High sensitivity phonon-mediated kinetic inductance detector with combined amplitude and phase read-out

The development of wide-area cryogenic light detectors with good energy resolution is one of the priorities of next generation bolometric experiments searching for rare interactions, as the simultaneous read-out of the light and heat signals enables background suppression through particle identification. Among the proposed technological approaches for the phonon sensor, the naturally-multiplexed Kinetic Inductance Detectors (KIDs) stand out for their excellent intrinsic energy resolution and reproducibility. To satisfy the large surface requirement (several cm$^2$) KIDs are deposited on an insulating substrate that converts the impinging photons into phonons. A fraction of phonons is absorbed by the KID, producing a signal proportional to the energy of the original photons. The potential of this technique was proved by the CALDER project, that reached a baseline resolution of 154$\pm$7 eV RMS by sampling a 2$\times$2 cm$^2$ Silicon substrate with 4 Aluminum KIDs. In this paper we present a prototype of Aluminum KID with improved geometry and quality factor. The design improvement, as well as the combined analysis of amplitude and phase signals, allowed to reach a baseline resolution of 82$\pm$4 eV by sampling the same substrate with a single Aluminum KID

Development of Lumped Element Kinetic Inductance Detectors for the W-Band

We are developing a Lumped Element Kinetic Inductance Detector (LEKID) array able to operate in the W-band (75-110 GHz) in order to perform ground-based Cosmic Microwave Background (CMB) and mm-wave astronomical observations. The W-band is close to optimal in terms of contamination of the CMB from Galactic synchrotron, free-free, and thermal interstellar dust. In this band, the atmosphere has very good transparency, allowing interesting ground-based observations with large (>30 m) telescopes, achieving high angular resolution (<0.4 arcmin). In this work we describe the startup measurements devoted to the optimization of a W-band camera/spectrometer prototype for large aperture telescopes like the 64 m SRT (Sardinia Radio Telescope). In the process of selecting the best superconducting film for the LEKID, we characterized a 40 nm thick Aluminum 2-pixel array. We measured the minimum frequency able to break CPs (i.e. $h\nu=2\Delta\left(T_{c}\right)=3.5k_{B}T_{c}$) obtaining $\nu=95.5$ GHz, that corresponds to a critical temperature of 1.31 K. This is not suitable to cover the entire W-band. For an 80 nm layer the minimum frequency decreases to 93.2 GHz, which corresponds to a critical temperature of 1.28 K; this value is still suboptimal for W-band operation. Further increase of the Al film thickness results in bad performance of the detector. We have thus considered a Titanium-Aluminum bi-layer (10 nm thick Ti + 25 nm thick Al, already tested in other laboratories), for which we measured a critical temperature of 820 mK and a cut-on frequency of 65 GHz: so this solution allows operation in the entire W-band.Comment: 16th International Workshop on Low Temperature Detectors, Grenoble 20-24 July 2015, Journal of Low Temperature Physics, Accepte

Modelos de entonación analítico y fonético-fonológico aplicados a una base de datos del español de Buenos Aires

En este trabajo evaluamos un modelo analítico-cuantitativo y otro fonéticofonológico de las características entonativas obtenidas para una base de datos de 741 oraciones declarativas de foco amplio para el español de Buenos Aires. La descripción cuantitativa es la resultante de la aplicación del modelo de superposición de contornos de frecuencia fundamental propuesto por Fujisaki (2003) para diversas lenguas. La descripción fonética que utiliza la marcación de índices de juntura y tono ToBI (Beckman y Ayers, 1993) surge de la percepción de los grupos entonativos y de las prominencias y la aplicación de un método de etiquetado manual (Gurlekian y otros, 2001b), denominado ToBI ampliado (ToBIA). Los resultados obtenidos, extienden la validez del modelo analítico para un gran número de oraciones declarativas de foco amplio del español. Asimismo se comprueba la validez del ToBI-A para producir un contorno de entonación comparable con el real a partir de las nuevas etiquetas propuestas. Para este fin, se realiza una prueba perceptual de comparación por pares y se calculan los errores respecto de la curva real que resultan ser del mismo orden para ambos modelos. También se verifica la validez del ToBI-A en las aplicaciones de síntesis de habla y para la definición fonológica de los acentos tonales de variedades no estudiadas del español.We evaluate here the application of two intonational models –quantitative and phonetic- to the analysis of an Argentine Spanish database of 741 broad-focus declarative sentences. The analytic model is the superpositional model proposed by Fujisaki (2003) for several languages. The phonetic model is the result of the application of a labelling method (Gurlekian et al., 2001b) that incorporates psycho-acoustic measurements and a detailed description of the shape of the accent. Parameters generated by this labelling method were used to synthesize the intonational contours, which were then evaluated in a perception test. Results indicate the validity of Fujisaki´s model for describing a large database of Spanish broad-focus declaratives, and, thus, suggest the importance of Fujisaki’s model for speech technology applications. The extended ToBI model (ToBI-A) is validated by the correlation coefficient and RMSE values as well as the results of the perception test. Ten native speakers of the variety under study judged the synthesized sentences as highly natural with only minor differences with the original contour. These results indicate that the ToBI-A (i) is adequate for a linguistically-meaningful description of the intonation of a new variety; (ii) can be adequately used for modelling intonation.En este trabajo evaluamos un modelo analítico-cuantitativo y otro fonéticofonológico de las características entonativas obtenidas para una base de datos de 741 oraciones declarativas de foco amplio para el español de Buenos Aires. La descripción cuantitativa es la resultante de la aplicación del modelo de superposición de contornos de frecuencia fundamental propuesto por Fujisaki (2003) para diversas lenguas. La descripción fonética que utiliza la marcación de índices de juntura y tono ToBI (Beckman y Ayers, 1993) surge de la percepción de los grupos entonativos y de las prominencias y la aplicación de un método de etiquetado manual (Gurlekian y otros, 2001b), denominado ToBI ampliado (ToBIA). Los resultados obtenidos, extienden la validez del modelo analítico para un gran número de oraciones declarativas de foco amplio del español. Asimismo se comprueba la validez del ToBI-A para producir un contorno de entonación comparable con el real a partir de las nuevas etiquetas propuestas. Para este fin, se realiza una prueba perceptual de comparación por pares y se calculan los errores respecto de la curva real que resultan ser del mismo orden para ambos modelos. También se verifica la validez del ToBI-A en las aplicaciones de síntesis de habla y para la definición fonológica de los acentos tonales de variedades no estudiadas del español

Revealing protein-lncRNA interaction

Long non-coding RNAs (lncRNAs) are associated to a plethora of cellular functions, most of which require the interaction with one or more RNA-binding proteins (RBPs); similarly, RBPs are often able to bind a large number of different RNAs. The currently available knowledge is already drawing an intricate network of interactions, whose deregulation is frequently associated to pathological states. Several different techniques were developed in the past years to obtain protein-RNA binding data in a high-throughput fashion. In parallel, in silico inference methods were developed for the accurate computational prediction of the interaction of RBP-lncRNA pairs. The field is growing rapidly, and it is foreseeable that in the near future, the protein-lncRNA interaction network will rise, offering essential clues for a better understanding of lncRNA cellular mechanisms and their disease-associated perturbations

Renewable Energy in Eastern North Africa in Terms of Patterns of Coupling to Czisch European HVDC Super Grid

In this study, wind energy potential and perspectives in the eastern North Africa region (Tunisia) have been investigated in terms of connectivity to the projected Czisch European HVDC super grid. A simplified extracted scheme of this grid has been used as a guide to optimize transportation efficiency through the whole net. Wind, as an available and easily exploitable renewable energy was showing to have a promising future for 2025 horizon in the context of a connected net with the European Union, despite local sub-grids disparities. This is also to emphasis HVDC technology adequacy for economical power transmission over very long distances andconnection between differently established grids

MicroRNAs from saliva of anopheline mosquitoes mimic human endogenous miRNAs and may contribute to vector-host-pathogen interactions

During blood feeding haematophagous arthropods inject into their hosts a cocktail of salivary proteins whose main role is to counteract host haemostasis, inflammation and immunity. However, animal body fluids are known to also carry miRNAs. To get insights into saliva and salivary gland miRNA repertoires of the African malaria vector Anopheles coluzzii we used small RNA-Seq and identified 214 miRNAs, including tissue-enriched, sex-biased and putative novel anopheline miRNAs. Noteworthy, miRNAs were asymmetrically distributed between saliva and salivary glands, suggesting that selected miRNAs may be preferentially directed toward mosquito saliva. The evolutionary conservation of a subset of saliva miRNAs in Anopheles and Aedes mosquitoes, and in the tick Ixodes ricinus, supports the idea of a non-random occurrence pointing to their possible physiological role in blood feeding by arthropods. Strikingly, eleven of the most abundant An. coluzzi saliva miRNAs mimicked human miRNAs. Prediction analysis and search for experimentally validated targets indicated that miRNAs from An. coluzzii saliva may act on host mRNAs involved in immune and inflammatory responses. Overall, this study raises the intriguing hypothesis that miRNAs injected into vertebrates with vector saliva may contribute to host manipulation with possible implication for vector-host interaction and pathogen transmission

Necroptosis in intestinal inflammation and cancer: new concepts and therapeutic perspectives

Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis plays a role in many disease conditions and inhibiting necroptosis is currently considered a promising therapeutic strategy. In this review, we focus on the molecular mechanisms of necroptosis as well as its involvement in human diseases. We also discuss the present developing therapies that target necroptosis machinery

Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-a)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1ß, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1ß and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria

Characterization of the lncRNA transcriptome in mESC-derived motor neurons: Implications for FUS-ALS

Long non-coding RNAs (lncRNAs) are currently recognized as crucial players in nervous system development, function and pathology. In Amyotrophic Lateral Sclerosis (ALS), identification of causative mutations in FUS and TDP-43 or hexanucleotide repeat expansion in C9ORF72 point to the essential role of aberrant RNA metabolism in neurodegeneration. In this study, by taking advantage of an in vitro differentiation system generating mouse motor neurons (MNs) from embryonic stem cells, we identified and characterized the long non-coding transcriptome of MNs. Moreover, by using mutant mouse MNs carrying the equivalent of one of the most severe ALS-associated FUS alleles (P517L), we identified lncRNAs affected by this mutation. Comparative analysis with humanMNs derived in vitro frominduced pluripotent stemcells indicated that candidate lncRNAs are conserved between mouse and human. Our work provides a global view of the long non-coding transcriptome of MN, as a prerequisite toward the comprehension of the still poorly characterized non-coding side ofMNphysiopatholog

Zooming in on protein–RNA interactions: a multilevel workflow to identify interaction partners

Interactions between proteins and RNA are at the base of numerous cellular regulatory and functional phenomena. The investigation of the biological relevance of non-coding RNAs has led to the identification of numerous novel RNA-binding proteins (RBPs). However, defining the RNA sequences and structures that are selectively recognised by an RBP remains challenging, since these interactions can be transient and highly dynamic, and may be mediated by unstructured regions in the protein, as in the case of many non-canonical RBPs. Numerous experimental and computational methodologies have been developed to predict, identify and verify the binding between a given RBP and potential RNA partners, but navigating across the vast ocean of data can be frustrating and misleading. In this mini-review, we propose a workflow for the identification of the RNA binding partners of putative, newly identified RBPs. The large pool of potential binders selected by in-cell experiments can be enriched by in silico tools such as catRAPID, which is able to predict the RNA sequences more likely to interact with specific RBP regions with high accuracy. The RNA candidates with the highest potential can then be analysed in vitro to determine the binding strength and to precisely identify the binding sites. The results thus obtained can furthermore validate the computational predictions, offering an all-round solution to the issue of finding the most likely RNA binding partners for a newly identified potential RBP