An assessment of gene prediction accuracy in large DNA sequences

One of the first useful products from the human genome will be a set of predicted genes. Besides its intrinsic scientific interest, the accuracy and completeness of this data set is of considerable importance for human health and medicine. Though progress has been made on computational gene identification in terms of both methods and accuracy evaluation measures, most of the sequence sets in which the programs are tested are short genomic sequences, and there is concern that these accuracy measures may not extrapolate well to larger, more challenging data sets. Given the absence of experimentally verified large genomic data sets, we constructed a semiartificial test set comprising a number of short single-gene genomic sequences with randomly generated intergenic regions. This test set, which should still present an easier problem than real human genomic sequence, mimics the approximately 200kb long BACs being sequenced. In our experiments with these longer genomic sequences, the accuracy of GENSCAN, one of the most accurate ab initio gene prediction programs, dropped significantly, although its sensitivity remained high. Conversely, the accuracy of similarity-based programs, such as GENEWISE, PROCRUSTES, and BLASTX was not affected significantly by the presence of random intergenic sequence, but depended on the strength of the similarity to the protein homolog. As expected, the accuracy dropped if the models were built using more distant homologs, and we were able to quantitatively estimate this decline. However, the specificities of these techniques are still rather good even when the similarity is weak, which is a desirable characteristic for driving expensive follow-up experiments. Our experiments suggest that though gene prediction will improve with every new protein that is discovered and through improvements in the current set of tools, we still have a long way to go before we can decipher the precise exonic structure of every gene in the human genome using purely computational methodology.

Intracellular nanomanipulation by a photonic-force microscope with real-time acquisition of a 3D stiffness matrix.

A traditional photonic-force microscope (PFM) results in huge sets of data, which requires tedious numerical analysis. In this paper, we propose instead an analog signal processor to attain real-time capabilities while retaining the richness of the traditional PFM data. Our system is devoted to intracellular measurements and is fully interactive through the use of a haptic joystick. Using our specialized analog hardware along with a dedicated algorithm, we can extract the full 3D stiffness matrix of the optical trap in real time, including the off-diagonal cross-terms. Our system is also capable of simultaneously recording data for subsequent offline analysis. This allows us to check that a good correlation exists between the classical analysis of stiffness and our real-time measurements. We monitor the PFM beads using an optical microscope. The force-feedback mechanism of the haptic joystick helps us in interactively guiding the bead inside living cells and collecting information from its (possibly anisotropic) environment. The instantaneous stiffness measurements are also displayed in real time on a graphical user interface. The whole system has been built and is operational; here we present early results that confirm the consistency of the real-time measurements with offline computations.

Right coronary artery flow velocity and volume assessment with spiral K-space sampled breathhold velocity-encoded MRI at 3 tesla: accuracy and reproducibility.

PURPOSE: To evaluate accuracy and reproducibility of flow velocity and volume measurements in a phantom and in human coronary arteries using breathhold velocity-encoded (VE) MRI with spiral k-space sampling at 3 Tesla. MATERIALS AND METHODS: Flow velocity assessment was performed using VE MRI with spiral k-space sampling. Accuracy of VE MRI was tested in vitro at five constant flow rates. Reproducibility was investigated in 19 healthy subjects (mean age 25.4 +/- 1.2 years, 11 men) by repeated acquisition in the right coronary artery (RCA). RESULTS: MRI-measured flow rates correlated strongly with volumetric collection (Pearson correlation r = 0.99; P < 0.01). Due to limited sample resolution, VE MRI overestimated the flow rate by 47% on average when nonconstricted region-of-interest segmentation was used. Using constricted region-of-interest segmentation with lumen size equal to ground-truth luminal size, less than 13% error in flow rate was found. In vivo RCA flow velocity assessment was successful in 82% of the applied studies. High interscan, intra- and inter-observer agreement was found for almost all indices describing coronary flow velocity. Reproducibility for repeated acquisitions varied by less than 16% for peak velocity values and by less than 24% for flow volumes. CONCLUSION: 3T breathhold VE MRI with spiral k-space sampling enables accurate and reproducible assessment of RCA flow velocity.

Patient-specific computational hemodynamics of intracranial aneurysms from 3D rotational angiography and CT angiography: an in vivo reproducibility study

Patient-specific simulations of the hemodynamics in intracranial aneurysms can be constructed by using image-based vascular models and CFD techniques. This work evaluates the impact of the choice of imaging technique on these simulations

Automated Segmentation of Cerebral Vasculature with Aneurysms in 3DRA and TOF-MRA using Geodesic Active Regions: an Evaluation Study

Purpose: To evaluate the suitability of an improved version of an automatic segmentation method based on geodesic active regions (GAR) for segmenting cerebral vasculature with aneurysms from 3D X-ray reconstruc-tion angiography (3DRA) and time of °ight magnetic resonance angiography (TOF-MRA) images available in the clinical routine.Methods: Three aspects of the GAR method have been improved: execution time, robustness to variability in imaging protocols and robustness to variability in image spatial resolutions. The improved GAR was retrospectively evaluated on images from patients containing intracranial aneurysms in the area of the Circle of Willis and imaged with two modalities: 3DRA and TOF-MRA. Images were obtained from two clinical centers, each using di®erent imaging equipment. Evaluation included qualitative and quantitative analyses ofthe segmentation results on 20 images from 10 patients. The gold standard was built from 660 cross-sections (33 per image) of vessels and aneurysms, manually measured by interventional neuroradiologists. GAR has also been compared to an interactive segmentation method: iso-intensity surface extraction (ISE). In addition, since patients had been imaged with the two modalities, we performed an inter-modality agreement analysis with respect to both the manual measurements and each of the two segmentation methods. Results: Both GAR and ISE di®ered from the gold standard within acceptable limits compared to the imaging resolution. GAR (ISE, respectively) had an average accuracy of 0.20 (0.24) mm for 3DRA and 0.27 (0.30) mm for TOF-MRA, and had a repeatability of 0.05 (0.20) mm. Compared to ISE, GAR had a lower qualitative error in the vessel region and a lower quantitative error in the aneurysm region. The repeatabilityof GAR was superior to manual measurements and ISE. The inter-modality agreement was similar between GAR and the manual measurements. Conclusions: The improved GAR method outperformed ISE qualitatively as well as quantitatively and is suitable for segmenting 3DRA and TOF-MRA images from clinical routine.

Temporal diffeomorphic free-form deformation: application to motion and strain estimation from 3D echocardiography

This paper presents a new registration algorithm, called Temporal Di eomorphic Free Form Deformation (TDFFD), and its application to motion and strain quanti cation from a sequence of 3D ultrasound (US) images. The originality of our approach resides in enforcing time consistency by representing the 4D velocity eld as the sum of continuous spatiotemporal B-Spline kernels. The spatiotemporal displacement eld is then recovered through forward Eulerian integration of the non-stationary velocity eld. The strain tensor iscomputed locally using the spatial derivatives of the reconstructed displacement eld. The energy functional considered in this paper weighs two terms: the image similarity and a regularization term. The image similarity metric is the sum of squared di erences between the intensities of each frame and a reference one. Any frame in the sequence can be chosen as reference. The regularization term is based on theincompressibility of myocardial tissue. TDFFD was compared to pairwise 3D FFD and 3D+t FFD, bothon displacement and velocity elds, on a set of synthetic 3D US images with di erent noise levels. TDFFDshowed increased robustness to noise compared to these two state-of-the-art algorithms. TDFFD also proved to be more resistant to a reduced temporal resolution when decimating this synthetic sequence. Finally, this synthetic dataset was used to determine optimal settings of the TDFFD algorithm. Subsequently, TDFFDwas applied to a database of cardiac 3D US images of the left ventricle acquired from 9 healthy volunteers and 13 patients treated by Cardiac Resynchronization Therapy (CRT). On healthy cases, uniform strain patterns were observed over all myocardial segments, as physiologically expected. On all CRT patients, theimprovement in synchrony of regional longitudinal strain correlated with CRT clinical outcome as quanti ed by the reduction of end-systolic left ventricular volume at follow-up (6 and 12 months), showing the potential of the proposed algorithm for the assessment of CRT.

Deployment of self-expandable stents in aneurysmatic cerebral vessels: comparison of different computational approaches for interventional planning

In the last few years, there has been a growing focus on faster computational methods to support clinicians in planning stenting procedures. This study investigates the possibility of introducing computational approximations in modelling stent deployment in aneurysmatic cerebral vessels to achieve simulations compatible with the constraints of real clinical workflows. The release of a self-expandable stent in a simplified aneurysmatic vessel was modelled in four different initial positions. Six progressively simplified modelling approaches (based on Finite Element method and Fast Virtual Stenting – FVS) have been used. Comparing accuracy of the results, the final configuration of the stent is more affected by neglecting mechanical properties of materials (FVS) than by adopting 1D instead of 3D stent models. Nevertheless, the differencesshowed are acceptable compared to those achieved by considering different stent initial positions. Regarding computationalcosts, simulations involving 1D stent features are the only ones feasible in clinical context.

Magnetization transfer-based 3D visualization of foot peripheral nerves.

PURPOSE: To investigate magnetization transfer (MT) effects as a new source of contrast for imaging and tracking of peripheral foot nerves. MATERIALS AND METHODS: Two sets of 3D spoiled gradient-echo images acquired with and without a saturation pulse were used to generate MT ratio (MTR) maps of 260 μm in-plane resolution for eight volunteers at 3T. Scan parameters were adjusted to minimize signal loss due to T2 dephasing, and a dedicated coil was used to improve the inherently low signal-to-noise ratio of small voxels. Resulting MTR values in foot nerves were compared with those in surrounding muscle tissue. RESULTS: Average MTR values for muscle (45.5 ± 1.4%) and nerve (21.4 ± 3.1%) were significantly different (P < 0.0001). In general, the difference in MTR values was sufficiently large to allow for intensity-based segmentation and tracking of foot nerves in individual subjects. This procedure was termed MT-based 3D visualization. CONCLUSION: The MTR serves as a new source of contrast for imaging of peripheral foot nerves and provides a means for high spatial resolution tracking of these structures. The proposed methodology is directly applicable on standard clinical MR scanners and could be applied to systemic pathologies, such as diabetes.

3D-partikkelit aloittelijoille : tarkastelussa 3D-Kalevala-projekti

Opinnäytteeni teososana on 3D-Kalevala projektinimellä tunnetun animaation partikkeliefektit. Tarkastelen tarkemmin elokuvan Lumi-, Kylä-, Paja- ja Luola-kohtauksia. 3D-Kalevala on tietokoneella tehty animaatio, joka kertoo Suomen kansalliseepoksen Kalevalan päähenkilöstä Väinämöisestä. Elokuvassa vanha Väinämöinen muistelee nuoruutensa tapahtumia. 3D-Kalevala-projekti käynnistettiin vuonna 2003, mutta sen alkuperäiset tekijät eivät saaneet sitä valmiiksi, ja projektin teko keskeytettiin vuonna 2005. Vuoden 2006 keväällä projektiin perustettiin uusi kahden verkkoviestinnän opiskelijan projektiryhmä, jonka tehtävänä oli saada elokuva valmiiksi vuoden 2007 kevääseen mennessä. Kun aloitimme projektin tekemisen, olin kolmiulotteisessa mallinnuksessa aloittelija. Tästä johtuen opinnäytteen kirjallinen osa on opas aloittelijoille partikkelien maailmaan. Selvitän raportissani miten elokuvan partikkeliefektit rakennettiin, mitä niiden tekeminen minulta vaati ja miten ne loppujen lopuksi mielestäni onnistuivat. Elokuvan efektit tehtiin 3D Studio Max-ohjelman versiolla 6.0, ja tämän takia kirjoitankin efektien rakentamisesta kyseisen ohjelman keinoin. Projektin suuruuden vuoksi molemmat tekijät pääsivät tekemään monenlaisia töitä, mutta päävastuualueet olivat selvät. Minun osani oli tehdä elokuvaan efektejä. Partikkeliefektit ovat proseduraalisia efektejä, joiden avulla on mahdollista tehdä aidon näköisiä luonnonilmiöitä, kuten tulta, savua, kipinöitä ja veden roiskeita. Koska partikkeliefektit mallintavat reaalimaailman ilmiöitä, on tekijän hyvä olla kiinnostunut selvittämään ilmiöiden käyttäytymistä luonnossa. Raportoin myös projektin aikana huomaamistani hyvistä tavoista opiskella itsenäisesti partikkelien rakentamiseen käytettyjä tekniikoita. On hyvä lukea 3D Studio Maxin tasokasta käyttöohjesovellusta, tutustua Internetissä löytyviin 3D-aiheisiin foorumeihin, käydä aiheesta tutoriaaleja läpi sekä tutustua ohjelman ominaisuuksiin kokeilemalla ja tutkimalla itsenäisesti. Elokuvan efektit onnistuivat mielestäni kiitettävästi ottaen huomioon lähtötasoni. Löysin tapoja kehittää itseäni ja helppoja keinoja toteuttaa realistista jälkeä efektien rakentamisessa. Toivon, että raportistani olisi jollekin 3D-partikkeliefekteistä kiinnostuneelle hyötyä.

Keskeytyneen uusmediatuotannon jatkaminen : kohteena 3D-Kalevala

Opinnäytetyöni aiheena on keskeytyneen uusmediatuotannon jatkaminen. Monimuototyön työosana toteutettiin 7-minuuttinen 3D animaatio, joka kertoo Suomen kansalliseepoksen Kalevalan taruhahmosta Väinämöisestä, muistelemassa menneitä. Projekti käynnistettiin alun perin vuonna 2003, mutta resurssien vähetessä se keskeytyi vuoden 2005 loppupuolella. Keväällä 2006 projekti käynnistettiin uuden projektiryhmän voimin, jossa olin itse mukana vastaten muun muassa tuotannonohjauksesta ja hahmoanimoinneista. Uusi projektiryhmä oli henkilöstöresursseiltaan pieni, joten vastuualueet olivat monipuolisia. Keskeytyneen projektin jatkamisen ja haltuunoton haasteellisuus sai minut kiinnostumaan tutkia aihetta tarkemmin. Tuotannonohjaajana vastasin hyvin pitkälle tuotannon uudesta käynnistämisestä ja projektin saattamisesta vihdoin loppuun. Keskeytyneen projektin haltuunotto oli tilanteena kaikille uusi, mikä heijastui vaikeuksina uudelleen käynnistettyyn tuotantoon. Raportin tarkoituksena ei ole olla projektinhallinnallinen käsikirja, sillä käsittelen vain tämän projektin jatkolle oleellisina pidettyjä asioita. Projekti toivottavasti kuitenkin antaa kuvan huolellisen projektinhallinnan ja onnistuneen tuotannonohjauksen tärkeydestä. Jokainen keskeytynyt projekti ei ole aina välttämättä elvytettävissä - ainakaan alkuperäisessä muodossaan. Projektin jatkamista tulisi katsoa aina tapauskohtaisesti. Keskeytymiseen on useimmiten syynsä, joten ongelmien selvittäminen ja niihin puuttuminen on tärkeää ennen jatkopäätöksen tekemistä. Myös projektityöskentelytavat kehittyvät ja pohdin työssäni uusien projektinhallintatapojen, kuten wikien käyttöä projektinhallinnan työkaluna ja projektiyhteisön välistä viestintää edistävänä työkaluna.

Dual-wavelength digital holographic microscopy with sub-nanometer axial accuracy

We present dual-wavelength Digital Holographic Microscopy (DHM) measurements on a certified 8.9 nm high Chromium thin step sample and demonstrate sub-nanometer axial accuracy. We introduce a modified DHM Reference Calibrated Hologram (RCH) reconstruction algorithm taking into account amplitude contributions. By combining this with a temporal averaging procedure and a specific dual-wavelength DHM arrangement, it is shown that specimen topography can be measured with an accuracy, defined as the axial standard deviation, reduced to at least 0.9 nm. Indeed, it is reported that averaging each of the two wavefronts recorded with real-time dual-wavelength DHM can provide up to 30% spatial noise reduction for the given configuration, thanks to their non-correlated nature. ©2008 COPYRIGHT SPIE

Nursing diagnosis sedentary lifestyle in individuals with hypertension: an analysis of accuracy

Objective Assessing the accuracy of the defining characteristics (DC) of the nursing diagnosis Sedentary Lifestyle (SL) in people with hypertension. Method A cross-sectional study carried out in a referral center in the outpatient care of people with hypertension and diabetes, with a sample of 285 individuals. The form used in the study was designed from operational definitions constructed for each DC of the diagnosis. Four nurses with training to carry out diagnostic inferences did the clinical assessment for the presence of SL. Results The prevalence of SL was 55.8%. Regarding measures of accuracy, the main DC for SL was chooses a daily routine lacking physical exercise, with sensitivity of 100% and specificity of 84.13%. Two DC stood out in the logistic regression, namely: reports preference for activities low in physical activity and poor performance in instrumental activities of daily living (IADL). Conclusion The results allowed identifying the best clinical indicators for SL in hypertensive adults.

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency.

Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.

High-resolution 3D whole-heart coronary MRA: a study on the combination of data acquisition in multiple breath-holds and 1D residual respiratory motion compensation.

OBJECT: To study a scan protocol for coronary magnetic resonance angiography based on multiple breath-holds featuring 1D motion compensation and to compare the resulting image quality to a navigator-gated free-breathing acquisition. Image reconstruction was performed using L1 regularized iterative SENSE. MATERIALS AND METHODS: The effects of respiratory motion on the Cartesian sampling scheme were minimized by performing data acquisition in multiple breath-holds. During the scan, repetitive readouts through a k-space center were used to detect and correct the respiratory displacement of the heart by exploiting the self-navigation principle in image reconstruction. In vivo experiments were performed in nine healthy volunteers and the resulting image quality was compared to a navigator-gated reference in terms of vessel length and sharpness. RESULTS: Acquisition in breath-hold is an effective method to reduce the scan time by more than 30 % compared to the navigator-gated reference. Although an equivalent mean image quality with respect to the reference was achieved with the proposed method, the 1D motion compensation did not work equally well in all cases. CONCLUSION: In general, the image quality scaled with the robustness of the motion compensation. Nevertheless, the featured setup provides a positive basis for future extension with more advanced motion compensation methods.