pinecone/core-2020-05-10-deduplication huggingface dataset:
Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours of glycogen storage disease type 1a in mice

International audienceGlycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency in theglucose-6-phosphatase catalytic subunit (encoded by G6pc), which is essential forendogenous glucose production. Despite strict diet control to maintain blood glucose, patientswith GSD1a develop hepatomegaly, steatosis and then hepatocellular adenomas (HCA),which can undergo malignant transformation. Recently, gene therapy has attracted attention asa potential treatment for GSD1a. In order to maintain long-term transgene expression, wedeveloped an HIV-based vector, which allowed us to specifically express the human G6PCcDNA in the liver. We analysed the efficiency of this lentiviral vector in the prevention of thedevelopment of the hepatic disease in an original GSD1a mouse model, which exhibitsG6Pase deficiency exclusively in the liver (L-G6pc-/- mice). Recombinant lentivirus wereinjected in B6.G6pcex3lox/ex3lox.SAcreERT2/w neonates and G6pc deletion was induced bytamoxifen treatment at weaning. Magnetic resonance imaging was then performed to followup the development of hepatic tumours. Lentiviral gene therapy restored glucose-6phosphatase activity sufficient to correct fasting hypoglycaemia during 9 months. Moreover,lentivirus-treated L-G6pc-/- mice presented normal hepatic triglyceride levels, whereasuntreated mice developed steatosis. Glycogen stores were also decreased although liverweight remained high. Interestingly, lentivirus-treated L-G6pc-/- mice were protected againstthe development of hepatic tumours after 9 months of gene therapy while most of untreated LG6pc-/-mice developed millimetric HCA. Thus the treatment of new-borns by recombinantlentivirus appears as an attractive approach to protect the liver from the development ofsteatosis and hepatic tumours associated to GSD1a pathology
Low-cost photomask fabrication using laser ablation

International audienceA specific fabrication process has been developed to produce low-cost photomasks using standard consumer products. This process is based on an indirect route, using a numerically-controlled excimer laser (KrF) etching technique. It begins with RF-sputtering deposition of a titanium film (200 nm-thick) on float glass substrate. Then a nitrocellulose lacquer, serving as a self-developing resist, is spin-coated on titanium. It is ablated with partially-overlapping laser impacts and undergoes self-combustion under laser beam. Proper heat treatments are applied before and after laser ablation to circumvent smearing and adhesion problems. Finally the titanium layer is wet etched through the openings in the resist by dilute hydrofluoric acid. Both nitrocellulose lacquer characterization and laser parameters are discussed. The resolution achieved here (10 μm, limited by diffraction effects of the laser optics and by side heating of the resist due to the titanium film) is suitable for the fabrication of microwave devices. To confirm the suitability of the proposed process, several photomasks have been fabricated to pattern coplanar tunable stub resonators on ferroelectric KTa0.5Nb0.5O3 thin films. The dielectric permittivity of the KTa0.5Nb0.5O3 material is controlled by DC biasing. A 18% tunability of the stub resonance frequency has been measured in X-band (close to 10 GHz), validating thereby the whole patterning process
Composing JSON-based Web APIs

International audienceThe development of Web APIs has become a discipline that companies have to master to succeed in the Web. The so-called API economy is pushing companies to provide access to their data by means of Web APIs, thus requiring web developers to study and integrate such APIs into their applications. The exchange of data with these APIs is usually performed by using JSON, a schemaless data format easy for computers to parse and use. While JSON data is easy to read, its structure is implicit, thus entailing serious problems when integrating APIs coming from di erent vendors. Web developers have therefore to understand the domain behind each API and study how they can be composed. We tackle this issue by presenting an approach able to both discover the domain of JSON-based Web APIs, and identify composition links among them. Our approach allows developers to easily visualize what is behind APIs and how they can be composed to be used in their applications
Which market protocols facilitate fair trading?

The evaluation of an exchange market is a multi-faceted problem. An important criterion is the ability to achieve allocative efficiency. Gode and Sunder (1993) shows that a continuous double auction for singleunit trades leads to an efficient allocation even when the traders exhibit “zero-intelligence”; in other words, market protocols are active contributors in the search for a better outcome. Under reasonable circumstances, most of the commonly used market protocols share the ability to help traders discover an efficient allocation
On the functions counting walks with small steps in the quarter plane

40 pages, 17 figuresInternational audienceModels of spatially homogeneous walks in the quarter plane ${\bf Z}_+^{2}$ with steps taken from a subset $\mathcal{S}$ of the set of jumps to the eight nearest neighbors are considered. The generating function $(x,y,z)\mapsto Q(x,y;z)$ of the numbers $q(i,j;n)$ of such walks starting at the origin and ending at $(i,j) \in {\bf Z}_+^{2}$ after $n$ steps is studied. For all non-singular models of walks, the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are continued as multi-valued functions on ${\bf C}$ having infinitely many meromorphic branches, of which the set of poles is identified. The nature of these functions is derived from this result: namely, for all the $51$ walks which admit a certain infinite group of birational transformations of ${\bf C}^2$, the interval $]0,1/|\mathcal{S}|[$ of variation of $z$ splits into two dense subsets such that the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are shown to be holonomic for any $z$ from the one of them and non-holonomic for any $z$ from the other. This entails the non-holonomy of $(x,y,z)\mapsto Q(x,y;z)$, and therefore proves a conjecture of Bousquet-Mélou and Mishna
Short-wavelength stability analysis of thin vortex rings

The linear stability of thin vortex rings are studied by short-wavelength stability analysis. The modified Hill–Schrödinger equation for vortex rings, which incorporates curvature effect, is derived. It is used to evaluate growth rates analytically. The growth rates are also evaluated by numerical calculation and they agree well with analytical values for small  which is the ratio of core radius to ring radius. Two types of vortex rings are considered: Kelvin's vortex ring and a Gaussian vortex ring. For Kelvin's vortex ring the maximum first-order growth rate is found to be 1.65/2.56. For the Gaussian vortex ring the first-order growth rate is larg
2,000 families: identifying the research potential of an origins-of-migration study

Despite recent advances, critical areas in the analysis of European migration remain underdeveloped. We have only a limited understanding of the consequences of migration for migrants and their descendants, relative to staying behind; and our insights of intergenerational transmission is limited to two generations of those living in the destination countries. These limitations stem from a paucity of studies that incorporate comparison with non-migrants – and return migrants – in countries of origin and which trace processes of intergenerational transmission over multiple generations. This paper outlines the theoretical and methodological discussions in the field, design and data of the 2,000 Families study. The study comprises almost 50,000 members of migrant and non-migrant Turkish families across three family generations, living in Turkey and eight European countries. We provide indicative findings from the study, framed within a theoretical perspective of “dissimilation” from origins, and reflect on its potential for future migration research
Embryonic cerebrospinal fluid regulates neuroepithelial survival proliferation and neurogenesis in chick embryos

Producción CientíficaEarly in development, the  behavior of neuroepithelial cells is controlled by several factors, which  act  in  a developmentally regulated manner. Dif- fusible factors are  secreted locally  by the  neuroepithelium itself, although other nearby structures may  also  be involved. Evidence suggests a physio- logical role for the  cerebrospinal ﬂuid  in the  development of the  brain. Here, using organotypic cultures of chick  embryo neuroepithelial explants from the  mesencephalon, we show that the  neuroepithelium in vitro  is not able to self-induce cell survival, replication, and  neurogenesis. We also  show  that the  embryonic cerebrospinal ﬂuid  (E-CSF) promotes neuroepithelial stem cell survival and  induces proliferation and  neurogenesis in  mesencephalic explants. These data strongly suggest that E-CSF is involved in the  regu- lation of neuroepithelial cells behavior, supporting the  hypothesis that this ﬂuid  plays a key  role  during the  early development of the  central nervous system
Exact and efficient top-K inference for multi-target prediction by querying separable linear relational models

Many complex multi-target prediction problems that concern large target spaces are characterised by a need for efficient prediction strategies that avoid the computation of predictions for all targets explicitly. Examples of such problems emerge in several subfields of machine learning, such as collaborative filtering, multi-label classification, dyadic prediction and biological network inference. In this article we analyse efficient and exact algorithms for computing the top-K predictions in the above problem settings, using a general class of models that we refer to as separable linear relational models. We show how to use those inference algorithms, which are modifications of well-known information retrieval methods, in a variety of machine learning settings. Furthermore, we study the possibility of scoring items incompletely, while still retaining an exact top-K retrieval. Experimental results in several application domains reveal that the so-called threshold algorithm is very scalable, performing often many orders of magnitude more efficiently than the naive approach
Discovery of a quinoline-4-carboxamide derivative with a novel mechanism of action, multistage antimalarial activity, and potent in vivo efficacy

The antiplasmodial activity, DMPK properties, and efficacy of a series of quinoline-4-carboxamides are described. This series was identified from a phenotypic screen against the blood stage of Plasmodium falciparum (3D7) and displayed moderate potency but with suboptimal physicochemical properties and poor microsomal stability. The screening hit (1, EC50 = 120 nM) was optimized to lead molecules with low nanomolar in vitro potency. Improvement of the pharmacokinetic profile led to several compounds showing excellent oral efficacy in the P. berghei malaria mouse model with ED90 values below 1 mg/kg when dosed orally for 4 days. The favorable potency, selectivity, DMPK properties, and efficacy coupled with a novel mechanism of action, inhibition of translation elongation factor 2 (PfEF2), led to progression of 2 (DDD107498) to preclinical development
Angiotensin type 1A receptor regulates β-arrestin binding of the β2-adrenergic receptor via heterodimerization

Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane. While candesartan, a conventional AT1R antagonist, had no effect on the β-arrestin2 binding to β2AR, TRV120023, a β-arrestin biased agonist, enhanced the interaction. These findings reveal a new crosstalk mechanism between AT1R and β2AR, and suggest that enhanced β-arrestin2 binding to β2AR can contribute to the pharmacological effects of biased AT1R agonists. © 201
Global shifts in genome and proteome composition are very tightly coupled

The amino acid composition (AAC) of proteomes differs greatly between microorganisms and is associated with the environmental niche they inhabit, suggesting that these changes may be adaptive. Similarly, the oligonucleotide composition of genomes varies and may confer advantages at the DNA/RNA level. These influences overlap in protein-coding sequences, making it difficult to gauge their relative contributions. We disentangle these effects by systematically evaluating the correspondence between intergenic nucleotide composition, where protein-level selection is absent, the AAC, and ecological parameters of 909 prokaryotes. We find that G + C content, the most frequently used measure of genomic composition, cannot capture diversity in AAC and across ecological contexts. However, di-/trinucleotide composition in intergenic DNA predicts amino acid frequencies of proteomes to the point where very little cross-species variability remains unexplained (91% of variance accounted for). Qualitatively similar results were obtained for 49 fungal genomes, where 80% of the variability in AAC could be explained by the composition of introns and intergenic regions. Upon factoring out oligonucleotide composition and phylogenetic inertia, the residual AAC is poorly predictive of the microbes’ ecological preferences, in stark contrast with the original AAC. Moreover, highly expressed genes do not exhibit more prominent environment-related AAC signatures than lowly expressed genes, despite contributing more to the effective proteome. Thus, evolutionary shifts in overall AAC appear to occur almost exclusively through factors shaping the global oligonucleotide content of the genome. We discuss these results in light of contravening evidence from biophysical data and further reading frame-specific analyses that suggest that adaptation takes place at the protein level
Horseradish and soybean peroxidases: comparable tools for alternative niches?

Horseradish and soybean peroxidases (HRP and SBP, respectively) are useful biotechnological tools. HRP is often termed the classical plant heme peroxidase and although it has been studied for decades, our understanding has deepened since its cloning and subsequent expression, enabling numerous mutational and protein engineering studies. SBP, however, has been neglected until recently, despite offering a real alternative to HRP: SBP actually outperforms HRP in terms of stability and is now used in numerous biotechnological applications, including biosensors. Review of both is timely. This article summarizes and discusses the main insights into the structure and mechanism of HRP, with special emphasis on HRP mutagenesis, and outlines its use in a variety of applications. It also reviews the current knowledge and applications to date of SBP, particularly biosensors. The final paragraphs speculate on the future of plant heme-based peroxidases, with probable trends outlined and explored
Selecting features for object detection using an AdaBoost-compatible evaluation function

This paper addresses the problem of selecting features in a visual object detection setup where a detection algorithm is applied to an input image represented by a set of features. The set of features to be employed in the test stage is prepared in two training-stage steps. In the first step, a feature extraction algorithm produces a (possibly large) initial set of features. In the second step, on which this paper focuses, the initial set is reduced using a selection procedure. The proposed selection procedure is based on a novel evaluation function that measures the utility of individual features for a certain detection task. Owing to its design, the evaluation function can be seamlessly embedded into an AdaBoost selection framework. The developed selection procedure is integrated with state-of-the-art feature extraction and object detection methods. The presented system was tested on five challenging detection setups. In three of them, a fairly high detection accuracy was effected by as few as six features selected out of several hundred initial candidates.\u
Synthesis of monoclinic Celsian from coal fly ash by using a one-step solid-state reaction

Monoclinic (Celsian) and hexagonal (Hexacelsian) Ba1−xSrxAl2Si2O8 solid solutions, where x = 0, 0.25, 0.375, 0.5, 0.75 or 1, were synthesized by using Coal Fly Ash (CFA) as main raw material, employing a simple one-step solid-state reaction process involving thermal treatment for 5 h at 850–1300 °C. Fully monoclinic Celsian was obtained at 1200 °C/5 h, for SrO contents of 0.25 ≤ x ≤ 0.75. However, an optimum SrO level of 0.25 ≤ x ≤ 0.375 was recommended for the stabilization of Celsian. These synthesis conditions represent a significant improvement over the higher temperatures, longer times and/or multi-step processes needed to obtain fully monoclinic Celsian, when other raw materials are used for this purpose, according to previous literature. These results were attributed to the role of the chemical and phase constitution of CFA as well as to a likely mineralizing effect of CaO and TiO2 present in it, which enhanced the Hexacelsian to Celsian conversion
Spin magnetotransport in a two-dimensional electron system\ud
confined in a quantum well

We show a simple model that computes the magnetoconduction in a two-dimensional electron system (2DES) where the spin is another degree of freedom in the system. The 2DES is confined in a quantum well (QW) immersed in a heterostructure, where the Rashba spin–orbit interaction is present. When an external magnetic field is applied to the system, the competition between the spin–orbit interaction and the Zeeman effect on the magnetoconduction of the 2DES is analysed, in the cases where one or two sub-bands are occupied in the QW. In the model different spin-oriented 2DES can be treated independently, with a spin current associated with each system. The model has been tested with experimental results obtained from a 2DES formed in an InGaAs layer
An approach to automatic learning assessment based on the computational theory of perceptions

E-learning systems output a huge quantity of data on a learning process. However, it takes a lot of specialist\ud
human resources to manually process these data and generate an assessment report. Additionally, for formative assessment, the report should state the attainment level of the learning goals defined by the instructor. This paper describes the use of the granular linguistic model of a phenomenon (GLMP) to model the assessment of the learning process and implement the automated generation of an assessment report. GLMP is based on fuzzy logic and the computational theory of perceptions. This technique is useful for implementing complex assessment criteria using inference systems based on linguistic rules. Apart from\ud
the grade, the model also generates a detailed natural language progress report on the achieved proficiency level, based exclusively on the objective data gathered from correct and incorrect responses. This is illustrated by applying the model to the assessment of Dijkstra’s algorithm learning using a visual simulation-based graph algorithm learning environment, called GRAPH
Text categorization methods for automatic estimation of verbal intelligence

In this paper we investigate whether conventional text categorization methods may suffice to infer different verbal intelligence levels. This research goal relies on the hypothesis that the vocabulary that speakers make use of reflects their verbal intelligence levels. Automatic verbal intelligence estimation of users in a spoken language dialog system may be useful when defining an optimal dialog strategy by improving its adaptation capabilities. The work is based on a corpus containing descriptions (i.e. monologs) of a short film by test persons yielding different educational backgrounds and the verbal intelligence scores of the speakers. First, a one-way analysis of variance was performed to compare the monologs with the film transcription and to demonstrate that there are differences in the vocabulary used by the test persons yielding different verbal intelligence levels. Then, for the classification task, the monologs were represented as feature vectors using the classical TF–IDF weighting scheme. The Naive Bayes, k-nearest neighbors and Rocchio classifiers were tested. In this paper we describe and compare these classification approaches, define the optimal classification parameters and discuss the classification results obtained
On the Uncertainty of CFD in Sail Aerodynamics

A verification and validation procedure for yacht sail aerodynamics is presented. Guidelines and an example of application are provided. The grid uncertainty for the aerodynamic lift, drag and pressure distributions for the sails is computed. The pressures are validated against experimental measurements, showing that the validation procedure may allow the identification of modelling errors. Lift, drag and L2 norm of the pressures were computed with uncertainties of the order of 1%. Convergence uncertainty and round-off uncertainty are several orders of magnitude smaller than the grid uncertainty. The uncertainty due to the dimension of the computational domain is computed for a flat plate at incidence and is found to be significant compared with the other uncertainties. Finally, it is shown how the probability that the ranking between different geometries is correct can be estimated knowing the uncertainty in the computation of the value used to rank
Implementation of the Hardy-Cross method for the solution of piping networks

This paper describes a user-friendly software for the calculation of general piping system networks composed of virtually any parallel and series pipe arrangement. Solution of the network is made with recourse to the iterative method of Hardy Cross. Solution is provided for pressure and flow-rate in each branch. Dimensioning problems, where pump characteristics or a pipe diameter are sought for achieving a pre-specified flow-rate condition, may also be tackled. © 2004 Wiley-Liss, Inc. © 2004 Wiley Periodicals, Inc. Comput Appl Eng Educ 12: 117-125, 2004; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20006http://dx.doi.org/10.1002/cae.2000
Cellulose Derivatives Membranes as Supports for Immobilisation of Enzymes

Cellulosic derivatives (cellulose acetate, cellulose propionate and cellulose acetate-butyrate) as membranes, were prepared in different ways. These were then characterised by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and contact angle evaluation. Subsequently, catalase (H2O2:H2O2 oxireductase; EC 1.11.1.6), alcohol oxidase (Alcohol:oxygen oxireductase; EC 1.1.3.13) and glucose oxidase (ß-D- Glucose:oxygen 1-oxireductase; EC 1.1.3.4) were covalently linked to these membranes. The catalytic activity and stability of these enzymes, when immobilised, were examined. The results obtained showed that the immobilisation efficiency and the stability of the coupled enzymes could be correlated with the studied properties of the supports. The cellulose acetate membrane which was prepared by evaporation gave the more active conjugate support-enzyme. Membranes prepared by the immersion technique were more crystalline and therefore less suitable for enzyme immobilisation. The highly hydrophobic membranes, obtained from the propionate and the butyrate esters of cellulose reduced the activities but gave better storage stability.http://dx.doi.org/10.1023/A:100925512627