Kinematics and dynamic complexity of postural transitions in frail elderly subjects.

The aim of this study was to propose a methodology allowing a detailed characterization of body sit-to-stand/stand-to-sit postural transition. Parameters characterizing the kinematics of the trunk movement during sit-to-stand (Si-St) postural transition were calculated using one initial sensor system fixed on the trunk and a data logger. Dynamic complexity of these postural transitions was estimated by fractal dimension of acceleration-angular velocity plot. We concluded that this method provides a simple and accurate tool for monitoring frail elderly and to objectively evaluate the efficacy of a rehabilitation program.

A new training set-up for trans-apical aortic valve replacement.

Trans-apical aortic valve replacement (AVR) is a new and rapidly growing therapy. However, there are only few training opportunities. The objective of our work is to build an appropriate artificial model of the heart that can replace the use of animals for surgical training in trans-apical AVR procedures. To reduce the necessity for fluoroscopy, we pursued the goal of building a translucent model of the heart that has nature-like dimensions. A simplified 3D model of a human heart with its aortic root was created in silico using the SolidWorks Computer-Aided Design (CAD) program. This heart model was printed using a rapid prototyping system developed by the Fab@Home project and dip-coated two times with dispersion silicone. The translucency of the heart model allows the perception of the deployment area of the valved-stent without using heavy imaging support. The final model was then placed in a human manikin for surgical training on trans-apical AVR procedure. Trans-apical AVR with all the necessary steps (puncture, wiring, catheterization, ballooning etc.) can be realized repeatedly in this setting.

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

Exploring unfrequent events with accelerated molecular dynamics simulations: from photochemistry to drug design

La meva incorporació al grup de recerca del Prof. McCammon (University of California San Diego) en qualitat d’investigador post doctoral amb una beca Beatriu de Pinós, va tenir lloc el passat 1 de desembre de 2010; on vaig dur a terme les meves tasques de recerca fins al darrer 1 d’abril de 2012. El Prof. McCammon és un referent mundial en l’aplicació de simulacions de dinàmica molecular (MD) en sistemes biològics d’interès humà. La contribució més important del Prof. McCammon en la simulació de sistemes biològics és el desenvolupament del mètode de dinàmiques moleculars accelerades (AMD). Les simulacions MD convencionals, les quals estan limitades a l’escala de temps del nanosegon (~10-9s), no son adients per l’estudi de sistemes biològics rellevants a escales de temps mes llargues (μs, ms...). AMD permet explorar fenòmens moleculars poc freqüents però que son clau per l’enteniment de molts sistemes biològics; fenòmens que no podrien ser observats d’un altre manera. Durant la meva estada a la “University of California San Diego”, vaig treballar en diferent aplicacions de les simulacions AMD, incloent fotoquímica i disseny de fàrmacs per ordinador. Concretament, primer vaig desenvolupar amb èxit una combinació dels mètodes AMD i simulacions Car-Parrinello per millorar l’exploració de camins de desactivació (interseccions còniques) en reaccions químiques fotoactivades. En segon lloc, vaig aplicar tècniques estadístiques (Replica Exchange) amb AMD en la descripció d’interaccions proteïna-lligand. Finalment, vaig dur a terme un estudi de disseny de fàrmacs per ordinador en la proteïna-G Rho (involucrada en el desenvolupament de càncer humà) combinant anàlisis estructurals i simulacions AMD. Els projectes en els quals he participat han estat publicats (o estan encara en procés de revisió) en diferents revistes científiques, i han estat presentats en diferents congressos internacionals. La memòria inclosa a continuació conté més detalls de cada projecte esmentat.

Protein-ligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to HIV-1 protease inhibitors.

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. Conformational sampling of the protein-ligand complex is performed by molecular dynamics (MD) in vacuo and the solvent effect is calculated a posteriori by solving the Poisson or the Poisson-Boltzmann equation for selected frames of the trajectory. The binding free energy is written as a linear combination of the buried surface upon complexation, SASbur, the electrostatic interaction energy between the ligand and the protein, Eelec, and the difference of the solvation free energies of the complex and the isolated ligand and protein, deltaGsolv. The method uses the buried surface upon complexation to account for the non-polar contribution to the binding free energy because it is less sensitive to the details of the structure than the van der Waals interaction energy. The parameters of the method are developed for a training set of 16 HIV-1 protease-inhibitor complexes of known 3D structure. A correlation coefficient of 0.91 was obtained with an unsigned mean error of 0.8 kcal/mol. When applied to a set of 25 HIV-1 protease-inhibitor complexes of unknown 3D structures, the method provides a satisfactory correlation between the calculated binding free energy and the experimental pIC5o without reparametrization.

Investigation of high-resolution functional magnetic resonance imaging by means of surface and array radiofrequency coils at 7 T.

In this investigation, high-resolution, 1x1x1-mm(3) functional magnetic resonance imaging (fMRI) at 7 T is performed using a multichannel array head coil and a surface coil approach. Scan geometry was optimized for each coil separately to exploit the strengths of both coils. Acquisitions with the surface coil focused on partial brain coverage, while whole-brain coverage fMRI experiments were performed with the array head coil. BOLD sensitivity in the occipital lobe was found to be higher with the surface coil than with the head array, suggesting that restriction of signal detection to the area of interest may be beneficial for localized activation studies. Performing independent component analysis (ICA) decomposition of the fMRI data, we consistently detected BOLD signal changes and resting state networks. In the surface coil data, a small negative BOLD response could be detected in these resting state network areas. Also in the data acquired with the surface coil, two distinct components of the positive BOLD signal were consistently observed. These two components were tentatively assigned to tissue and venous signal changes.

Power supply noise and logic error probability

Voltage fluctuations caused by parasitic impedances in the power supply rails of modern ICs are a major concern in nowadays ICs. The voltage fluctuations are spread out to the diverse nodes of the internal sections causing two effects: a degradation of performances mainly impacting gate delays anda noisy contamination of the quiescent levels of the logic that drives the node. Both effects are presented together, in thispaper, showing than both are a cause of errors in modern and future digital circuits. The paper groups both error mechanismsand shows how the global error rate is related with the voltage deviation and the period of the clock of the digital system.

Manipulació geomètrica dels blocs d'AutoCAD

Aquest text és un recull de procediments per inserir els blocs d'AutoCAD de forma més eficient, en la resolució de problemes prèviament tipificats: la PRIMERA PART descriu protocols d'actuació que l'usuari haurà d'aplicar manualment, mentre que la SEGONA PART ofereix rutines programades en AutoLISP i VisualLISP que l'eximiran d'aquesta obligació.Si ho deixéssim aquí, però, podria semblar que els mateixos mètodes manuals presentats en primer lloc són després els que AutoLISP automatitza; per això convé aclarir que la problemàtica de la PRIMERA PART, tot i que pròxima a la de la SEGONA, és diferent i reprodueix el contingut d'una monografia (BLOCS I GEOMETRIA: 5 EXERCICIS COMENTATS) que forma part del material de suport a l'assignatura ELEMENTS DE CAD, impartida per l'autor en l'ETS d'Enginyeria de Telecomunicació de Barcelona i que té per objecte cobrir el buit bibliogràfic que es detectava en el vessant geomètric de la inserció de blocs, a diferència del que s'ocupa de l'estructura de dades més adient en cada context (incrustació de dibuixos amb INSERT versus vinculació mitjançant REFX), més profusament tractat, proposant una sistematització tipològica dels casos on l'escala és funció lineal d'una distància.La SEGONA PART va més enllà i amplia el repertori d'AutoCAD amb les ordres GINSERT, RATREDIT, INSERTOK, INS2D, INS3D, BLOQUEOK, DESCOMPOK, DEF-TRANSF, APL-TRANSF-V i APL-TRANSF-N, de les quals INS2D i INS3D (INSERTOK és una versió simplificada de INS2D, per a blocs sense atributs) són l'aportació més innovadora i que més lluny porta les potencialitats de la inserció de blocs: resumint-ho en una frase, es tracta d’aconseguir que la inserció d’un bloc (que pot ser l’original, un bloc constituït per una inserció de l’original o un de constituït per la inserció del precedent) s’encabeixi en un marc prèviament establert, a semblança de les ordres ESCALA o GIRA, que mitjançant l'opció Referencia apliquen als objectes seleccionats la transformació d'escalat o de rotació necessària per tal que un element de referència assoleixi una determinada grandària o posició. Tot i que, per identificar amb encert el nucli del problema, serà inevitable introduir una reflexió: quan s’ha tingut la precaució de referir un bloc 2D a un quadrat unitari ortogonal, inserir-lo de manera que s’adapti a qualsevol marc rectangular establert en el dibuix és immediat, però ja no ho és tant concatenar insercions de manera que, a més d’una combinació simple de escalat, gir i translació, l’operació dugui implícita una transformació de cisallament. Perquè és clar que si inserim el bloc girat i convertim la inserció en un bloc que al seu torn tornem a inserir, ara però amb escalat no uniforme, el transformat del quadrat de referència primitiu serà un paral·lelogram, però el problema és: dibuixat un marc romboïdal concret, ¿quin gir caldrà donar a la primera inserció, i quin gir i factors d’escala caldrà aplicar a la segona perquè el quadrat de referència s’adapti al marc? El problema es complica si, a més, volem aprofitar el resultat de la primera inserció per a d’altres paral·lelograms, organitzant un sistema no redundant de insercions intermèdies. Doncs bé: INS2D i INS3D donen satisfacció a aquestes qüestions (la segona ja no contempla l'encaix en un paral·lelogram, sinó en un paral·lelepípede) i són aplicables a blocs proveïts d’atributs, no només de tipus convencional (els continguts en el pla de base del bloc, únics de funcionament garantit amb l’ordre INSERT), sinó també dels situats i orientats lliurement.

XML-based information management environment for PE technologies

Printed electronics is an emerging concept in electronics manufacturing and it is in very early development stage. The technology is not stable, design kits are not developed, and flows and Computer Aided Design (CAD) tools are not fixed yet. The European project TDK4PE addresses all this issues and this PFC has been realized on this context. The goal is to develop an XML-based information system for the collection and management of information from the technology and cell libraries developed in TDK4PE. This system will ease the treatment of that information for a later generation of specific Design Kits (DK) and the corresponding documentation. This work proposes a web application to generate technology files and design kits in a formatted way; it also proposes a structure for them and a database implementation for storing the needed information. The application will allow its users to redefine the structure of those files, as well as export and import XML files, between other formats.

Aspects on Process Engineering in the Finnish Pulp and Paper Industry : Thesis for the Degree of Licentiate in Science of Technology

Process development will be largely driven by the main equipment suppliers. The reason for this development is their ambition to supply complete plants or process systems instead of single pieces of equipment. The pulp and paper companies' interest lies in product development, as their main goal is to create winning brands and effective brand management. Design engineering companies will find their niche in detail engineering based on approved process solutions. Their development work will focus on increasing the efficiency of engineering work. Process design is a content-producing profession, which requires certain special characteristics: creativity, carefulness, the ability to work as a member of a design team according to time schedules and fluency in oral as well as written presentation. In the future, process engineers will increasingly need knowledge of chemistry as well as information and automation technology. Process engineering tools are developing rapidly. At the moment, these tools are good enough for static sizing and balancing, but dynamic simulation tools are not yet good enough for the complicated chemical reactions of pulp and paper chemistry. Dynamic simulation and virtual mill models are used as tools for training the operators. Computational fluid dynamics will certainlygain ground in process design.

Promoting Metacognitive Skills in a CSCL environment: implications for instructional and technology design

This paper aims to better understand the development of students’ learning processes when participating actively in a specific Computer Supported Collaborative Learning system called KnowCat. To this end, a longitudinal case study was designed, in which eighteen university students took part in a 12-month (two semesters) learning project. During this time period, the students followed an instructional process, using some elements of KnowCat (KnowCat key features) design to support and improve their interaction processes, especially peer learning processes. Our research involved both supervising the students’ collaborative learning processes throughout the learning project and focusing our analysis on the qualitative evolution of the students’ interaction processes and on the development of metacognitive learning processes. The results of the current research reveal that the instructional application of the CSCL-KnowCat system may favour and improve the development of the students’ metacognitive learning processes. Additionally, the implications of the design of computer supported collaborative learning networks and pedagogical issues are discussed in this paper.

Cam-tekniikan opetusohjelma

Tässä työssä keskitytään rakentamaan opetusohjelma, jonka avulla pyritään kehittämään tietokoneavusteisten valmistusjärjestelmien käyttöä puutuotteiden valmistuksessa. Tavoitteena on cam-teknologian opetustyön ja oppimistapahtuman selkeyttäminen sekä järjestelmän opetuksessa tarvittavan koulutusaineiston luominen. Suunnittelussa pyritään vastaamaan puutuoteteollisuuden tämän hetken tarpeisiin, jotta koulutettavat pystyisivät toimimaan nykyaikaisten cam-järjestelmien parissa. Opetusohjelma sisältää opetuskokonaisuuksia cam-järjestelmän rakenteesta, sen toteuttamisesta ja käytöstä. Lisäksi työssä sovelletaan toteutettua opetusohjelmaa erilaisten kohderyhmien opetussuunnitelmissa ja tutkitaan verkkopohjaisen oppimisympäristön luonnetta ja sen mahdollista käyttöä cam-tekniikan opetuksessa.

Monikappalesysteemin esikäsittelijä kaupallisessa ympäristössä

Työn tavoitteena oli tehdä monikappalesysteemin esikäsittelijä, joka toimii CAD-ohjelmiston yhteydessä. CAD-ohjelmistoksi valittiin SolidWorks-ohjelmisto. Esikäsittelijästä tehtiin yhteensopiva monikappaledynamiikan simulointi ohjelmiston kanssa, joka on kehitetty Lappeenrannan teknillisessä yliopistossa. Aikaansaadun esikäsittelijän avulla pystytään tuottamaan monikappaledynamiikan simuloinnissa tarvittavat lähtötiedot. Lähtötiedot esikäsittelijä laskee käyttäjän tekemästä kokoonpanokuvasta ja käyttäjän antamista tiedoista. Esikäsittelijän toiminta verifioitiin kaupallisin simulointiohjelmisto ADAMS:n avulla. Esikäsittelijän todettiin toimivan luotettavasti ja täyttävän sille asetetut vaatimukset. Lisäksi esikäsittelijän todettiin nopeuttavan huomattavasti simulointimallien tekoa.

Protein pocket and ligand shape comparison and its application in virtual screening.

Understanding molecular recognition is one major requirement for drug discovery and design. Physicochemical and shape complementarity between two binding partners is the driving force during complex formation. In this study, the impact of shape within this process is analyzed. Protein binding pockets and co-crystallized ligands are represented by normalized principal moments of inertia ratios (NPRs). The corresponding descriptor space is triangular, with its corners occupied by spherical, discoid, and elongated shapes. An analysis of a selected set of sc-PDB complexes suggests that pockets and bound ligands avoid spherical shapes, which are, however, prevalent in small unoccupied pockets. Furthermore, a direct shape comparison confirms previous studies that on average only one third of a pocket is filled by its bound ligand, supplemented by a 50 % subpocket coverage. In this study, we found that shape complementary is expressed by low pairwise shape distances in NPR space, short distances between the centers-of-mass, and small deviations in the angle between the first principal ellipsoid axes. Furthermore, it is assessed how different binding pocket parameters are related to bioactivity and binding efficiency of the co-crystallized ligand. In addition, the performance of different shape and size parameters of pockets and ligands is evaluated in a virtual screening scenario performed on four representative targets.

Engineering Geology for Society and Territory: volume 2: landslide processes

This book is one out of 8 IAEG XII Congress volumes, and deals with Landslide processes, including: field data and monitoring techniques, prediction and forecasting of landslide occurrence, regional landslide inventories and dating studies, modeling of slope instabilities and secondary hazards (e.g. impulse waves and landslide-induced tsunamis, landslide dam failures and breaching), hazard and risk assessment, earthquake and rainfall induced landslides, instabilities of volcanic edifices, remedial works and mitigation measures, development of innovative stabilization techniques and applicability to specific engineering geological conditions, use of geophysical techniques for landslide characterization and investigation of triggering mechanisms. Focuses is given to innovative techniques, well documented case studies in different environments, critical components of engineering geological and geotechnical investigations, hydrological and hydrogeological investigations, remote sensing and geophysical techniques, modeling of triggering, collapse, runout and landslide reactivation, geotechnical design and construction procedures in landslide zones, interaction of landslides with structures and infrastructures and possibility of domino effects. The Engineering Geology for Society and Territory volumes of the IAEG XII Congress held in Torino from September 15-19, 2014, analyze the dynamic role of engineering geology in our changing world and build on the four main themes of the congress: environment, processes, issues, and approaches.