Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Lambda beta (amyloid beta-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to A beta accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

Recognition of double helical DNA by purine oligonucleotides via triple helix formation

Oligonucleotide-directed triple helix formation is one of the most versatile methods for the sequence specific recognition of double helical DNA. Chapter 2 describes affinity cleaving experiments carried out to assess the recognition potential for purine-rich oligonucleotides via the formation of triple helices. Purine-rich oligodeoxyribonucleotides were shown to bind specifically to purine tracts of double helical DNA in the major groove antiparallel to the purine strand of the duplex. Specificity was derived from the formation of reverse Hoogsteen G•GC, A•AT and T•AT triplets and binding was limited to mostly purine tracts. This triple helical structure was stabilized by multivalent cations, destabilized by high concentrations of monovalent cations and was insensitive to pH. A single mismatched base triplet was shown to destabilize a 15 mer triple helix by 1.0 kcal/mole at 25°C. In addition, stability appeared to be correlated to the number of G•GC triplets formed in the triple helix. This structure provides an additional framework as a basis for the design of new sequence specific DNA binding molecules.

In work described in Chapter 3, the triplet specificities and required strand orientations of two classes of DNA triple helices were combined to target double helical sequences containing all four base pairs by alternate strand triple helix formation. This allowed for the use of oligonucleotides containing only natural 3'-5' phosphodiester linkages to simultaneously bind both strands of double helical DNA in the major groove. The stabilities and structures of these alternate strand triple helices depended on whether the binding site sequence was 5'-(purine)_m (pyrimidine)_n-3' or 5'- (pyrimidine)_m (purine)_n-3'.

In Chapter 4, the ability of oligonucleotide-cerium(III) chelates to direct the transesterfication of RNA was investigated. Procedures were developed for the modification of DNA and RNA oligonucleotides with a hexadentate Schiff-base macrocyclic cerium(III) complex. In addition, oligoribonucleotides modified by covalent attachment of the metal complex through two different linker structures were prepared. The ability of these structures to direct transesterification to specific RNA phosphodiesters was assessed by gel electrophoresis. No reproducible cleavage of the RNA strand consistent with transesterification could be detected in any of these experiments.

Studies of Zγ production and constraints on anomalous triple gauge couplings in pp collisions at √s = 7 TeV

In this thesis, we test the electroweak sector of the Standard Model of particle physics through the measurements of the cross section of the simultaneous production of the neutral weak boson Z and photon γ, and the limits on the anomalous Zγγ and ZZγ triple gauge couplings h3 and h4 with the Z decaying to leptons (electrons and muons). We analyze events collected in proton-proton collisions at center of mass energy of sqrt(s) = 7 TeV corresponding to an integrated luminosity of 5.0 inverse femtobarn. The analyzed events were recorded by the Compact Muon Solenoid detector at the Large Hadron Collider in 2011.

The production cross section has been measured for hard photons with transverse momentum greater than 15 GeV that are separated from the the final state leptons in the eta-phi plane by Delta R greater than 0.7, whose sum of the transverse energy of hadrons over the transverse energy of the photon in a cone around the photon with Delta R less than 0.3 is less than 0.5, and with the invariant mass of the dilepton system greater than 50 GeV. The measured cross section value is 5.33 +/- 0.08 (stat.) +/- 0.25 (syst.) +/- 0.12 (lumi.) picobarn. This is compatible with the Standard Model prediction that includes next-to-leading-order QCD contributions: 5.45 +/- 0.27 picobarn.

The measured 95 % confidence-level upper limits on the absolute values of the anomalous couplings h3 and h4 are 0.01 and 8.8E-5 for the Zγγ interactions, and, 8.6E-3 and 8.0E-5 for the ZZγ interactions. These values are also compatible with the Standard Model where they vanish in the tree-level approximation. They extend the sensitivity of the 2012 results from the ATLAS collaboration based on 1.02 inverse femtobarn of data by a factor of 2.4 to 3.1.

Utilización del Modelo de Triple Hélice para el desarrollo de nuevos sectores productivos en el contexto de la Industria 4.0

Máster en Dirección Empresarial desde la Innovación y la Internacionalización. Curso 2014/2015

Analysis of the energies of the triple base triplets

Sixty-four sets of three-dimensional models of DNA triplex base triplets (TBT) were built up based on codons by homologous modeling method and their energies were minimized. According to sequence of TBT and orientation of the third ODN strand third, the energies of monomers and water-K+-TBT ternary complexes of TBT were analyzed. The results showed: (i) The energies of the symmetric parallel monomers are generally lower than those of the symmetric anti-parallel monomers of TBT, but the energies of the symmetric parallel ternary complexes are higher than those of the symmetric anti-parallel ternary complexes of TBT. (ii) No matter TBTs are monomers or ternary complexes, the energies of asymmetric parallel TBTs are generally lower than those of the asymmetric anti-parallel ones. (iii) Although the energies of the parallel TBTs are correlated with those of the anti-parallel ones, the energy differences are significant between them. The results here suggest the sequences of TBTs and the orientations of the third ODN strands are two of the key factors that can influence the formation and stability of TBT. (C) 2002 Elsevier Science B.V. All rights reserved.

The comparative analysis of the energies of conjugated triple base triplets and their applications

We built 64 sets of 3D models of DNA triplex base triplets (TBT) and minimized their energies. The TBTs were divided into 32 pairs of conjugated ones on the basis of their sequence characteristic, and the energies of each pair of them were compared and analyzed, the results showed: (i) The duplex DNA of which any strand contains at least a couple of A or T, has a preference for selecting the oligodeoxyribonucleic acid (ODN) strand containing abundant T to form TBT. (ii) The duplex DNA of which any strand contains at least a couple of G or C has a preference for selecting ODN containing abundant G to form symmetric antiparallel TBT, but selecting ODN containing abundant C to form asymmetric parallel TBT. (iii) The duplex DNA of which any strand contains only one of A, T, G or C has a preference for selecting ODN containing abundant pyrimidines (T or C) to form antiparallel TBT. Additionally, two examples of TBTs applications, in designing ODN to form triplex with duplex were presented. The energy calculation result revealed that 15-TCG is the best ligand of the HIV PPT duplex. The comparative analysis of energies of the conjugated TBTs provides directive significance for designing ODN strand that is easy to form triplex in theory. (C) 2002 Elsevier Science B.V. All rights reserved.

A framework for clarifying the meaning of Triple Bottom-Line, Integrated, and Sustainability Assessment

Terms such as Integrated Assessment and Sustainability Assessment are used to label 'new' approaches to impact assessment that are designed to direct planning and decision-making towards sustainable development (SD). Established assessment techniques, such as EIA and SEA, are also widely promoted as SD 'tools'. This paper presents the findings of a literature review undertaken to identify the features that are typically promoted for improving the SD-directedness of assessments. A framework is developed which reconciles the broad range of emerging approaches and tackles the inconsistent use of terminology. The framework comprises a three-dimensional space defined by the following axes: the comprehensiveness of the SD coverage; the degree of 'integration' of the techniques and themes; and the extent to which a strategic perspective is adopted. By applying the framework, assessment approaches can be positioned relative to one another, enabling comparison on the basis of substance rather than semantics. © 2007 Elsevier Inc. All rights reserved.

Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy.

The role of the collagen-platelet interaction is of crucial importance to the haemostatic response during both injury and pathogenesis of the blood vessel wall. Of particular interest is the high affinity interaction of the platelet transmembrane receptor, alpha 2 beta 1, responsible for firm attachment of platelets to collagen at and around injury sites. We employ single molecule force spectroscopy (SMFS) using the atomic force microscope (AFM) to study the interaction of the I-domain from integrin alpha 2 beta 1 with a synthetic collagen related triple-helical peptide containing the high-affinity integrin-binding GFOGER motif, and a control peptide lacking this sequence, referred to as GPP. By utilising synthetic peptides in this manner we are able to study at the molecular level subtleties that would otherwise be lost when considering cell-to-collagen matrix interactions using ensemble techniques. We demonstrate for the first time the complexity of this interaction as illustrated by the complex multi-peaked force spectra and confirm specificity using control blocking experiments. In addition we observe specific interaction of the GPP peptide sequence with the I-domain. We propose a model to explain these observations.

Linking business ecosystem lifecycle with platform strategy: A triple view of technology, application and organisation

This paper explores platform strategies along the business ecosystem lifecycle (BELC), based on a multiple-case study. Developing observations on platform strategies from a firm level to a business ecosystem level, the study investigates the issue of platform strategy through three views, respectively technology, application and organisation. As a result, a general evolutional pattern of platform strategy along the BELC is identified, where an open strategy emerges at the birth and expansion phases, then a dominating strategy rises at the authority phase, and finally the opportunistic strategy takes over at the renewal phase. This paper connects the core firms in the business ecosystem with the evolutionary platform strategies. Copyright © 2013 Inderscience Enterprises Ltd.

An Arbitrary Lagrangian Eulerian Method for Three-Phase Flows with Triple Junction Points

We present a moving mesh method suitable for solving two-dimensional and axisymmetric three-liquid flows with triple junction points. This method employs a body-fitted unstructured mesh where the interfaces between liquids are lines of the mesh system, and the triple junction points (if exist) are mesh nodes. To enhance the accuracy and the efficiency of the method, the mesh is constantly adapted to the evolution of the interfaces by refining and coarsening the mesh locally; dynamic boundary conditions on interfaces, in particular the triple points, are therefore incorporated naturally and accurately in a Finite- Element formulation. In order to allow pressure discontinuity across interfaces, double-values of pressure are necessary for interface nodes and triple-values of pressure on triple junction points. The resulting non-linear system of mass and momentum conservation is then solved by an Uzawa method, with the zero resultant condition on triple points reinforced at each time step. The method is used to investigate the rising of a liquid drop with an attached bubble in a lighter liquid.