6,248 research outputs found
Some Remarks on a Generalized Vector Product
In this paper we use a generalized vector product to construct an exterior
form , where
, . Finally, for we
introduce the reversing operation to study this generalized vector product over
palindromic and antipalindromic vectors.Comment: 10 pages, 14 pages in the published version: Revista Integraci\'o
Characterisation of the MID1/α4 multiprotein complex
Opitz BBB/G syndrome (OS) is a congenital disorder characterised by malformations of the ventral midline, with hypertelorism and hypospadias being the two cardinal phenotypic manifestations. OS is genetically heterogeneous, with an autosomal and an X-linked locus. While the gene at the autosomal locus remains to be identified, the X-chromosomal form has been shown to be caused by mutations in the MID1 gene, which harbours mutations in approximately 68% of patients with X-linked OS. Most of the mutations identified in OS patients are located at the 3âČ end of the MID1 open reading frame, thus affecting the C-terminus of the The MID1 protein belongs to the RFP subfamily of the RBCC family of proteins. At its Nterminal end it contains a RING finger, two Bboxes (Bbox1, Bbox2), and a coiled-coil domain (RBCC domain), which are followed by a FNIII domain and a B30.2 domain (RFP domain) at its C-terminal end. MID1 has been shown to form macromolecular cellular complexes, the components of which were, up to now, mainly unknown. Similar to other RBCC proteins, MID1 contains several putative protein-protein interaction domains. Recently, we have shown that the C-terminally microtubule-associated MID1 protein binds α4, a regulatory subunit of phosphatase 2A (PP2A), through the Bbox1 domain, thereby targeting the catalytic subunit of microtubuleassociated PP2A (PP2Ac) towards ubiquitin-specific modification and degradation. MID1 mutations in the C-terminal end of the protein lead to disruption of microtubule association of MID1 and subsequent formation of clumps in the cytosol. Despite preserving its association with α4, C-terminally mutated MID1 can not approach the vicinity of microtubule-associated PP2Ac and, therefore, the ubiquitination and degradation of microtubule-associated PP2Ac becomes During this thesis, basic functions of Bbox1 and Bbox2, with respect to MID1-α4 and MID1-microtubule interactions, were studied in detail by immunofluorescence, immunoprecipitation and yeast two-hybrid experiments. In this way, a novel pathomechanism for OS could be identified based on mutations in Bbox1 or Bbox2 domains of MID1 rather than C-terminal mutations. While the Bbox1 was shown to be responsible for the interaction of MID1 with α4, the Bbox2 was demonstrated to act as a regulatory arm that couples the MID1 ubiquitin ligase function to the microtubules by regulating the association of MID1 with both α4 and As the main focus of this thesis, the MID1 multiprotein complex was elucidated via affinity chromatography and mass spectrometry. Besides tubulin association, which has previously been reported, MID1 was shown to associate with several proteins of the small ribosomal subunit (S3, S8, p40) and other multifunctional proteins such as NPM, RACK1 and ANXA2, which also associate with ribosomes and RNA. In addition, heat shock proteins, such as Hsp60, Hsc70, and the multifunctional chaperones Hsp90 and p32, were identified in the complex. Through further characterisation of the MID1 protein complex, it could be demonstrated during this thesis that the MID1 protein, together with the mTOR target α4, forms a microtubuleassociated mRNP that contains active polyribosomes and RNA, and thus links the translation regulatory mTOR pathway with a microtubule-associated translation unit. This complex is likely to participate in the transport of mRNAs to the poles of the cell, providing asymmetric mRNA localisation and protein production. Compartmentalised protein translation is an important prerequisite for neural crest cells to migrate and polarised cells to step into epithelialmesenchymal transition, both essential processes during ventral midline development. Therefore, the results of this thesis suggest a molecular basis for both the development of the ventral midline and the pathogenesis of OS. Moreover, it could be shown that the MID1/α4 complex integrates mRNAs of ephrinB molecules (ligands and receptors) through G-quartet structures located in their 3ÂŽUTRs. Ephrins and Eph receptors participate in the regulation of essential processes during the development of the ventral midline, such as cell attachment, cell migration and embryonic patterning. Therefore, this thesis suggests a central role for the MID1/α4 protein complex in the microtubuleassociated compartmentalised translation of EphB receptors and ephrins-B. Interaction of the MID1 protein complex with the mRNA of ephrin-B1 (EFNB1) is of particular interest since mutated EFNB1 leads to the development of craniofrontonasal dysplasia, a monogenic disorder with manifestations that are highly reminiscent of the OS phenotype. Consequently, the model proposed here also provides an attractive explanation for the conspicuous phenotypic overlap of the two disorders
Multicomponent bionanocomposites based on clay nanoarchitectures for electrochemical devices
Based on the unique ability of defibrillated sepiolite (SEP) to form stable and homogeneous colloidal dispersions of diverse types of nanoparticles in aqueous media under ultrasonication, multicomponent conductive nanoarchitectured materials integrating halloysite nanotubes (HNTs), graphene nanoplatelets (GNPs) and chitosan (CHI) have been developed. The resulting nanohybrid suspensions could be easily formed into films or foams, where each individual component plays a critical role in the biocomposite: HNTs act as nanocontainers for bioactive species, GNPs provide electrical conductivity (enhanced by doping with MWCNTs) and, the CHI polymer matrix introduces mechanical and membrane properties that are of key significance for the development of electrochemical devices. The resulting characteristics allow for a possible application of these active elements as integrated multicomponent materials for advanced electrochemical devices such as biosensors and enzymatic biofuel cells. This strategy can be regarded as an "a la carte" menu, where the selection of the nanocomponents exhibiting different properties will determine a functional set of predetermined utility with SEP maintaining stable colloidal dispersions of different nanoparticles and polymers in water
The Odyssey Approach for Optimizing Federated SPARQL Queries
Answering queries over a federation of SPARQL endpoints requires combining
data from more than one data source. Optimizing queries in such scenarios is
particularly challenging not only because of (i) the large variety of possible
query execution plans that correctly answer the query but also because (ii)
there is only limited access to statistics about schema and instance data of
remote sources. To overcome these challenges, most federated query engines rely
on heuristics to reduce the space of possible query execution plans or on
dynamic programming strategies to produce optimal plans. Nevertheless, these
plans may still exhibit a high number of intermediate results or high execution
times because of heuristics and inaccurate cost estimations. In this paper, we
present Odyssey, an approach that uses statistics that allow for a more
accurate cost estimation for federated queries and therefore enables Odyssey to
produce better query execution plans. Our experimental results show that
Odyssey produces query execution plans that are better in terms of data
transfer and execution time than state-of-the-art optimizers. Our experiments
using the FedBench benchmark show execution time gains of at least 25 times on
average.Comment: 16 pages, 10 figure
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Putting medical devices in context: a systematic review of evidence on design targeting low-resource settings
Most medical devices are inaccessible to healthcare facilities in low-resource settings (LRSs), severely limiting medical care for a vast proportion of the world's population. This article characterises the process used for designing medical devices for LRSs and investigate how the context-of-use is integrated into the process. A systematic review of 64 papers was conducted to identify peer-reviewed studies of devices intended for LRSs. Using the biodesign process as an analytic framework, a qualitative meta-analysis was conducted. Findings show the studies predominantly describe the later stages of medical device design, whilst largely neglecting how knowledge of the context is considered. To support engineers and improve outcomes, it is imperative that an understanding of the context is integrated throughout the design and product development process. This article highlights this gap and hopes to stimulate research into how context can be better incorporated into the design process for medical devices targeting those populations most in need.This is the author accepted manuscript. The final version is available from Inderscience Publishers via http://dx.doi.org/10.1504/IJDE.2015.07637
Synthetizing Qualitative (Logical) Patterns for Pedestrian Simulation from Data
This work introduces a (qualitative) data-driven framework
to extract patterns of pedestrian behaviour and synthesize Agent-Based
Models. The idea consists in obtaining a rule-based model of pedestrian
behaviour by means of automated methods from data mining. In order to
extract qualitative rules from data, a mathematical theory called Formal
Concept Analysis (FCA) is used. FCA also provides tools for implicational
reasoning, which facilitates the design of qualitative simulations
from both, observations and other models of pedestrian mobility. The
robustness of the method on a general agent-based setting of movable
agents within a grid is shown.Ministerio de EconomĂa y Competitividad TIN2013-41086-
Towards a Soft Evaluation and Refinement of Tagging in Digital Humanities
In this paper we estimate the soundness of tagging in digital repositories
within the field of Digital Humanities by studying the (semantic) conceptual structure
behind the folksnonomy. The use of association rules associated to this conceptual
structure (Stem and Luxenburger basis) allows to faithfully (from a semantic
point of view) complete the tagging (or suggest such a completion).Ministerio de EconomĂa y Competitividad TIN2013-41086-PJunta de AndalucĂa TIC-606
A new method for the solution of the Schrodinger equation
We present a new method for the solution of the Schrodinger equation
applicable to problems of non-perturbative nature. The method works by
identifying three different scales in the problem, which then are treated
independently: An asymptotic scale, which depends uniquely on the form of the
potential at large distances; an intermediate scale, still characterized by an
exponential decay of the wave function and, finally, a short distance scale, in
which the wave function is sizable. The key feature of our method is the
introduction of an arbitrary parameter in the last two scales, which is then
used to optimize a perturbative expansion in a suitable parameter. We apply the
method to the quantum anharmonic oscillator and find excellent results.Comment: 4 pages, 4 figures, RevTex
Constraints on Natural MNS Parameters from |U_e3|
The MNS matrix structure emerging as a result of recent neutrino measurements
strongly suggests two large mixing angles (solar and atmospheric) and one small
angle (|U_e3| << 1). Especially when combined with the neutrino mass hierarchy,
these values turn out to impose rather stringent constraints on possible flavor
models connecting the three active fermion generations. Specifically, we show
that an extremely small value of |U_e3| would require fine tuning of Majorana
mass matrix parameters, particularly in the context of seesaw models.Comment: 21 pages, ReVTeX, 2 .eps figure files, updated references and
acknowledgment
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