86,921 research outputs found

    Order and randomness in Kolmogorov–Johnson–Mehl–Avrami-type phase transitions

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    The distribution of points on a 2D domain influences the kinetics of its coverage when a growth law is attached at each point. This implies that the kinetics of space filling can be adopted as a descriptor of the degree of order of the initial point distribution. In this paper, the degree of order of an initial array of points has been changed following two paths: (i) from a regular square lattice, through increasing displacement assigned to each point, towards Poissonian disorder; (ii) from a Poissonian distribution, by introducing a hard core potential with increasing correlation lengths, towards a more ordered lattice. A linear growth law has been attached to the points of the initial array and the kinetics X.Xe/, where Xe is the extended coverage as defined in the Kolmogorov–Johnson–Mehl–Avrami model, has been monitored. The quantitative analysis has been performed by fitting the kinetics to an equation which we propose for the first time and which has proved to be, in fact, highly suitable for the purpose. The results demonstrate that the gross of variation from order to disorder is obtained for point displacements, u, of the order of a, the latter being the constant of a square lattice. Vice versa, the introduction of a correlation distance in a random distribution provokes at most an order limited to the first neighbors and no real order can ever be reached. Others descriptors have been investigated, all confirming our results. We also developed an analytical description based on the use of the f -functions, as have been defined by Van Kampen, up to the second order terms. Such a description has been shown to work well for u=a < 1 within an interval 1Xe which depends on the value

    LORENZ MAYCHER, Organ MASTERS RECITAL Sunday, April 23, 1989 5:00 p.m. at First Presbyterian Church

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    Playlist: Praeludium and fugue in E minor, BuxWV 142 / Dietrich Buxtehude (1637-1707) -- Nun komm der Heiden Heiland, BWV 659, BWV 660, and BWv 661 / Johann Sebastian Bach (1685-1750) -- Sonata no. 1 in F minor, op. 65 / Felix Mendelssohn-Bartholdy (1809-1847) -- Symphonie de la Passion, op. 20. 2. Le Tumulte au Prétoire / Paul de Maleingreu -- Chorale prelude : Drop, drop slow tears / Vincent Persichetti (1915-1987) -- Prelude and fugue in C major, op. 36, no. 3 / Marcel Dupré (1886-1971).This recital is given in partial fulfillment of the requirements for the Master of Music degree

    Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs

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    AbstractMammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation. Among well-established techniques (codon optimization and improvement of mRNA secondary structure), we describe SINEUPs, a family of antisense long non-coding RNAs that are able to increase translation of partially overlapping protein-coding mRNAs. By exploiting their modular structure, SINEUP molecules can be designed to target virtually any mRNA of interest, and thus to increase the production of secreted proteins. Thus, synthetic SINEUPs represent a new versatile tool to improve the production of secreted proteins in biomanufacturing processes

    The RNA-binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs

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    Transposable elements (TEs) compose about half of the mammalian genome and, as embedded sequences, up to 40% of long noncoding RNA (lncRNA) transcripts. Embedded TEs may represent functional domains within lncRNAs, providing a structured RNA platform for protein interaction. Here we show the interactome profile of the mouse inverted short interspersed nuclear element (SINE) of subfamily B2 (invSINEB2) alone and embedded in antisense (AS) ubiquitin C-terminal hydrolase L1 (Uchl1), an lncRNA that is AS to Uchl1 gene. AS Uchl1 is the representative member of a functional class of AS lncRNAs, named SINEUPs, in which the invSINEB2 acts as effector domain (ED)–enhancing translation of sense protein-coding mRNAs. By using RNA-interacting domainome technology, we identify the IL enhancer-binding factor 3 (ILF3) as a protein partner of AS Uchl1 RNA. We determine that this interaction is mediated by the RNA-binding motif 2 of ILF3 and the invSINEB2. Furthermore, we show that ILF3 is able to bind a free right Arthrobacter luteus (Alu) monomer sequence, the embedded TE acting as ED in human SINEUPs. Bioinformatic analysis of Encyclopedia of DNA Elements–enhanced cross-linking immunoprecipitation data reveals that ILF3 binds transcribed human SINE sequences at transcriptome-wide levels. We then demonstrate that the embedded TEs modulate AS Uchl1 RNA nuclear localization to an extent moderately influenced by ILF3. This work unveils the existence of a specific interaction between embedded TEs and an RNA-binding protein, strengthening the model of TEs as functional modules in lncRNAs.—Fasolo, F., Patrucco, L., Volpe, M., Bon, C., Peano, C., Mignone, F., Carninci, P., Persichetti, F., Santoro, C., Zucchelli, S., Sblattero, D., Sanges, R., Cotella, D., Gustincich, S. The RNA-binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs

    Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

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    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediatingmHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHttdependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment

    LESS is more: code-based signatures without syndromes

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    Devising efficient and secure signature schemes based on coding theory is still considered a challenge by the cryptographic community. In this paper, we construct a signature scheme by exploring a new approach to the area. To do this, we design a zero-knowledge identification scheme, which we then render static via standard means (e.g. Fiat-Shamir). We show that practical instances of our protocol have the potential to outperform the state of the art on code-based signatures, achieving small data sizes with a low computational complexity

    Post-operative course after papilloma resection: effects of written disclosure of the experience in subject with different alexithymia levels

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    Objective: The aim of the investigation was to assess the effects on post-operative course after bladder papilloma resection of a technique for the written disclosure of traumatic events, in interaction with individual differences in alexithymia. Method: 40 Ss. were administered a general questionnaire and the Toronto Alexithymia Scale (TAS-20) the second day after admittance. 20 Ss. were asked to write for 3 days, 20 minutes a day, about their experience of being in hospital, following instructions developed by J.W. Pennebaker and co-workers. The post-operative course was assessed objectively by the duration of stay in hospital and subjectively by Ss. completing the Symptom Check List 90 (SCL 90) the day before leaving hospital. Results: Ss. who wrote stayed fewer days in hospital and showed lower SCL 90 scores. The same effect was shown by low alexithymia levels. Study of interactions showed that the effect of writing was apparent only in Ss. high in alexithymia, while Ss. low in alexithymia showed a favourable course independent of writing. Conclusions: Writing about one's thoughts and feelings about being in hospital for a surgical operation shows beneficial effects on post-operative course. This holds particularly true for high alexithymic Ss., who obtain through writing the same outcome as low alexithymic Ss

    Morphological and electronic characterization of functionalized graphene nanoribbons obtained by the unzipping of single-wall carbon nanotubes: A Scanning Tunneling Microscopy study

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    A few layers of functionalized graphene (FLG) have been obtained by the oxidative unzipping reaction of single-walled carbon nanotubes. A detailed Scanning Tunneling Microscopy and Transmission Electron Microscopy study shows that several different morphologies are observed, depending on the substrate upon which they are deposited, thus providing useful hints for a real world application of these carbon nanostructures. In addition, a combined Scanning Tunneling Spectroscopy investigation has shown that the electronic properties of these FLG are affected by their functionalization degree, opening interesting perspectives for their use in sensor and biosensor devices. © Taylor & Francis Group, LLC

    Structural Properties of Polyglutamine Aggregates Investigated via Molecular Dynamics Simulations

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    Polyglutamine (polyQ) beta-stranded aggregates constitute the hallmark of Huntington disease. The disease is fully penetrant when Q residues are more than 36-40 ("disease threshold"). Here, based on a molecular dynamics study on polyQ helical structures of different shapes and oligomeric states, we suggest that the stability of the aggregates increases with the number of monomers, while it is rather insensitive to the number of Qs in each monomer. However, the stability of the single monomer does depend on the number of side-chain intramolecular H-bonds, and therefore oil the number of Qs. If such number is lower than that of the disease threshold, the beta-stranded monomers are unstable and hence may aggregate with lower probability, consistently with experimental findings. Our results provide a possible interpretation of the apparent polyQ length dependent-toxicity, and they do not support the so-called "structural threshold hypothesis", which supposes a transition from random coil to a beta-sheet structure only above the disease threshold
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