Single breath-hold 3D measurement of left atrial volume using compressed sensing cardiovascular magnetic resonance and a non-model-based reconstruction approach.

BACKGROUND: Left atrial (LA) dilatation is associated with a large variety of cardiac diseases. Current cardiovascular magnetic resonance (CMR) strategies to measure LA volumes are based on multi-breath-hold multi-slice acquisitions, which are time-consuming and susceptible to misregistration. AIM: To develop a time-efficient single breath-hold 3D CMR acquisition and reconstruction method to precisely measure LA volumes and function. METHODS: A highly accelerated compressed-sensing multi-slice cine sequence (CS-cineCMR) was combined with a non-model-based 3D reconstruction method to measure LA volumes with high temporal and spatial resolution during a single breath-hold. This approach was validated in LA phantoms of different shapes and applied in 3 patients. In addition, the influence of slice orientations on accuracy was evaluated in the LA phantoms for the new approach in comparison with a conventional model-based biplane area-length reconstruction. As a reference in patients, a self-navigated high-resolution whole-heart 3D dataset (3D-HR-CMR) was acquired during mid-diastole to yield accurate LA volumes. RESULTS: Phantom studies. LA volumes were accurately measured by CS-cineCMR with a mean difference of -4.73 ± 1.75 ml (-8.67 ± 3.54%, r2 = 0.94). For the new method the calculated volumes were not significantly different when different orientations of the CS-cineCMR slices were applied to cover the LA phantoms. Long-axis "aligned" vs "not aligned" with the phantom long-axis yielded similar differences vs the reference volume (-4.87 ± 1.73 ml vs. -4.45 ± 1.97 ml, p = 0.67) and short-axis "perpendicular" vs. "not-perpendicular" with the LA long-axis (-4.72 ± 1.66 ml vs. -4.75 ± 2.13 ml; p = 0.98). The conventional bi-plane area-length method was susceptible for slice orientations (p = 0.0085 for the interaction of "slice orientation" and "reconstruction technique", 2-way ANOVA for repeated measures). To use the 3D-HR-CMR as the reference for LA volumes in patients, it was validated in the LA phantoms (mean difference: -1.37 ± 1.35 ml, -2.38 ± 2.44%, r2 = 0.97). Patient study: The CS-cineCMR LA volumes of the mid-diastolic frame matched closely with the reference LA volume (measured by 3D-HR-CMR) with a difference of -2.66 ± 6.5 ml (3.0% underestimation; true LA volumes: 63 ml, 62 ml, and 395 ml). Finally, a high intra- and inter-observer agreement for maximal and minimal LA volume measurement is also shown. CONCLUSIONS: The proposed method combines a highly accelerated single-breathhold compressed-sensing multi-slice CMR technique with a non-model-based 3D reconstruction to accurately and reproducibly measure LA volumes and function.

3D-suunnittelujärjestelmän ja tuotetiedonhallintajärjestelmän integrointi

3D-suunnittelujärjestelmät ovat tärkeitä työkaluja tuotetiedon luomista ja muokkaamista varten, joten niiden tehokas toiminta yhdessä tuotetiedonhallintajärjestelmien kanssa on erittäin tärkeää. 3D-suunnittelujärjestelmien kehityksen seurauksena 3D-malleihin voidaan sisällyttää entistä enemmän tuotetietoa, jolloin tehokas tiedon tallentaminen ja sen hallinta kasvattaa merkitystään. 3D-malleihin sisältyvää tietoa, kuten esimerkiksi kappaleen painoa tai geometriaa, halutaan myös tarkastella ilman tiettyä 3D-järjestelmää. Tuotetiedon hallinta on ollut jo pitkään tärkeä osa tuotteen suunnitteluprosessia. Tuotetiedon hallintaan sisältyy tiedon luomista, keräämistä ja muokkaamista koko tuotteen eliniän ajan. Näitä tietoja voivat olla esimerkiksi piirustukset, 3D-mallit, mittauspöytäkirjat, kokouspöytäkirjat, mallistoluettelot, lujuuslaskelmat, huoltoraportit jne. Tuotetiedonhallintajärjestelmä pitää huolta kaikesta tästä tiedosta ja sen kautta tuotteisiin liittyvää tietoa voidaan myös muokata ja jakaa tehokkaasti. Tässä diplomityössä tutkittiin näiden kahden järjestelmän integraation toteutusta erilaisilla menetelmillä. Työn tarkoituksena oli valita Valtra Oy:n tarkoituksiin parhaiten sopiva menetelmä tuotetiedon siirtämiseksi järjestelmien välillä tehokkaasti. Työn tuloksena annetaan suositus käytettävistä menetelmistä ja työkaluista.

Towards a digital body: the virtual arm illusion

The integration of the human brain with computers is an interesting new area of applied neuroscience, where one application is replacement of a person"s real body by a virtual representation. Here we demonstrate that a virtual limb can be made to feel part of your body if appropriate multisensory correlations are provided. We report an illusion that is invoked through tactile stimulation on a person"s hidden real right hand with synchronous virtual visual stimulation on an aligned 3D stereo virtual arm projecting horizontally out of their shoulder. An experiment with 21 male participants showed displacement of ownership towards the virtual hand, as illustrated by questionnaire responses and proprioceptive drift. A control experiment with asynchronous tapping was carried out with a different set of 20 male participants who did not experience the illusion. After 5 min of stimulation the virtual arm rotated. Evidence suggests that the extent of the illusion was also correlated with the degree of muscle activity onset in the right arm as measured by EMG during this period that the arm was rotating, for the synchronous but not the asynchronous condition. A completely virtual object can therefore be experienced as part of one"s self, which opens up the possibility that an entire virtual body could be felt as one"s own in future virtual reality applications or online games, and be an invaluable tool for the understanding of the brain mechanisms underlying body ownership.

Generació d’un entorn virtual de treball per un robot Stäubli TX60

L’objectiu del treball és emular virtualment l’entorn de treball del robot Stäubli Tx60 quehi ha al laboratori de robòtica de la UdG (dins les possibilitats que ofereix el software adquirit).Aquest laboratori intenta reproduir un entorn industrial de treball en el qual es realitzal’assemblatge d’un conjunt de manera cent per cent automatitzada.En una primera fase, s’ha dissenyat en tres dimensions tot l’entorn de treball que hi hadisponible al laboratori a través del software CAD SolidWorks. Cada un dels conjuntsque conformen l’estació de treball s’ha dissenyat de manera independent.Posteriorment s’introdueixen tots els elements dissenyats dins el software StäubliRobotics Suite 2013. Amb tot l’anterior, cal remarcar que l’objectiu principal del treball consta de duesetapes. Inicialment es dissenya el model 3D de l’entorn de treball a través del software SolidWorks i s’introdueix dins el software Stäubli Robotics Suite 2013. Enuna segona etapa, es realitza un manual d’ús del nou software de robòtica

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.

Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

Student Journalism 2.0 : Testing Models for Participatory Learning in the Digital Age

Many educators and educational institutions have yet to integrate web-based practices into their classrooms and curricula. As a result, it can be difficult to prototype and evaluate approaches to transforming classrooms from static endpoints to dynamic, content-creating nodes in the online information ecosystem. But many scholastic journalism programs have already embraced the capabilities of the Internet for virtual collaboration, dissemination, and reader participation. Because of this, scholastic journalism can act as a test-bed for integrating web-based sharing and collaboration practices into classrooms. Student Journalism 2.0 was a research project to integrate open copyright licenses into two scholastic journalism programs, to document outcomes, and to identify recommendations and remaining challenges for similar integrations. Video and audio recordings of two participating high school journalism programs informed the research. In describing the steps of our integration process, we note some important legal, technical, and social challenges. Legal worries such as uncertainty over copyright ownership could lead districts and administrators to disallow open licensing of student work. Publication platforms among journalism classrooms are far from standardized, making any integration of new technologies and practices difficult to achieve at scale. And teachers and students face challenges re-conceptualizing the role their class work can play online.

3D Surface Modeling From Point Clouds

The goal of this thesis is to implement software for creating 3D models from point clouds. Point clouds are acquired with stereo cameras, monocular systems or laser scanners. The created 3D models are triangular models or NURBS (Non-Uniform Rational B-Splines) models. Triangular models are constructed from selected areas from the point clouds and resulted triangular models are translated into a set of quads. The quads are further translated into an estimated grid structure and used for NURBS surface approximation. Finally, we have a set of NURBS surfaces which represent the whole model. The problem wasn’t so easy to solve. The selected triangular surface reconstruction algorithm did not deal well with noise in point clouds. To handle this problem, a clustering method is introduced for simplificating the model and removing noise. As we had better results with the smaller point clouds produced by clustering, we used points in clusters to better estimate the grids for NURBS models. The overall results were good when the point cloud did not have much noise. The point clouds with small amount of error had good results as the triangular model was solid. NURBS surface reconstruction performed well on solid models.

Visualitzador de molècules d'ADN per laboratori virtual

Com a continuació del treball de final de carrera “Desenvolupament d’un laboratori virtual per a les pràctiques de Biologia Molecular” de Jordi Romero, s’ha realitzat una eina complementaria per a la visualització de molècules integrada en el propi laboratori virtual. Es tracta d’una eina per a la visualització gràfica de gens, ORF, marques i seqüències de restricció de molècules reals o fictícies. El fet de poder treballar amb molècules fictícies és la gran avantatge respecte a les solucions com GENBANK que només permet treballar amb molècules pròpies. Treballar amb molècules fictícies fa que sigui una solució ideal per a l’ensenyament, ja que dóna la possibilitat als professors de realitzar exercicis o demostracions amb molècules reals o dissenyades expressament per a l’exercici a demostrar. A més, permet mostrar de forma visual les diferents parts simultàniament o per separat, de manera que ofereix una primera aproximació interpretació dels resultats. Per altra banda, permet marcar gens, crear marques, localitzar seqüències de restricció i generar els ORF de la molècula que nosaltres creem o modificar una ja existent. Per l’implementació, s’ha continuat amb l’idea de separar la part de codi i la part de disseny en les aplicacions Flash. Per fer-ho, s’ha utilitzat la plataforma de codi lliure Ariware ARPv2.02 que proposa un marc de desenvolupament d’aplicacions Flash orientades a objectes amb el codi (classes ActionScript 2.0) separats del movieclip. Per al processament de dades s’ha fet servir Perl per ser altament utilitzat en Bioinformàtica i per velocitat de càlcul. Les dades generades es guarden en una Base de Dades en MYSQL (de lliure distribució), de la que s’extreuen les dades per generar fitxers XML, fent servir tant PHP com la plataforma AMFPHP com a enllaç entre Flash i la resta de parts.

Estudos de QSAR 3D para um conjunto de inibidores de butirilcolinesterase humana

Alzheimer's disease (AD) is considered the main cause of cognitive decline in adults. The available therapies for AD treatment seek to maintain the activity of cholinergic system through the inhibition of the enzyme acetylcholinesterase. However, butyrylcholinesterase (BuChE) can be considered an alternative target for AD treatment. Aiming at developing new BuChE inhibitors, robust QSAR 3D models with high predictive power were developed. The best model presents a good fit (r²=0.82, q²=0.76, with two PCs) and high predictive power (r²predict=0.88). Analysis of regression vector shows that steric properties have considerable importance to the inhibition of the BuChE.

QSAR-3D/CoMFA em compostos imídicos com atividade antinociceptiva

Imide compounds have shown biological activity. These compounds can be easily synthesized with good yields. The objective of this paper was the rational planning of imides and sulfonamides with antinociceptive activity using the 3D-QSAR/CoMFA approach. The studies were performed using two data sets. The first set consisted of 39 cyclic imides while the second set consisted of 39 imides and 15 sulfonamides. The 3D- QSAR/CoMFA models have shown that the steric effect is important for the antinociceptive activity of imide and sulphonamide compounds. Ten new compounds with improved potential antinociceptive activity have been proposed by de novo design leapfrog simulations.

CFD Modelling of Direct Contact Condensation in Suppression Pools by Applying Condensation Models of Separated Flow

The condensation rate has to be high in the safety pressure suppression pool systems of Boiling Water Reactors (BWR) in order to fulfill their safety function. The phenomena due to such a high direct contact condensation (DCC) rate turn out to be very challenging to be analysed either with experiments or numerical simulations. In this thesis, the suppression pool experiments carried out in the POOLEX facility of Lappeenranta University of Technology were simulated. Two different condensation modes were modelled by using the 2-phase CFD codes NEPTUNE CFD and TransAT. The DCC models applied were the typical ones to be used for separated flows in channels, and their applicability to the rapidly condensing flow in the condensation pool context had not been tested earlier. A low Reynolds number case was the first to be simulated. The POOLEX experiment STB-31 was operated near the conditions between the ’quasi-steady oscillatory interface condensation’ mode and the ’condensation within the blowdown pipe’ mode. The condensation models of Lakehal et al. and Coste & Lavi´eville predicted the condensation rate quite accurately, while the other tested ones overestimated it. It was possible to get the direct phase change solution to settle near to the measured values, but a very high resolution of calculation grid was needed. Secondly, a high Reynolds number case corresponding to the ’chugging’ mode was simulated. The POOLEX experiment STB-28 was chosen, because various standard and highspeed video samples of bubbles were recorded during it. In order to extract numerical information from the video material, a pattern recognition procedure was programmed. The bubble size distributions and the frequencies of chugging were calculated with this procedure. With the statistical data of the bubble sizes and temporal data of the bubble/jet appearance, it was possible to compare the condensation rates between the experiment and the CFD simulations. In the chugging simulations, a spherically curvilinear calculation grid at the blowdown pipe exit improved the convergence and decreased the required cell count. The compressible flow solver with complete steam-tables was beneficial for the numerical success of the simulations. The Hughes-Duffey model and, to some extent, the Coste & Lavi´eville model produced realistic chugging behavior. The initial level of the steam/water interface was an important factor to determine the initiation of the chugging. If the interface was initialized with a water level high enough inside the blowdown pipe, the vigorous penetration of a water plug into the pool created a turbulent wake which invoked the chugging that was self-sustaining. A 3D simulation with a suitable DCC model produced qualitatively very realistic shapes of the chugging bubbles and jets. The comparative FFT analysis of the bubble size data and the pool bottom pressure data gave useful information to distinguish the eigenmodes of chugging, bubbling, and pool structure oscillations.

A Farewell to Flat Biology. Three-dimensional Cell Culture Models in Cancer Drug Target Identification and Validation

Cells of epithelial origin, e.g. from breast and prostate cancers, effectively differentiate into complex multicellular structures when cultured in three-dimensions (3D) instead of conventional two-dimensional (2D) adherent surfaces. The spectrum of different organotypic morphologies is highly dependent on the culture environment that can be either non-adherent or scaffold-based. When embedded in physiological extracellular matrices (ECMs), such as laminin-rich basement membrane extracts, normal epithelial cells differentiate into acinar spheroids reminiscent of glandular ductal structures. Transformed cancer cells, in contrast, typically fail to undergo acinar morphogenic patterns, forming poorly differentiated or invasive multicellular structures. The 3D cancer spheroids are widely accepted to better recapitulate various tumorigenic processes and drug responses. So far, however, 3D models have been employed predominantly in the Academia, whereas the pharmaceutical industry has yet to adopt a more widely and routine use. This is mainly due to poor characterisation of cell models, lack of standardised workflows and high throughput cell culture platforms, and the availability of proper readout and quantification tools. In this thesis, a complete workflow has been established entailing well-characterised 3D cell culture models for prostate cancer, a standardised 3D cell culture routine based on high-throughput-ready platform, automated image acquisition with concomitant morphometric image analysis, and data visualisation, in order to enable large-scale high-content screens. Our integrated suite of software and statistical analysis tools were optimised and validated using a comprehensive panel of prostate cancer cell lines and 3D models. The tools quantify multiple key cancer-relevant morphological features, ranging from cancer cell invasion through multicellular differentiation to growth, and detect dynamic changes both in morphology and function, such as cell death and apoptosis, in response to experimental perturbations including RNA interference and small molecule inhibitors. Our panel of cell lines included many non-transformed and most currently available classic prostate cancer cell lines, which were characterised for their morphogenetic properties in 3D laminin-rich ECM. The phenotypes and gene expression profiles were evaluated concerning their relevance for pre-clinical drug discovery, disease modelling and basic research. In addition, a spontaneous model for invasive transformation was discovered, displaying a highdegree of epithelial plasticity. This plasticity is mediated by an abundant bioactive serum lipid, lysophosphatidic acid (LPA), and its receptor LPAR1. The invasive transformation was caused by abrupt cytoskeletal rearrangement through impaired G protein alpha 12/13 and RhoA/ROCK, and mediated by upregulated adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A, and Rac/ PAK pathways. The spontaneous invasion model tangibly exemplifies the biological relevance of organotypic cell culture models. Overall, this thesis work underlines the power of novel morphometric screening tools in drug discovery.

Validation of a 3D model for oxygen combustion in a circulating fluidized bed

In this thesis, a model called CFB3D is validated for oxygen combustion in circulating fluidized bed boiler. The first part of the work consists of literature review in which circulating fluidized bed and oxygen combustion technologies are studied. In addition, the modeling of circulating fluidized bed furnaces is discussed and currently available industrial scale three-dimensional furnace models are presented. The main features of CFB3D model are presented along with the theories and equations related to the model parameters used in this work. The second part of this work consists of the actual research and modeling work including measurements, model setup, and modeling results. The objectives of this thesis is to study how well CFB3D model works with oxygen combustion compared to air combustion in circulating fluidized bed boiler and what model parameters need to be adjusted when changing from air to oxygen combustion. The study is performed by modeling two air combustion cases and two oxygen combustion cases with comparable boiler loads. The cases are measured at Ciuden 30 MWth Flexi-Burn demonstration plant in April 2012. The modeled furnace temperatures match with the measurements as well in oxygen combustion cases as in air combustion cases but the modeled gas concentrations differ from the measurements clearly more in oxygen combustion cases. However, the same model parameters are optimal for both air and oxygen combustion cases. When the boiler load is changed, some combustion and heat transfer related model parameters need to be adjusted. To improve the accuracy of modeling results, better flow dynamics model should be developed in the CFB3D model. Additionally, more measurements are needed from the lower furnace to find the best model parameters for each case. The validation work needs to be continued in order to improve the modeling results and model predictability.

Virtual technology and haptic interface solutions for design and control of mobile working machines

Commercially available haptic interfaces are usable for many purposes. However, as generic devices they are not the most suitable for the control of heavy duty mobile working machines like mining machines, container handling equipment and excavators. Alternative mechanical constructions for a haptic controller are presented and analysed. A virtual reality environment (VRE) was built to test the proposed haptic controller mechanisms. Verification of an electric motor emulating a hydraulic pump in the electro-hydraulic system of a mobile working machine is carried out. A real-time simulator using multi-body-dynamics based software with hardware-in-loop (HIL) setup was used for the tests. Recommendations for further development of a haptic controller and emulator electric motor are given.