tissue by a decellularization method and coated around the arrays. Mechanical tests and an in vivo experiment on rats were conducted, followed by a histological tissue study combined with a statistical equivalence test (confidence interval approach, 0. 05 significance level) to compare the test group with an uncoated control group. Main results. After 3 months, no significant damage was found based on GFAP and NeuN staining of the relevant brain areas. Significance. The study shows that ECM sheets are a suitable temporary coating for thin µECOG neural implants. | [
"Materials Engineering",
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1103/PhysRevB.84.104527 | Decoherence, Autler-Townes effect, and dark states in two-tone driving of a three-level superconducting system | We present a detailed theoretical analysis of a multilevel quantum system coupled to two radiation fields and subject to decoherence. We concentrate on an effect known from quantum optics as Autler-Townes splitting, which has been recently demonstrated experimentally in a superconducting phase qubit. In the three-level approximation, we derive analytical solutions and describe how they can be used to extract the decoherence rates and to account for the measurement data. Better agreement with the experiment can be obtained by extending this model to five levels. Finally, we investigate the stationary states created in the experiment and show that their structure is close to that of dark states. | [
"Condensed Matter Physics",
"Fundamental Constituents of Matter"
]
|
10.1038/mi.2014.70 | CCR2 + CD103 - Intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells | The identification of intestinal macrophages (ms) and dendritic cells (DCs) is a matter of intense debate. Although CD103 + mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103 - MPs remain controversial. We show here that intestinal CD103 - CD11b + MPs can be separated clearly into DCs and ms based on phenotype, gene profile, and kinetics. CD64 - CD103 - CD11b + MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C hi monocytes. Surprisingly, a significant proportion of these CD103 - CD11b + DCs express CCR2 and there is a selective decrease in CD103 - CD11b + DCs in mice lacking this chemokine receptor. CCR2 + CD103 - DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2 + DCs that is involved in priming mucosal T helper type 17 (Th17) responses. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W1549972920 | Route selection algorithm for Blind pedestrian | The vast majority of existing route selection processes is designed for vehicle navigation. In this paper we describe an adapted routing algorithm for visually impaired pedestrians based on users needs. Our aim was to find the most adapted route that connects origin and destination points, and which can provide the Blind with a sparse but helpful mental representation of the itinerary and surroundings. Based on multiple brainstorming sessions and interviews with blind people and an orientation and mobility (O&M) instructor, different classes of objects were defined and tagged in the Geographical Information System. The optimal route was then selected using the Dijkstra algorithm. This method will be used in NAVIG (Navigation Assisted by Artificial VIsion and GNSS), an assistive device for the Blind, whose aim is to improve orientation, mobility and objects localization. | [
"Computer Science and Informatics",
"Systems and Communication Engineering",
"Human Mobility, Environment, and Space"
]
|
W1974278211 | Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+AT (Slc7a9) in mice | Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b 0,+ AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b 0,+ . No remarkable gene expression changes were observed in other amino acid transporters and the peptide transporters in the intestine and kidney. Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout animals compared with wild-type animals. The fractional excretion of arginine was increased as expected (∼100%), but fractional excretions of lysine (∼35%), ornithine (∼16%), and cystine (∼11%) were less affected. Loss of function of b 0,+ AT reduced transport of cystine and arginine in renal BBMVs and completely abolished the exchanger activity of dibasic amino acids with neutral amino acids. In conclusion, loss of Slc7a9 function decreases the GFR and increases the excretion of several amino acids to a lesser extent than expected with no clear regulation at the mRNA and protein level of alternative transporters and no increased renal epithelial uptake. These observations indicate that transporters located in distal segments of the kidney and/or metabolic pathways may partially compensate for Slc7a9 loss of function. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
]
|
10.1038/srep19676 | Magnetism and exchange interaction of small rare-earth clusters; Tb as a representative | Here we follow, both experimentally and theoretically, the development of magnetism in Tb clusters from the atomic limit, adding one atom at a time. The exchange interaction is, surprisingly, observed to drastically increase compared to that of bulk, and to exhibit irregular oscillations as a function of the interatomic distance. From electronic structure theory we find that the theoretical magnetic moments oscillate with cluster size in exact agreement with experimental data. Unlike the bulk, the oscillation is not caused by the RKKY mechanism. Instead, the inter-atomic exchange is shown to be driven by a competition between wave-function overlap of the 5d shell and the on-site exchange interaction, which leads to a competition between ferromagnetic double-exchange and antiferromagnetic super-exchange. This understanding opens up new ways to tune the magnetic properties of rare-earth based magnets with nano-sized building blocks. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
]
|
2725253 | Human uterus cell atlas | The Human Uterus Cell Atlas (HUTER) project aims to create the single-cell and spatial reference map of the human uterus. HUTER project will provide unprecedented insight at transcriptomic, genomic and spatial changes of this important female organ not only throughout the menstrual cycle but also across lifespan.
The human uterus is a flagship reproductive organ with profound implications not only in reproduction but also in women´s health. HUTER can advance the Human Cell Atlas initiative for the exploitation potential in Obstetrics and Gynaecology and biomedicine research areas such as Regenerative Medicine or Reproductive Medicine. The uterus is itself a model for regenerative medicine since (i) endometrial tissue regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types, and (ii) myometrial tissue has remarkable regenerative capacity and extensive remodelling throughout pregnancy.
Hence, the primary motivation HUTER proposal stems from the need to better understand the human uterus in order to more effectively address uterine diseases that impact women´s health such as myomas or endometriosis and/or might contribute to infertility, infant and maternal mortality and morbidity. HUTER technological and biological platform will be a crucial resource for the scientific and clinical communities to define the cellular basis of health and disease, allowing the rapid development of new diagnosis and prognosis tools and therapeutic advancements in the field. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
]
|
W44444153 | Application of MoS2 based cutting fluids in minimum quantity lubrication during machining of stainless steel AISI 316 | Last decade witnessed rapid increase in development of advanced materials for high performance applications. While these materials solve a great deal of technological issue, they also pose considerable challenge in machining due to poor machinability characteristics. Many strategies have been devised. However, environmental friendly machining techniques have been given major emphasis and minimum quantity lubrication (MQL) technique is one of them. Although molybdenum disulfide (MoS2) is widely regarded as solid lubricant material, its potential as an effective medium in MQL particularly in turning operation is yet to be explored. During the current research work, the effect of addition of MoS2 powder, with average size of around 1 µm, in two different base fluids namely conventional water soluble oil and paraffin oil (a mineral oil) has been investigated during turning of AISI 316L grade austenitic stainless steel with the help response surface methodology (RSM)-based design of experiment. The results clearly indicated the beneficial aspects of MoS2 in reducing the cutting temperature by virtue of enhanced heat transfer characteristics of micro-particle of MoS2.The same powder also helped in bringing down cutting force and chip thickness while improving surface finish. It was observed that MoS2-mixed conventional cutting fluid demonstrated superior machining characteristics. Further attempt was also made to determine optimal cutting condition using grey relational analysis (GRA)-based multi objective optimization technique. The study, therefore, clearly established promising potential of MoS2 powder to be mixed with suitable base fluid under MQL environment during machining AISI 316L grade austenitic stainless steel. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
10.1016/j.bbabio.2017.11.001 | Identification of protein W, the elusive sixth subunit of the Rhodopseudomonas palustris reaction center-light harvesting 1 core complex | The X-ray crystal structure of the Rhodopseudomonas (Rps. ) palustris reaction center-light harvesting 1 (RC-LH1) core complex revealed the presence of a sixth protein component, variably referred to in the literature as helix W, subunit W or protein W. The position of this protein prevents closure of the LH1 ring, possibly to allow diffusion of ubiquinone/ubiquinol between the RC and the cytochrome bc1 complex in analogous fashion to the well-studied PufX protein from Rhodobacter sphaeroides. The identity and function of helix W have remained unknown for over 13 years; here we use a combination of biochemistry, mass spectrometry, molecular genetics and electron microscopy to identify this protein as RPA4402 in Rps. palustris CGA009. Protein W shares key conserved sequence features with PufX homologs, and although a deletion mutant was able to grow under photosynthetic conditions with no discernible phenotype, we show that a tagged version of protein W pulls down the RC-LH1 complex. Protein W is not encoded in the photosynthesis gene cluster and our data indicate that only approximately 10% of wild-type Rps. palustris core complexes contain this non-essential subunit; functional and evolutionary consequences of this observation are discussed. The ability to purify uniform RC-LH1 and RC-LH1-protein W preparations will also be beneficial for future structural studies of these bacterial core complexes. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1038/s41467-018-03677-z | Structural rearrangements of the histone octamer translocate DNA | Nucleosomes, the basic unit of chromatin, package and regulate expression of eukaryotic genomes. Nucleosomes are highly dynamic and are remodeled with the help of ATP-dependent remodeling factors. Yet, the mechanism of DNA translocation around the histone octamer is poorly understood. In this study, we present several nucleosome structures showing histone proteins and DNA in different organizational states. We observe that the histone octamer undergoes conformational changes that distort the overall nucleosome structure. As such, rearrangements in the histone core α-helices and DNA induce strain that distorts and moves DNA at SHL 2. Distortion of the nucleosome structure detaches histone α-helices from the DNA, leading to their rearrangement and DNA translocation. Biochemical assays show that cross-linked histone octamers are immobilized on DNA, indicating that structural changes in the octamer move DNA. This intrinsic plasticity of the nucleosome is exploited by chromatin remodelers and might be used by other chromatin machineries. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1007/s00216-016-9431-1 | Site-specific quantification of lysine acetylation in the N-terminal tail of histone H4 using a double-labelling, targeted UHPLC MS/MS approach | We developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the site-specific quantification of lysine acetylation in the N-terminal region of histone H4 by combining chemical derivatization at the protein and peptide levels with digestion using chymotrypsin and trypsin. Unmodified ε-amino groups were first modified with propionic acid anhydride and the derivatized protein digested with trypsin and chymotrypsin. The newly formed peptide N-termini were subjected to a second derivatization step with d6- (heavy) or d0- (light) acetic acid anhydride. Samples were mixed at different ratios and peptides monitored by multiple reaction monitoring (MRM) LC-MS/MS. The method was validated in terms of linearity (R2 ≥ 0. 94), precision (RSD ≤ 10 %), and accuracy (≤27 %) and used to assess the effect of the histone deacetylase (HDAC) inhibitors SAHA and MS-275 in the murine macrophage-like cell line RAW 264. 7. SAHA and MS-275 showed site-specific effects on the acetylation levels of K5 and K8 with the K5(Ac)–K8 and K5–K8(Ac) peptides increasing 2. 5-fold and 5-fold upon treatment with SAHA and MS-275, respectively. Assessing lysine acetylation in a site-specific manner is important for gaining a better understanding of the effects of HDAC inhibitors and for clarifying disease mechanisms where lysine acetylation plays a role. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
171419 | Infrared structural monitoring of cracks using thermoelastic analysis in production environments | This proposal is built around a well-established set of laboratory-based techniques, which use Thermoelastic Stress Analysis (TSA) for characterising strain fields associated with structural features. It is proposed to extend their applicability to aircraft structure tests and to enhance their productivity through the use of automation for data acquisition and processing in an industrial environment. Thermoelastic stress analysis is well-established as a laboratory-based technique and its use for structural analysis , fracture mechanics and damage mechanics has been explored extensively. Most of the work so far has been performed using relatively small test coupons with simple structural features. In the proposed work the aim is to prove the feasibility of applying thermoelastic stress analysis in a structural test environment for detecting stress hotspots. The structural test tools developed will enable fast acquisition of data-rich stress fields in large aerospace components during structural tests at relatively low cost and the post-processing capabilities will allow meaningful comparison of experimental results with those from computational models and service life evaluations. The scientific and technical objectives are designed to lead to innovative methodologies that will enable more detailed stress information to be acquired during aircraft structure tests. These methodologies will be faster, lower cost and provide higher confidence in computational models than is possible at the moment. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
230290 | Social capital and enforcement of informal contracts in developing economies | In the absence of formal contracts and sanctioning agencies, many economic exchanges are based on informal arrangements that cannot be enforced through courts or monitored by external parties. In this project, we study the role of social capital in generating social sanctions that agents can use to enforce informal arrangements. Typically, in the literature, social sanctions are posited parametrically, and are supposed to be used unilaterally whenever there is a breach in the contract . They are thus conceived essentially as an instrument to sustain existing agreements. This argument however relies on unduly restrictive assumptions on the nature and the use of social sanctions: they are costless and they can be used only against defecting members. We intend to go beyond the literature by properly modelling what constitutes a social sanction, so as to provide stronger micro-foundations to this concept. We therefore intend to first investigate the mechanisms through which social capital, in the sense of dense interdependence between agents, generates social sanctions. In a second step, we will explore the impact of social sanctions in sustaining existing agreements, allowing sanctions to be used to force agents to renege on their obligations if such defection is beneficial to their particular group. To give an example, in the context of micro-credit, group members can use social sanctions to enforce repayment of the loan to the bank but, with appropriate norms and beliefs, they can also use the same sanctions to enforce collective default against the lending agency. At the theoretical level, we will explore the role of social sanctions in micro-credit groups, in collective action problems and in informal insurance arrangements. We shall also carry out two empirical projects based on original data sets: one on the evolution of microfinance groups in India, and the other on social sanctions and pressures for interpersonal redistribution in Cameroon. | [
"The Social World and Its Interactions",
"Individuals, Markets and Organisations"
]
|
3739108 | Unlocking self-patterning competence to engineer 3d human spinal cord | Organizers direct formation of the body, releasing morphogens to position tissues and organs. But what organizes the organizers? I aim to harness organizer formation to build self-patterning 3D human spinal cord in vitro.
In developing spinal cord, the floorplate organizer secretes Sonic Hedgehog to direct ventral-dorsal patterning. Prof Tanaka (secondment) discovered how to recapitulate this in vitro: single mouse naïve pluripotent stem cells (PSCs) form neural tube organoids and an early pulse of retinoic acid prompts self-organization of floorplate that drives patterning as in vivo. However, attempts to form cognate human organoids have been unsuccessful. There is a restricted window of competence to initiate floorplate formation, which conventional primed human PSCs are unable to access.
To overcome this, I will combine microenvironment bioengineering with new naïve human iPSCs (Prof Elvassore, host) to recapitulate and study human development from an earlier stage, gaining access to molecular events that may underpin later fate specification and tissue organization. By mechanistic analysis in mouse organoids, I will reveal how competence is instated, how it is closed, and how to prolong or re-instate competence de novo. This knowledge will guide me in unlocking the competent state for human PSCs in vitro, and has implications for activating spinal cord regeneration in vivo. By use of sophisticated engineering technologies pioneered in the Elvassore group, I will control the micro-environment to guide tissue growth and formation, mimicking natural physiology and ensuring reproducibility. By engineering 3D organized human spinal cord in vitro, this project will bridge basic knowledge of critical and inaccessible stages of human development with future biomedical applications. This interdisciplinary training opportunity will build on my doctoral expertise in PSC identity transitions, setting me apart with a strong independent niche for my future career. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Biotechnology and Biosystems Engineering"
]
|
10.1016/j.concog.2009.12.018 | Optimizing subjective measures of consciousness | Dienes and Seth (2010) conclude that confidence ratings and post-decision wagering are two comparable and recommendable measures of conscious experience. In a recently submitted paper, we have however found that both methods are problematic and seem less suited to measure consciousness than a direct introspective measure. Here, we discuss the methodology and conclusions put forward by Dienes and Seth, and why we think the two experiments end up with so different recommendations. | [
"The Human Mind and Its Complexity"
]
|
10.1016/j.cell.2007.11.034 | RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA | MicroRNAs (miRNAs) are inhibitors of gene expression capable of controlling processes in normal development and cancer. In mammals, miRNAs use a seed sequence of 6-8 nucleotides (nt) to associate with 3′ untranslated regions (3′UTRs) of mRNAs and inhibit their expression. Intriguingly, occasionally not only the miRNA-targeting site but also sequences in its vicinity are highly conserved throughout evolution. We therefore hypothesized that conserved regions in mRNAs may serve as docking platforms for modulators of miRNA activity. Here we demonstrate that the expression of dead end 1 (Dnd1), an evolutionary conserved RNA-binding protein (RBP), counteracts the function of several miRNAs in human cells and in primordial germ cells of zebrafish by binding mRNAs and prohibiting miRNAs from associating with their target sites. These effects of Dnd1 are mediated through uridine-rich regions present in the miRNA-targeted mRNAs. Thus, our data unravel a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
W2026728239 | The effects of commitment and identification on consumption | Previous work has demonstrated relationships among consumers' perceptions of a service organization's characteristics, their affiliation history with the organization, their consumption of the organization's products and services, and their identification with the organization. Other work has examined similar sets of variables, but using commitment in lieu of identification. This study uses structural equation modeling to test whether affiliation characteristics and perceptions of the organization affect consumption, and whether identification and commitment mediate the effect. The rival hypothesis that consumption affects identification is also tested. The pathway from organizational characteristics to consumption is found to be mediated by commitment and identification. Affiliation characteristics have a direct effect on consumption. | [
"Individuals, Markets and Organisations",
"The Social World and Its Interactions"
]
|
10.1016/j.geomphys.2015.04.006 | On the number of connected components of random algebraic hypersurfaces | We study the expectation of the number of components b<inf>0</inf>(X) of a random algebraic hypersurface X defined by the zero set in projective space RPn of a random homogeneous polynomial f of degree d. Specifically, we consider invariant ensembles, that is Gaussian ensembles of polynomials that are invariant under an orthogonal change of variables. Fixing n, under some rescaling assumptions on the family of ensembles (as d→. ∞), we prove that Eb0(X) has the same order of growth as [Eb0(X∩RP1)]n. This relates the average number of components of X to the classical problem of M. Kac (1943) on the number of zeros of the random univariate polynomial f|RP1. The proof requires an upper bound for Eb0(X), which we obtain by counting extrema using Random Matrix Theory methods from Fyodorov (2013), and it also requires a lower bound, which we obtain by a modification of the barrier method from Lerario and Lundberg (2015) and Nazarov and Sodin (2009). We also provide quantitative upper bounds on implied constants; for the real Fubini-Study model these estimates provide super-exponential decay (as n→. ∞) of the leading coefficient (in d) of Eb0(X). | [
"Mathematics"
]
|
W2058209443 | Statistics and analysis of service availability in cloud computing | This paper focuses on solving the problem of measuring and monitoring service availability in Cloud Computing. It introduces existing Service-Level Agreement (SLA) monitoring approaches and frameworks. On this basis, it presents a new approach which monitors cloud service availability from the client-centric point of view. This approach was designed, implemented and tested on a sample cloud environment. The measured data is statistically analyzed to obtain results which are as accurate as possible. The entire process of monitoring and statistical analysis is automated so that it can be incorporated in further research to create a complete solution for managing SLA in Cloud Computing from a client-centric perspective. | [
"Computer Science and Informatics",
"Systems and Communication Engineering",
"Mathematics"
]
|
10.1016/j.cub.2016.12.052 | A Functional Gradient in the Rodent Prefrontal Cortex Supports Behavioral Inhibition | The ability to plan and execute appropriately timed responses to external stimuli is based on a well-orchestrated balance between movement initiation and inhibition. In impulse control disorders involving the prefrontal cortex (PFC) [1], this balance is disturbed, emphasizing the critical role that PFC plays in appropriately timing actions [2–4]. Here, we employed optogenetic and electrophysiological techniques to systematically analyze the functional role of five key subareas of the rat medial PFC (mPFC) and orbitofrontal cortex (OFC) in action control [5–9]. Inactivation of mPFC subareas induced drastic changes in performance, namely an increase (prelimbic cortex, PL) or decrease (infralimbic cortex, IL) of premature responses. Additionally, electrophysiology revealed a significant decrease in neuronal activity of a PL subpopulation prior to premature responses. In contrast, inhibition of OFC subareas (mainly the ventral OFC, i. e. , VO) significantly impaired the ability to respond rapidly after external cues. Consistent with these findings, mPFC activity during response preparation predicted trial outcomes and reaction times significantly better than OFC activity. These data support the concept of opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive movement control. By attributing defined roles to rodent PFC sections, this study contributes to a deeper understanding of the functional heterogeneity of this brain area and thus may guide medically relevant studies of PFC-associated impulse control disorders in this animal model for neural disorders [10–12]. | [
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
Q2715853 | Sovvenzione di capitale circolante per SERVICE Iwona Zdańska — 15418 | Il progetto è volto a sostenere l'impresa nel fornire liquidità e nel sostenere le sue operazioni quotidiane a causa delle difficoltà finanziarie che si sono verificate nella società a causa dell'epidemia di COVID-19. Assistenza finanziaria fornita sulla base del regime SA.57015. | [
"Individuals, Markets and Organisations"
]
|
10.1038/ncomms12101 | Frizzled 7 and PIP 2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling | PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP 2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co-operative binding of the tripartite complex and identify residues crucial for membrane PIP 2 -specific recognition. Experiments with cells support the importance of the syntenin-PIP 2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1051/0004-6361/201832718 | Sensitivity Of Gravito Inertial Modes To Differential Rotation In Intermediate Mass Main Sequence Stars | Context. While rotation has a major impact on stellar structure and evolution, its effects are not well understood. Thanks to high-quality and long-time base photometric observations obtained with recent space missions, we are now able to study stellar rotation more precisely. Aims. We aim to constrain radial differential rotation profiles in γ Doradus (γ Dor) stars, and to develop new theoretical seismic diagnosis for such stars with rapid and potentially non-uniform rotation. Methods. We have derived a new asymptotic description which accounts for the impact of weak differential near-core rotation on gravity-mode period spacings. The theoretical predictions are illustrated from pulsation computations with the code GYRE and compared with observations of γ Dor stars. When possible, we also derived the surface rotation rates in these stars by detecting and analysing signatures of rotational modulation, and computed the core-to-surface rotation ratios. Results. Stellar rotation must be strongly differential before its effects on period spacing patterns can be detected, unless multiple period spacing patterns can be compared. Six stars in our sample exhibit a single unexplained period spacing pattern of retrograde modes. We hypothesise that these are Yanai modes. Finally, we find signatures of rotational spot modulation in the photometric data of eight targets. Conclusions. If only one period spacing pattern is detected and analysed for a star, it is difficult to detect differential rotation. A rigidly rotating model will often provide the best solution. Differential rotation can only be detected when multiple period spacing patterns have been found for a single star or its surface rotation rate is known as well. This is the case for eight of the stars in our sample, revealing surface-to-core rotation ratios between 0. 95 and 1. 05. | [
"Universe Sciences"
]
|
802701 | Engineering and exploring anyonic quantum gases | This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms. | [
"Condensed Matter Physics",
"Fundamental Constituents of Matter"
]
|
2731322 | Solar twinning to create solar research twins | Research and Innovation (R&I) in Concentrating Solar Thermal (CST) technologies promises global impacts through new and sustainable solutions to societal challenges. CST technologies include 1) Solar Thermal Electricity (STE/CSP), 2) Solar Heat for Industrial Processes (SHIP), 3) Solar Fuels, and 4) Clean and Fresh Water. Europe is currently a global technology leader in CST, and SolarTwins is designed to strengthen this leadership position. The Goal of SolarTwins is to Step-Up the Scientific Excellence and Innovation Capacity of the Promising Institution METU-GÜNAM's CST research laboratory through Twinning with the Leading Institutions PSA-CIEMAT and DLR. SolarTwins builds on several EU CST R&I networks and activities in which all 3 institutions are participating including EU-SOLARIS, EERA-JP-CSP, and SFERA-III. SolarTwins contains 3 Twinning Work Packages (WPs 1-3). WP1 contains cross-cutting activities including Joint Kick-Off Activities targeting stakeholders and External Training to strengthen local, regional and national R&I capacities. WP2 is dedicated to ESRs and contains 2 summer schools at METU taught be experts from PSA-CIEMAT and DLR, and exchange of METU ESRs to PSA-CIEMAT and DLR for training and research mentoring. WP3 is dedicated to developing joint research lines between METU-GÜNAM and each of PSA-CIEMAT and DLR. WP3 includes activities for METU-GÜNAM personnel at each of PSA-CIEMAT and DLR to formulate joint research lines, and METU-GÜNAM staff exchange to each of PSA-CIEMAT and DLR to develop joint research proposals. WP4 is dedicated to maximising the Impacts of SolarTwins and includes Exploitation, Dissemination, and Communication tasks, and a Final Conference. WP5 is dedicated to project management. SolarTwins is specifically formulated to lead to Joint Research Proposals that target large joint funding opportunities to increase competitive research funds to all partners, and result in more effective use of public research funds. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
US US2005028716 | PHARMACEUTICAL COMPOSITION AND METHOD FOR TREATING NEURODEGENERATIVE DISORDERS | The invention provides compositions and methods for treating neurodegenerative disorders. The method of the invention involves administering to an individual in need of treatment a composition an acetylcholine esterase inhibitor in combination with another therapeutic agent. The methods and compositions of the invention are useful for treating and preventing neurodegenerative disorders like Alzheimer's disease, dementia, and mild cognitive impairment. | [
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1038/srep42563 | Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells | We have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin's effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding proteins that are known to interact with apigenin, which identified C1QTNF2, encoding for Complement C1q tumor necrosis factor-related protein 2, a secreted adipocytokine with metabolic effects in liver. To validate its disease relevance, C1QTNF2 expression is reduced during hepatic stellate cell activation in culture and in a mouse model of alcoholic liver injury in vivo, and its expression correlates with better clinical outcomes in patients with hepatitis C cirrhosis (n = 216), suggesting it may have a protective role in cirrhosis progression. These findings reinforce the value of computational approaches to drug discovery for hepatic fibrosis, and identify C1QTNF2 as a potential mediator of apigenin's anti-fibrotic activity. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
]
|
10.1007/jhep03(2019)060 | Resummation for rapidity distributions in top-quark pair production | Abstract
We extend our framework for the simultaneous resummation of soft and small-mass logarithms to rapidity distributions in top quark pair production. We give numerical results for the rapidity distribution of the top quark or the anti-top quark, as well as the rapidity distribution of the
$$ t\overline{t} $$
t
t
¯
pair, finding that resummation effects stabilize the dependence of the differential cross sections on the choice of factorization scale. We compare our results with recent measurements at the Large Hadron Collider and find good agreement. Our results may be useful in the extraction of the gluon parton distribution function from
$$ t\overline{t} $$
t
t
¯
production. | [
"Fundamental Constituents of Matter"
]
|
10.1073/pnas.1304168111 | Four-dimensional live imaging of apical biosynthetic trafficking reveals a post-Golgi sorting role of apical endosomal intermediates | Emerging data suggest that in polarized epithelial cells newly synthesized apical and basolateral plasma membrane proteins traffic through different endosomal compartments en route to the respective cell surface. However, direct evidence for trans-endosomal pathways of plasma membrane proteins is still missing and the mechanisms involved are poorly understood. Here, we imaged the entire biosynthetic route of rhodopsin-GFP, an apical marker in epithelial cells, synchronized through recombinant conditional aggregation domains, in live Madin-Darby canine kidney cells using spinning disk confocal microscopy. Our experiments directly demonstrate that rhodopsin-GFP traffics through apical recycling endosomes (AREs) that bear the small GTPase Rab11a before arriving at the apical membrane. Expression of dominant-negative Rab11a drastically reduced apical delivery of rhodopsin-GFP and caused its missorting to the basolateral membrane. Surprisingly, functional inhibition of dynamin-2 trapped rhodopsin-GFP at AREs and caused aberrant accumulation of coated vesicles on AREs, suggesting a previously unrecognized role for dynamin-2 in the scission of apical carrier vesicles from AREs. A second set of experiments, using a unique method to carry out total internal reflection fluorescence microscopy (TIRFM) from the apical side, allowed us to visualize the fusion of rhodopsin-GFP carrier vesicles, which occurred randomly all over the apical plasma membrane. Furthermore, two-color TIRFM showed that Rab11a-mCherry was present in rhodopsin-GFP carrier vesicles and was rapidly released upon fusion onset. Our results provide direct evidence for a role of AREs as a post-Golgi sorting hub in the biosynthetic route of polarized epithelia, with Rab11a regulating cargo sorting at AREs and carrier vesicle docking at the apical membrane. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1073/pnas.1811874115 | Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex | Autophagy is an enigmatic cellular process in which double-membrane compartments, called “autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for delivery to lysosomes. Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER–phagophore junction. We combined single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, and biochemical analyses to characterize human ATG2A in complex with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge neighboring vesicles through interactions at each of its tips. WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex mediates ER–phagophore association and/or tethers vesicles to the ER–phagophore junction, establishing the required organization for phagophore expansion via the transfer of lipid membranes from the ER and/or the vesicles to the phagophore. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
851255 | Air Transport as Information and Computation | Air transport has by and large been studied as a transportation process, in which different elements, e.g. aircraft or passengers, move within the system. While intuitive, this approach entails several drawbacks, including the need for large-scale simulations, the reliance on real data, and the difficulty of extracting macro-scale conclusions from large quantities of micro- scale results. The lack of a better approach is in part responsible for our inability to fully understand delay propagation, one of the most important phenomena in air transport. ARCTIC proposes an ambitious program to change the conceptual framework used to analyse air transport, inspired by the way the brain is studied in neuroscience. It is based on understanding air transport as an information processing system, in which the movement of aircraft is merely a vehicle for information transfer. Airports then become computational units, receiving information from their neighbours through inbound flights under the form of delays; processing it in a potentially non-linear way; and redistributing the result to the system as outbound delays. In this proposal I show how, as already common in neuroscience, such computation can be made explicit by using a combination of information sciences and statistical physics techniques: from the detection of information movements through causality metrics, up to the representation of the resulting transfer structures through complex networks and their topological properties. The approach also entails important challenges, e.g. the definition of appropriate metrics or the translation of the obtained insights into implementable policies. In the main text of the proposal I present a number of preliminary results that point towards a radically new way of thinking about the dynamics of air transport. ARCTIC’s methodology will be used over the next five years to characterize and model delay propagation, as well as to limit its societal and economic impact. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1177/0271678X16675182 | Nogo A Regulates Vascular Network Architecture In The Postnatal Brain | Recently, we discovered a new role for the well-known axonal growth inhibitory molecule Nogo-A as a negative regulator of angiogenesis in the developing central nervous system. However, how Nogo-A affected the three-dimensional (3D) central nervous system (CNS) vascular network architecture remained unknown. Here, using vascular corrosion casting, hierarchical, synchrotron radiation μCT-based network imaging and computer-aided network analysis, we found that genetic ablation of Nogo-A significantly increased the three-dimensional vascular volume fraction in the postnatal day 10 (P10) mouse brain. More detailed analysis of the cerebral cortex revealed that this effect was mainly due to an increased number of capillaries and capillary branchpoints. Interestingly, other vascular parameters such as vessel diameter, -length, -tortuosity, and -volume were comparable between both genotypes for non-capillary vessels and capillaries. Taken together, our three-dimensional data showing more vessel segments and branchpoints at unchanged vessel morphology suggest that stimulated angiogenesis upon Nogo-A gene deletion results in the insertion of complete capillary micro-networks and not just single vessels into existing vascular networks. These findings significantly enhance our understanding of how angiogenesis, vascular remodeling, and three-dimensional vessel network architecture are regulated during central nervous system development. Nogo-A may therefore be a potential novel target for angiogenesis-dependent central nervous system pathologies such as brain tumors or stroke. | [
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2897189032 | Charge compensation and capacity fading in LiCoO <sub>2</sub> at high voltage investigated by soft x-ray absorption spectroscopy | In order to obtain an in-depth insight into the mechanism of charge compensation and capacity fading in LiCoO2, the evolution of electronic structure of LiCoO2 at different cutoff voltages and after different cycles are studied by soft x-ray absorption spectroscopy in total electron (TEY) and fluorescence (TFY) detection modes, which provide surface and bulk information, respectively. The spectra of Co L2,3-edge indicate that Co contributes to charge compensation below 4.4 V. Combining with the spectra of O K-edge, it manifests that only O contributes to electron compensation above 4.4 V with the formation of local O 2p holes both on the surface and in the bulk, where the surficial O evolves more remarkably. The evolution of the O 2p holes gives an explanation to the origin of or even O2. A comparison between the TEY and TFY of O K-edge spectra of LiCoO2 cycled in a range from 3 V to 4.6 V indicates both the structural change in the bulk and aggregation of lithium salts on the electrode surface are responsible for the capacity fading. However, the latter is found to play a more important role after many cycles. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
171844 | Flare likelihood and region eruption forecasting | Space weather can have detrimental, and in some cases catastrophic, effects upon a multitude of technologies on which we depend as part our daily lives. Adverse space weather is now known to result from solar flares and coronal mass ejections released from the turbulent and highly complex magnetic fields of active regions. Understanding how active region magnetic fields evolve and produce these events is therefore of fundamental importance to developing accurate and reliable space-weather monitoring and forecasting capabilities.
We therefore propose to develop an advanced flare prediction system (Flare Likelihood And Region Eruption Forecasting; FLARECAST) that is based on automatically extracted physical properties of active regions coupled with state-of-the-art flare prediction methods and validated using the most appropriate forecast verification measures.
Active region properties, such as area, magnetic flux, shear, magnetic complexity, helicity and proxies for magnetic energy, will be extracted from solar magnetogram and white-light images in near-realtime using advanced image-processing techniques. Once active region properties have been extracted, they will be correlated with solar flare activity and used to optimize prediction algorithms based on statistical, unsupervised clustering and supervised learning methods. This will enable us to validate our image processing and flare prediction algorithms before launching a near-realtime flare forecasting service, the first of its kind in the world.
FLARECAST will therefore form the basis of the first quantitative, physically motivated and autonomous active region monitoring and flare forecasting system, which will be of use to space-weather researchers and forecasters in Europe and around the globe. | [
"Universe Sciences",
"Computer Science and Informatics"
]
|
10.1016/j.tet.2014.05.027 | The influence of vicinal threo-difluorination on electro-optic and mesogenic properties of propyleneoxy-linked nematic liquid crystals | A protocol for the preparation of a series of liquid crystals is presented, where the structures carry a central propyleneoxy motif carrying two vicinal threo-C-F bonds. The negative dielectric anisotropy (-Δε) of the resultant liquid crystals has been explored. The stereoelectronic relationship between the vicinal C-F bonds was anticipated to orientate the fluorine atoms gauche to each other when the propylene chain is extended. This is shown to be the case. This orientation of the C-F bonds generates a net dipole perpendicular to the molecular axis, a prerequisite for the design of dielectrically negative liquid crystals. However the molecules adopt a conformation where one C-F bond reinforces the net molecular dipole, and the other has a counter effect, thus the introduction of the motif has an almost neutral effect on dielectric anisotropy (Δεvirt) of these candidate liquid crystals. However, introduction of the difluoro motif raises the melting points of the liquid crystals and increases their conformational rigidity. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
638899 | Researchers in the knowledge triangle | Since 2006, members of EURAXESS Bulgaria have organized 13 European Researchers Nights (ERN), and have attracted several new consortium members with different profiles - universities, research institutes, NGOs, entrepreneurs. Based on past experience, the main goal of Researchers in the Knowledge Triangle (K-TRIO 5) project is to bring researchers closer to society, attract young people to STEM and boost Citizens Science. The project will contribute for increasing the number of researchers in Bulgaria by making the society, and young people, aware of excellent European achievements in research and innovation (R&I), and of the Centers of Excellence (CoE) and Centers of Competence and their contribution to green, smart and sustainable regional development.
In 2020 the consortium made several steps for changing stereotypes and nurturing a new culture in R&I, and making young people aware of the multiple career paths of researchers (incl. MSC fellows), best-practice examples of researchers achievements, and research infrastructure in Bulgaria. Special emphasis will be made on European policy and on funding for R&I provided by EU RTD programs and Structural Funds.
With a large variety of pre-events, online activities and 2-days ERN events in many Bulgarian cities, the project will create greater understanding on how R&I contribute to well-being of people and sustainable development, and highlight the common European efforts for Green and Digital transformation, building Smart Cities, and taking full advantage of BIG Data, Artificial Intelligence and Cloud computing. With the involvement of all CoE UNITe partners, and their large network, in addition to EURAXESS Bulgaria, K-TRIO 5 will cover all Bulgarian regions. Forum Science will guide a professional science communication, and ensure greater visibility of project activities. | [
"The Social World and Its Interactions",
"Individuals, Markets and Organisations"
]
|
10.1177/1354066117745365 | International Misrecognition The Politics Of Humour And National Identity In Israel S Public Diplomacy | Recognition, or the lack of it, is a central concern in International Relations. However, how states cope with international misrecognition has so far not been thoroughly explored in International . . . | [
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems"
]
|
10.1016/j.tree.2013.01.019 | Pollinator-mediated evolution of floral signals | Because most plants rely on animals for pollination, insights from animal sensory ecology and behavior are essential for understanding the evolution of flowers. In this review, we compare and contrast three main types of pollinator responses to floral signals - receiver bias, 'adaptive' innate preferences, and associative learning - and discuss how they can shape selection on floral signals. We show that pollinator-mediated selection on floral signals can be strong and that the molecular bases of floral signal variation are often surprisingly simple. These new empirical and conceptual insights into pollinator-mediated evolution provide a framework for understanding patterns of both convergent (pollination syndromes) and advergent (floral mimicry) floral signal evolution. | [
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
219153 | Monitoring built-up area from satellite | Survey Lab is a spin off company of Sapienza University devoted to scientific and technological knowledge-transfer in order to capture additional business opportunities in the field of civil and environmental engineering. The company core business is the development and commercialization of innovative geomatic monitoring systems based on advanced surveying and mapping technologies. A specific focus is on the assimilation of remote sensing data obtained by Earth Observation satellite sensors into ground-based monitoring and modelling procedures. Survey lab has recently obtained a Grant from European Commission through the SME Instrument phase 2 in the topic Space with the project I.MODI.
Presently, the main business strategy of the company is to develop innovative value added services and products with a particular focus on Copernicus Earth Observation Programme. To reach this goal the company needs to strengthen its expertise on the development of advanced geostatistics tools that will be tailored to services that are currently still under development.
Therefore, a specialist with a solid background in geospatial data analysis and experience in software development is needed. To this day, Survey Lab hasn’t be able to the recruit a highly qualified specialist on Italian national job market, due to the lack of University Courses in this specific field. On the contrary there are many post-graduate, masters and phd courses active in other EU countries with solid experience in statistic and programming language (such as Geo-Information Science and Earth Observation University of Twente, Delft University of Technology, etc.).
We believe that the required expertise could lead to a significant growth of Survey Lab capability in the implementation of advanced numerical tools, necessary to improve the data analyses procedures. | [
"Earth System Science",
"Products and Processes Engineering",
"Computer Science and Informatics"
]
|
10.1038/s41578-018-0036-5 | Heusler, Weyl and Berry | Heusler compounds, initially discovered by Fritz Heusler more than a century ago, have grown into a family of more than 1,000 compounds, synthesized from combinations of more than 40 elements. Recently, by incorporating heavy elements that can give rise to strong spin–orbit coupling, non-trivial topological phases of matter, such as topological insulators, have been discovered in Heusler materials. Moreover, interplay between the symmetry, spin–orbit coupling and magnetic structure allows for the realization of a wide variety of topological phases through Berry curvature design. The topological properties of Heusler compounds can be manipulated by various external perturbations, resulting in exotic properties, such as the chiral anomaly and large anomalous, spin and topological Hall effects. In addition, the non-zero Berry curvature that arises as a result of non-collinear order gives rise to a non-zero anomalous Hall effect. Besides this k-space Berry curvature, Heusler compounds with non-collinear magnetic structures also possess real-space topological states in the form of magnetic antiskyrmions, which have not yet been observed in other materials. In this Review, we discuss Heusler compounds from a topological perspective and the connection between the topology and the symmetry properties, spin gapless semiconductors, magnetic compensated ferrimagnets, non-collinear order in ferromagnetic and antiferromagnetic Heusler compounds, the anomalous Hall effect and, finally, magnetic antiskyrmions. Together with the new topological viewpoint and the high tunability, novel physical properties and phenomena await discovery in Heusler compounds. | [
"Condensed Matter Physics",
"Synthetic Chemistry and Materials"
]
|
10.1007/s10955-018-1992-2 | Convergence and Efficiency of Adaptive Importance Sampling Techniques with Partial Biasing | We propose a new Monte Carlo method to efficiently sample a multimodal distribution (known up to a normalization constant). We consider a generalization of the discrete-time Self Healing Umbrella Sampling method, which can also be seen as a generalization of well-tempered metadynamics. The dynamics is based on an adaptive importance technique. The importance function relies on the weights (namely the relative probabilities) of disjoint sets which form a partition of the space. These weights are unknown but are learnt on the fly yielding an adaptive algorithm. In the context of computational statistical physics, the logarithm of these weights is, up to an additive constant, the free-energy, and the discrete valued function defining the partition is called the collective variable. The algorithm falls into the general class of Wang–Landau type methods, and is a generalization of the original Self Healing Umbrella Sampling method in two ways: (i) the updating strategy leads to a larger penalization strength of already visited sets in order to escape more quickly from metastable states, and (ii) the target distribution is biased using only a fraction of the free-energy, in order to increase the effective sample size and reduce the variance of importance sampling estimators. We prove the convergence of the algorithm and analyze numerically its efficiency on a toy example. | [
"Mathematics",
"Computer Science and Informatics",
"Physical and Analytical Chemical Sciences"
]
|
NO 8800014 W | DEVICE IN A BUILDING STRUCTURE | The present invention relates to a device in connection with building structures, especially for supporting structures which by their net weight or by varying loads are subjected to deformation. Especially in connection with large roof structures one is enfaced with the problem that deformations due to net weight or variable natural loads give rise to so large deformations that irregularities are created in relation to adjacent building elements, in first instance walls or larger gates, especially drive-gates for hangars, workshops, etc. These problems are alleviated by a device comprising one or more displacement means (7) which by global displacement of the roof supporting members (2) neutralize the sum of local deformations in the critical points of the structure, for example at the supporting rail (4) for drive-gates (5). Such displacement means can also be used for eliminating the horizontal displacement of said supporting members. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
338957 | Nonequilibrium phenomena at femtosecond/nanometer scale | Nanoscale objects like magnetic molecules and clusters, quantum dots, and graphene, bring us novel physical concepts. Recently, the temporal scale of the order of tens of femtoseconds (femtoscale) became available and new physical phenomena associated with this time scale, such as laser-induced electron and magnetic phase transitions, were discovered. The theoretical background for understanding this new physics is still rather poor. This temporal scale, like the spatial nanoscale is intermediate between micro- and macroworld making the standard approaches developed in micro- and macrophysics not suitable anymore. Essentially new theoretical ideas and methods are necessary for its description, especially in a combination with the spatial nanoscale. The aim of this project is to provide such a background via detailed studies of key problems, and open the way for new practical applications.
Based on a combination of analytical and computational theoretical approaches (most of them were suggested by us), we plan to study systematically time-dependent many-body phenomena at the femto/nano scale. We will develop a theory of nonequilibrium magnetic interactions and spin dynamics of nanosystems and apply it to molecular magnets and clusters at metal surfaces and at graphene. We will study the physics of graphene and “artificial graphene” (array of semiconducting quantum dots) in strongly time-dependent electric fields (laser-induced ultrafast dynamics).
This list covers the crucial problems in this new field (nonequilibrium spin dynamics, calculation of response functions crucial for pump-probe experiments, new physics in highly excited graphene and graphene-like systems) and the success of the project will represent a breakthrough in our understanding of the nanoworld, with very important perspectives for applications, namely, for the drastic miniaturization of basic elements and enhancing speed of basic operations in electronics. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Fundamental Constituents of Matter"
]
|
10.1002/mrm.24771 | Quantification and correction of respiration induced dynamic field map changes in fMRI using 3D single shot techniques | Purpose Respiration induced dynamic field map changes in the brain are quantified and the influence on the magnitude signal (physiological noise) is investigated. Dynamic off-resonance correction allows to reduce the signal fluctuations overlaying the blood oxygenation level dependent signal in T2*-weighted functional imaging. Theory and Methods A single-shot whole brain imaging technique with 100 ms temporal resolution was used to measure dynamic off-resonance maps that were calculated from the incremental changes of the image phase. These off-resonance maps are then used to dynamically update the off-resonance corrected reconstruction. Results A global resonance offset and a pronounced gradient in head-foot direction were identified as the main components of the change during a respiration cycle. On average, correction for these fluctuations decreases the magnitude fluctuations by around 30%. Conclusion Single shot 3D imaging allows for a robust quantification of dynamic off-resonance changes in the brain. Correction for these fluctuations removes the physiological noise component associated with dynamic point spread function changes. | [
"Neuroscience and Disorders of the Nervous System",
"Systems and Communication Engineering",
"Physical and Analytical Chemical Sciences"
]
|
W4226303153 | Serologic study of Bartonella sp. infection among human population of Southern Spain | The purpose of this study was to determine the prevalence of IgG antibodies against Bartonella sp. in a randomly selected sample from the population of the patients of North Sanitary District of Jaén.We used a commercially available immunofluorescent test (Focus-Technology IFA Bartonella quintana and B. henselae test).Six hundred five healthy individuals were divided by sex into three age groups. We detected that 13.55% and 11.07% subjects were IgG seropositive to B. henselae and B. quintana, respectively.Our data show that the prevalence of both Bartonella species in Andalusia (Southern Spain) is relatively high. No statistical difference in the seropositivity was observed among these groups. In both cases, the IgG antibody titers ranged from 1/128 to 1/512. | [
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
677952 | The Tibetan Army of the Dalai Lamas (1642-1959) | TibArmy proposes to undertake a study of a previously unresearched subject: the Tibetan army during the period of the Buddhist government of the Dalai Lamas, known as the Ganden Phodrang, from 1642 to 1959. This government was the heir to a robust military culture with long experience in the defence of Buddhism since the Tibetan Imperial Period (7th-9th centuries); however, from its inception it decided to rely on foreign armies for its protection. On the basis of two distinctive features of this period—the creation and maintenance of the first Tibetan standing army and the limited number of the troops compared to former times—the project will explore the enduring ambivalence of the Dalai Lamas’ government towards having its own army, as well as its reasons, consequences and expressions in discourse and practice.
The methodology follows a multifaceted approach towards the military in Tibet, by taking into considerations its social, economic, political, legal, religious and cultural aspects, and focussing on the multicultural and connected historical context of the Tibetan army’s evolution (foreign Mongol and Manchu armies stationed in Tibet, and the later adoption of British and Japanese military models). The research project, based on written and oral multilingual sources, is structured along 5 thematic axes:
1. A history of the army institution (17th-20th c.): social, economic and political aspects; 2. Interactions with the Sino-Manchu troops and other foreign influences on the Tibetan army; 3. Cultural and discursive aspects: integration of the army within the Buddhist frame; 4. Material culture and photographs: a visual history of the Army (with photograph exhibition); 5. A lexicon of military terminology.
By focussing on the links between Buddhism and the military in Tibet, TibArmy will achieve a clearer understanding of the links between State construction, religion and army, and will also shed light on the past and current geo-political situation in Asia. | [
"The Study of the Human Past",
"Studies of Cultures and Arts"
]
|
10.1073/pnas.1110682108 | Phytochrome-Interacting Factor 4 (PIF4) regulates auxin biosynthesis at high temperature | At high ambient temperature, plants display dramatic stem elongation in an adaptive response to heat. This response is mediated by elevated levels of the phytohormone auxin and requires auxin biosynthesis, signaling, and transport pathways. The mechanisms by which higher temperature results in greater auxin accumulation are unknown, however. A basic helix-loop-helix transcription factor, PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), is also required for hypocotyl elongation in response to high temperature. PIF4 also acts redundantly with its homolog, PIF5, to regulate diurnal growth rhythms and elongation responses to the threat of vegetative shade. PIF4 activity is reportedly limited in part by binding to both the basic helix-loop-helix protein LONG HYPOCOTYL IN FAR RED 1 and the DELLA family of growth-repressing proteins. Despite the importance of PIF4 in integrating multiple environmental signals, the mechanisms by which PIF4 controls growth are unknown. Here we demonstrate that PIF4 regulates levels of auxin and the expression of key auxin biosynthesis genes at high temperature. We also identify a family of SMALL AUXIN UP RNA (SAUR) genes that are expressed at high temperature in a PIF4-dependent manner and promote elongation growth. Taken together, our results demonstrate direct molecular links among PIF4, auxin, and elongation growth at high temperature. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
]
|
10.1016/j.jneumeth.2014.02.010 | AAV vector-mediated secretion of chondroitinase provides a sensitive tracer for axonal arborisations | As part of a project to express chondroitinase ABC (ChABC) in neurons of the central nervous system, we have inserted a modified ChABC gene into an adeno-associated viral (AAV) vector and injected it into the vibrissal motor cortex in adult rats to determine the extent and distribution of expression of the enzyme. A similar vector for expression of green fluorescent protein (GFP) was injected into the same location. For each vector, two versions with minor differences were used, giving similar results. After 4 weeks, the brains were stained to show GFP and products of chondroitinase digestion. Chondroitinase was widely expressed, and the AAV-ChABC and AAV-GFP vectors gave similar expression patterns in many respects, consistent with the known projections from the directly transduced neurons in vibrissal motor cortex and adjacent cingulate cortex. In addition, diffusion of vector to deeper neuronal populations led to labelling of remote projection fields which was much more extensive with AAV-ChABC than with AAV-GFP. The most notable of these populations are inferred to be neurons of cortical layer 6, projecting widely in the thalamus, and neurons of the anterior pole of the hippocampus, projecting through most of the hippocampus. We conclude that, whereas GFP does not label the thinnest axonal branches of some neuronal types, chondroitinase is efficiently secreted from these arborisations and enables their extent to be sensitively visualised. After 12 weeks, chondroitinase expression was undiminished. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2007320289 | Intracranial atherosclerotic disease associated with moyamoya collateral formation: histopathological findings | Atherosclerotic disease has been suspected as a cause of moyamoya disease in some patients but has not, to the authors' knowledge, been confirmed by pathological studies. The authors present the histopathological findings in a patient with moyamoya collateral formation associated with atherosclerotic occlusive disease of the distal internal carotid artery (ICA). Typical atheromatous changes were evident in the distal ICA and proximal middle cerebral artery. In addition, intimal thickening, fibrosis, and abnormal internal elastic lamina were present in these vessels. These findings are common in moyamoya but not in atherosclerotic disease. Proliferation and enlargement of the lenticulostriate arteries in the basal ganglia was also identified. Moyamoya phenomenon secondary to atherosclerotic disease has similar histopathological features to idiopathic moyamoya phenomenon, both in the affected large basal arteries and lenticulostriate collaterals. These findings support the hypothesis advanced by Peerless that moyamoya is a 2-step process involving an obliterative vasculopathy of the terminal ICA and a secondary proliferative response. | [
"Physiology in Health, Disease and Ageing",
"Neuroscience and Disorders of the Nervous System"
]
|
10.1016/j.jhevol.2013.09.010 | Nutritional values of tortoises relative to ungulates from the Middle Stone Age levels at Blombos Cave, South Africa: Implications for foraging and social behaviour | The site of Blombos Cave (BBC), Western Cape, South Africa has been a strong contributor to establishing the antiquity of important aspects of modern human behaviour, such as early symbolism and technological complexity. However, many linkages between Middle Stone Age (MSA) behaviour and the subsistence record remain to be investigated. Understanding the contribution of small fauna such as tortoises to the human diet is necessary for identifying shifts in overall foraging strategies as well as the collecting and processing behaviour of individuals unable to participate in large-game hunting. This study uses published data to estimate the number of calories present in tortoises as well as ungulates of different body size classes common at South African sites. A single tortoise (Chersina angulata) provides approximately 3332 kJ (796 kcal) of calories in its edible tissues, which is between 20 and 30% of the daily energetic requirements for an active adult (estimated between 9360 kJ [3327 kcal] and 14,580 kJ [3485 kcal] per day). Because they are easy to process, this would have made tortoises a highly-ranked resource, but their slow growth and reproduction makes them susceptible to over-exploitation. Zooarchaeological abundance data show that during the ca. 75 ka (thousands of years) upper Still Bay M1 phase at BBC, tortoises contributed twice as many calories to the diet relative to ungulates than they did during the ca. 100 ka lower M3 phase. However, in spite of the abundance of their fossils, their absolute caloric contribution relative to ungulates remained modest in both phases. At the end of the site's MSA occupation history, human subsistence strategies shifted to emphasise high-return large hunted mammals, which likely precipitated changes in the social roles of hunters and gatherers during the Still Bay. | [
"The Study of the Human Past",
"Environmental Biology, Ecology and Evolution"
]
|
680156 | The Pancreas Regulome: From causality to prediction of non-coding mutations in human pancreatic diseases | Several human pancreatic diseases have been characterized, being the diabetes the most common. Like others, this genetic disease is related to disrupted non-coding cis-regulatory elements (CREs) that culminate in altered gene expression. Although Genome Wide Association Studies support this hypothesis, it’s still unclear how mutations on CREs contribute to disease. The translation from the “non-coding code” to phenotype is an exciting and unexplored field that we will approach in this project with the help of the zebrafish as a suitable animal model. We aim to uncover the implications of the disruption of pancreas CREs and how they contribute to diabetes in vivo. For this we will study transcriptional regulation of genes in zebrafish. The similarities between zebrafish and mammal pancreas and the evolutionary conservation of pancreas transcription factors (TF) make it an excellent model to approach and study this disease. In this project we will characterize the zebrafish insulin producing beta-cell regulome, by determining the active CREs in this cell type and their bound TFs. Then we will compare this information with a similar dataset recently available for human beta-cells, to define functional orthologs in these species. Selected CREs will be tested by in vivo gene reporter assays in zebrafish, focusing on those functionally equivalent to human CREs where risk alleles have been associated with diabetes or those regulating genes involved in diabetes. Later these CREs will be mutated in the zebrafish genome to validate their contribution to diabetes. Finally we will translate this to predict new human disease-associated CREs by focusing on the regulatory landscape of diabetes-associated genes, without the need of having countless patients to uncover them. With this project we will create a model system that will allow the identification of new diabetes-associated CREs, which might have a great impact in clinical management of this epidemic disease. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
W744683817 | Spatially resolved X-ray micro/nano-spectroscopy and imaging on the model organism Daphnia magna using laboratory and synchrotron sources | This work demonstrates and further develops spatially resolved laboratory and synchrotron X-ray spectroscopic and imaging experiments to answer specific ecotoxicological questions on the model organism Daphnia magna. The first phase of this work consisted of developing appropriate sample preparation procedures for this organism in order to be able to perform X-ray analyses on Daphnia magna subjected to ecotoxicological experiments. In the second phase, X-ray set-ups at different laboratories and synchrotron facilities were optimized and characterized in order to be able to perform the X-ray spectral imaging experiments of interest on Daphnia magna. Finally, various data reduction strategies were employed to process the vast amount of spectral data for evaluation and interpretation. | [
"Physical and Analytical Chemical Sciences",
"Environmental Biology, Ecology and Evolution"
]
|
284340 | Sailing into Modernity: Comparative Perspectives on the Sixteenth and Seventeenth Century European Economic Transition | This research project analyses the economic transition in Early Modern Europe through an innovative and interdisciplinary approach that will employ tools from legal, economic and social history for the comparative analysis of the legal position and the economic treatment of sailors active in the Mediterranean. Since Fernand Braudel coined the expression ‘invasion of the northerners’, the subject of how English and Dutch shipping overtook local Mediterranean powers has been a classic topic of economic history. But due to the poor survival of traditional economic documentation for this period, we still know little about the details of how this happened in practice, and existing debates are stalling because of a lack of detailed comparative research. This project offers the opportunity to move these debates forward by analysing alternative documentary evidence (from judicial and notarial archives), which allows considerable methodological advances through the detailed comparative analysis of the protagonists’ trading strategies. It is a central contention of this project that legal and financial differences in the treatment of crews were one of the crucial factors in the success of northern European economies in their commercial penetration of the Mediterranean, a necessary step in their struggle for global hegemony. A comparative approach to the study of wage controversies in four European economies which had a strong maritime sector – Italy, England, France, Netherlands – will bring new light on the everyday legal cases with which international commercial law was being formulated on the ground, and with an interesting new perspective of the effect of economic activities on the development of legal institutions. These topics have also a strong connection to contemporary issues such as how a mature economy (the early modern Italian) reacted to a structural crisis and the aggressive competition of rising economic and political powers (England, United Provinces). | [
"The Study of the Human Past",
"Individuals, Markets and Organisations"
]
|
864483 | Novel Oxides and Topological Interfaces for quantum Computing Electronics | Today’s quantum computers are suffering from a very high error rate due to decoherence (i.e. loss of quantum information) in their qubits fabricated with superconductors junctions or semiconductors quantum dots. The goal of this proposal is to research radically new materials and architectures to build a “fault-tolerant” qubit device on Silicon substrate (i.e. scalable), that will be immune to decoherence problems.
In NOTICE, we will design and synthetize novel crystalline perovskite materials, monolithically integrated on a Silicon substrate, with topological insulating properties to enable the generation of Majorana fermions at the heterointerface with a superconductor. The generated Majorana fermions will hold the quantum information in such “Majorana qubit” which will be resistant to noises and fluctuations due to the topology effect if stable and robust materials presenting the desired properties can be obtained.
Bismuth-based perovskites were down-selected as topological insulator (BaBi(O,F)3) and superconductor ((Ba,K)BiO3) oxides due to the very strong Spin Orbit Coupling present in Bi which will favorize the efficient generation of Majorana fermions at the perfect (pristine) BaBi(O,F)3/(Ba,K)BiO3 heterointerface. With Molecular Beam Epitaxy growth approach together with advanced characterization techniques such as Angle-Resolved PhotoEmission Spectroscopy measurements and ab-initio simulations on the topological insulating properties of the perovskites, we aim to generate a stable topological interface leading to the efficient generation of Majorana fermions. This breakthrough will enable us to fabricate chiral Majorana devices on a Silicon technology platform, providing both reliability and manufacturing scalability.
NOTICE results will pave the way to “fault-tolerant” qubit, bringing a paradigm shift in quantum computing by reducing drastically the gap between logical and physical qubits and the need for quantum error correction algorithms. | [
"Condensed Matter Physics",
"Synthetic Chemistry and Materials",
"Computer Science and Informatics",
"Materials Engineering"
]
|
W2338352461 | Electricity in Europe: exiting fossil fuels? | There are many options for generating electricity with low carbon emissions, and the elec- trification of heat and transport can decarbonize energy use across the economy. This places the power sector at the forefront of any move away from fossil fuels, even though fossil-fuelled generators are more dependable and flexible than nuclear reactors or intermittent renewables, and vital for the second- by-second balancing of supply and demand. Renewables tend to supplement, rather than replace, fos- sil capacity, although output from fossil-fuelled stations will fall and some will have to retire to avoid depressing wholesale power prices. At times of low demand and high renewable output prices can turn negative, but electricity storage, long-distance interconnection, and flexible demand may develop to absorb any excess generation. Simulations for Great Britain show that while coal may be eliminated from the mix within a decade, natural gas has a long-term role in stations with or without carbon cap- ture and storage, depending on its cost and the price of carbon. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
10.1007/978-3-030-31784-3_22 | Efficient Trace Encodings Of Bounded Synthesis For Asynchronous Distributed Systems | The manual implementation of distributed systems is an error-prone task because of the asynchronous interplay of components and the environment. Bounded synthesis automatically generates an implementation for the specification of the distributed system if one exists. So far, bounded synthesis for distributed systems does not utilize their asynchronous nature. Instead, concurrent behavior of components is encoded by all interleavings and only then checked against the specification. We close this gap by identifying true concurrency in synthesis of asynchronous distributed systems represented as Petri games. This defines when several interleavings can be subsumed by one true concurrent trace. Thereby, fewer and shorter verification problems have to be solved in each iteration of the bounded synthesis algorithm. For Petri games, experimental results show that our implementation using true concurrency outperforms the implementation based on checking all interleavings. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
W2036483312 | Ultrasonically improved galvanochemical technology for the remediation of industrial wastewater | Two general methodologies adopted for the decontamination of industrial wastewater containing oil and metal ions are flocculation and coagulation. Both methods require the addition of chemicals and in the case of electrocoagulation the additional use of electrical power. Another methodology that was developed in Russia some years ago involves the production of Fe2O3 particles as coagulants by a galvanochemical reaction between iron and coke. Both of these materials are inexpensive and generally available in bulk. Ultrasonic processing of the particles generated in this reaction reduces the particle size of the Fe2O3 particles and provides surface cleaning making them more effective. Trials have proved their efficiency for the decontamination of wastewater made up in a laboratory and real wastewater from a carriage cleaning station on the St. Petersburg Metro. A mathematical model for the process has been developed. | [
"Products and Processes Engineering",
"Environmental Biology, Ecology and Evolution"
]
|
10.3390/biology6010005 | A molecular view of kinetochore assembly and function | Kinetochores are large protein assemblies that connect chromosomes to microtubules of the mitotic and meiotic spindles in order to distribute the replicated genome from a mother cell to its daughters. Kinetochores also control feedback mechanisms responsible for the correction of incorrect microtubule attachments, and for the coordination of chromosome attachment with cell cycle progression. Finally, kinetochores contribute to their own preservation, across generations, at the specific chromosomal loci devoted to host them, the centromeres. They achieve this in most species by exploiting an epigenetic, DNA-sequence-independent mechanism; notable exceptions are budding yeasts where a specific sequence is associated with centromere function. In the last 15 years, extensive progress in the elucidation of the composition of the kinetochore and the identification of various physical and functional modules within its substructure has led to a much deeper molecular understanding of kinetochore organization and the origins of its functional output. Here, we provide a broad summary of this progress, focusing primarily on kinetochores of humans and budding yeast, while highlighting work from other models, and present important unresolved questions for future studies. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W2603535217 | Følner functions and the generic Word Problem for finitely generated amenable groups | We introduce and investigate different definitions of effective amenability, in terms of computability of F{\o}lner sets, Reiter functions, and F{\o}lner functions. As a consequence, we prove that recursively presented amenable groups have subrecursive F{\o}lner function, answering a question of Gromov, for the same class of groups we prove that solvability of the Equality Problem on a generic set (generic EP) is equivalent to solvability of the Word Problem on the whole group (WP), thus providing the first examples of finitely presented groups with unsolvable generic EP. In particular, we prove that for finitely presented groups, solvability of generic WP doesn't imply solvability of generic EP. | [
"Mathematics",
"Computer Science and Informatics"
]
|
W1588650177 | Spatial Downscaling of TRMM Precipitation Product Using a Combined Multifractal and Regression Approach: Demonstration for South China | Abstract: The lack of high spatial resolution precipitation data, which are crucial for the modeling and managing of hydrological systems, has triggered many attempts at spatial downscaling. The essence of downscaling lies in extracting extra information from a dataset through some scale-invariant characteristics related to the process of interest. While most studies utilize only one source of information, here we propose an approach that integrates two independent information sources, which are characterized by self-similar and relationship with other geo-referenced factors, respectively. This approach is applied to 16 years (1998–2013) of TRMM 3B43 monthly precipitation data in an orographic and monsoon influenced region in South China. Elevation, latitude, and longitude are used as predictive variables in the regression model, while self-similarity is characterized by multifractals and modeled by a log-normal multiplicative random cascade. The original 0.25° precipitation field was downscaled to the 0.01° scale. The result was validated with rain gauge data. Good consistency was achieved on coefficient of determination, bias, and root mean square error. This study contributes to the current precipitation downscaling | [
"Mathematics",
"Earth System Science"
]
|
10.1007/s13171-018-0124-z | Moderate Deviations for Ewens-Pitman Sampling Models | Consider a population of individuals belonging to an infinity number of types, and assume that type proportions follow the Poisson-Dirichlet distribution with parameter α ∈ [0,1) and 𝜃 > −α. Given a sample of size n from the population, two important statistics are the number Kn of different types in the sample, and the number Ml,n of different types with frequency l in the sample. We establish moderate deviation principles for (Kn)n≥ 1 and (Ml,n)n≥ 1. Corresponding rate functions are explicitly identified, which help in revealing a critical scale and in understanding the exact role of the parameters α and 𝜃. | [
"Mathematics"
]
|
10.1039/c8ee00875b | Topological and network analysis of lithium ion battery components: the importance of pore space connectivity for cell operation | Pore space connectivity is a useful metric for describing microstructure of lithium ion battery components. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1093/hmg/ddy425 | A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease | The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives, and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization. Our pipeline detects somatic variants with allele fractions as low as 0. 5% and achieves a replication rate of >55%. Validation in an independent data set demonstrates excellent performance (sensitivity > 57%, specificity > 98%, replication rate > 80%). We applied this pipeline to the autoimmune disease multiple sclerosis (MS) as a proof-of-principle. We demonstrate that 60% of MS patients carry 2-10 exonic somatic variants in their peripheral blood T and B cells, with the vast majority (80%) occurring in T cells and variants persisting over time. Synonymous variants significantly co-occur with non-synonymous variants. Systematic characterization indicates somatic variants are enriched for being novel or very rare in public databases of germline variants and trend towards being more damaging and conserved, as reflected by higher phred-scaled combined annotation-dependent depletion (CADD) and genomic evolutionary rate profiling (GERP) scores. Our pipeline and proof-of-principle now warrant further investigation of common somatic genetic variation on top of inherited genetic variation in the context of autoimmune disease, where it may offer subtle survival advantages to immune cells and contribute to the capacity of these cells to participate in the autoimmune reaction. | [
"Immunity, Infection and Immunotherapy",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
]
|
10.1037/a0013738 | Additive and Interactive Effects of Stimulus Degradation: No Challenge for CDP+ | S. O'Malley and D. Besner (2008) showed that additive effects of stimulus degradation and word frequency in reading aloud occur in the presence of nonwords but not in pure word lists. They argued that this dissociation presents a major challenge to interactive computational models of reading aloud and claimed that no currently implemented model is able to simulate additive effects in these conditions. In the current article, it is shown that the connectionist dual process model (CDP+) can simulate these effects because its nonlexical route is thresholded. The authors present a series of simulations showing that CDP+ can not only simulate the precise dissociation observed by O'Malley and Besner but more generally can produce additive effects for a wide range of parameter combinations and different sets of items. The nonlexical route of CDP+ was not modified post hoc to deal with the effects of stimulus quality, but it had been thresholded for principled reasons before it was known that these effects existed. Together, the effects of stimulus quality on word frequency do not challenge CDP+ but rather provide unexpected support for its architecture and processing dynamics. | [
"The Human Mind and Its Complexity",
"Computer Science and Informatics"
]
|
DE 102007010531 A | Integriertes Digitalradio-Modul | Die Erfindung betrifft ein Audio-Unterhaltungssystem, welches eine Primärschaltkreis-Platine mit einem Prozessor aufweist, der mit einem Antenneneingang, einem Audio-Ausgang und einem Verbinder-Bauteil in Verbindung steht. Der Prozessor ist so konfiguriert, dass er gegebenenfalls das Vorhandensein einer digitalen Audioschaltkreis-Platine erkennt und ein Audiosignal, welches auf einem Funksignal beruht, an den Audioausgang ausgibt. Das Funksignal kann ein amplitudenmoduliertes Signal, ein frequenzmoduliertes (Ultrakurzwellen) Signal oder ein digitales satellitenbasiertes Signal sein. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
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