Distributed all-atom simulations of intrinsically unstructured proteins

The Computational Biophysics Group at the Universitat Pompeu Fabra (GRIB-UPF) hosts two unique computational resources dedicated to the execution of large scale molecular dynamics (MD) simulations: (a) the ACMD molecular-dynamics software, used on standard personal computers with graphical processing units (GPUs); and (b) the GPUGRID. net computing network, supported by users distributed worldwide that volunteer GPUs for biomedical research. We leveraged these resources and developed studies, protocols and open-source software to elucidate energetics and pathways of a number of biomolecular systems, with a special focus on flexible proteins with many degrees of freedom. First, we characterized ion permeation through the bactericidal model protein Gramicidin A conducting one of the largest studies to date with the steered MD biasing methodology. Next, we addressed an open problem in structural biology, the determination of drug-protein association kinetics; we reconstructed the binding free energy, association, and dissaciociation rates of a drug like model system through a spatial decomposition and a Makov-chain analysis. The work was published in the Proceedings of the National Academy of Sciences and become one of the few landmark papers elucidating a ligand-binding pathway. Furthermore, we investigated the unstructured Kinase Inducible Domain (KID), a 28-peptide central to signalling and transcriptional response; the kinetics of this challenging system was modelled with a Markovian approach in collaboration with Frank Noe’s group at the Freie University of Berlin. The impact of the funding includes three peer-reviewed publication on high-impact journals; three more papers under review; four MD analysis components, released as open-source software; MD protocols; didactic material, and code for the hosting group.

21st century climate change: where has all the geomorphology gone?

This Commentary draws together recently published work relating to the relationship between climate change and geomorphology to address the surprising observation that geomorphic work seems to have had little impact upon the work of the Intergovernmental Panel for Climate Change. However, recent papers show that methodological innovation has allowed geomorphological reconstruction over timescales highly relevant to late 20th century and 21st century climate change. In turn, these and other developments are allowing links to be made between climatic variability and geomorphology, to begin to predict geomorphic futures and also to appreciate the role that geomorphic processes play in the flux of carbon and the carbon cycle.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Background: Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results: Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion:This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.

Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (IRRAs Project)

Background and purpose: Individual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research. Methods: A specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C(10), C(01), C(11)) Mooney-Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status.Results: Tissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture. Conclusion: There is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making.

A systolic array for linear MIMO detection based on an all-swap lattice reduction algorithm

A systolic array to implement lattice-reduction-aided lineardetection is proposed for a MIMO receiver. The lattice reductionalgorithm and the ensuing linear detections are operated in the same array, which can be hardware-efficient. All-swap lattice reduction algorithm (ASLR) is considered for the systolic design.ASLR is a variant of the LLL algorithm, which processes all lattice basis vectors within one iteration. Lattice-reduction-aided linear detection based on ASLR and LLL algorithms have very similarbit-error-rate performance, while ASLR is more time efficient inthe systolic array, especially for systems with a large number ofantennas.

Conquiste della Serenissima Republica di Venetia nella Moreasotto il comando del doge Francesco Morosini / Descritte, e dedicate all illustrissimo et eccellentissimo signore il signore Domenico Contarini, ... ; Alla Santità di N. S. Innocenzo XII ; Dal Padre Cosmografo Coronelli

Échelle(s) : [Echelles diverses]

Carmen Martín Gaite y el periodismo. La visión de los medios de comunicación en los artículos de prensa (1949-2000)

La escritora salmantina Carmen Martín Gaite (1925-2000) compaginó su dedicación a la novela con la publicación de casi trescientos artículos en la prensa durante la segunda mitad del siglo XX. Estos años corresponden al “lento desentumecerse de la España de la posguerra para desembocar en la de la televisión y el consumo”, en palabras de la propia autora.Este estudio pretende analizar la mirada de Martín Gaite sobre estos cambios comunicativos y sociales, a la vez que quiere abordar la vertiente periodística de la escritora, sólo estudiada hasta el momento por José Teruel. Partiremos de la hipótesis de que Carmen Martín Gaite revela en sus artículos una relación ambigua con los medios de comunicación: unas veces se muestra entusiasmada por el periodismo mientras que en otras ocasiones se trasluce una visión despectiva de los mass media, especialmente de los audiovisuales.

Els Colors : estratègia i imatge empresarial

L’estudi presentat en aquest informe correspon a la investigació al voltant del paper del color al màrqueting empresarial. La seva influència, ja sigui com a eina comunicativa o identificadora d’un producte o empresa, es torna molt superior a la qualse li podria atribuir en un primer moment (fins al punt de convertir-se en un aspecte clau) quan s’observa la reacció dels consumidors davant les seves variacions i l’aplicació que en fan les companyies.La primera idea a confirmar pel treball és el caràcter inconscient de les reaccions generades per la percepció visual i les motivacions existents per explotarles.Un estudi sobre els precursors i les teories actuals de la psicologia del color condueix a una comparació entre allò que reflecteixen els estudis amb la realitat empresarial actual, mostrant una correlació evident entre valors de les organitzacions iles seves expressions pictòriques i exemplificant situacions de coincidència entre canvi de color i canvi d’estratègia corporativa. Aquest procés dóna lloc a la hipòtesi principal: el color és un element indispensable del procés de comercialització.Per tal de contrastar-la, inicialment s’acudirà a l’evidència recaptada mitjançant un qüestionari d’elaboració pròpia. A partir dels seus resultats, observarem com els consumidors no creuen estar tan influenciats per l’estètica i el color dels productes que compren com efectivament ho estan, i podrem seguir reafirmant la teoria exposada a la primera part amb paral·lelismes respecte les opinions mostrades.A continuació, es reflexionarà sobre quatre funcions del color aplicades a l’empresa de les quals aquestes es poden beneficiar: segmentador de mercats, indicador de canvi de tendència, identificador nacional i element associatiu immediat.Les determinacions preses a cada apartat a partir de reflexions teòriques i exemples formaran un entramat de conclusions que posarà fi al projecte en un apartat en el quals’ordenen les bases per a la correcta aplicació del color al món empresarial, en funció del rol de la companyia dins del seu mercat, els valors a transmetre, el tipus de producte a comerciar, etc.Finalment, els nombrosos fonaments que se li poden atribuir a favor fan que lahipòtesi inicial quedi ratificada com a certa, ja que es demostrarà una permanent voluntat per part de les empreses d’influir sobre el comportament dels destinataris del seu procés publicitari mitjançant aquest recurs, ja sigui de manera directa o indirecta.