Structures of human purine nucleoside phosphorylase complexed with inosine and ddI

Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme which plays a key role in the purine salvage pathway, and PNP deficiency in humans leads to an impairment of T-cell function, usually with no apparent effect on B-cell function. PNP is highly specific for 6-oxopurine nucleosides and exhibits negligible activity for 6-aminopurine nucleosides. The catalytic efficiency for inosine is 350,000-fold greater than for adenosine. Adenine nucleosides and nucleotides are deaminated by adenosine deaminase and AMP deaminase to their corresponding inosine derivatives which, in turn, may be further degraded. Here we report the crystal structures of human PNP in complex with inosine and 2',3'-dideoxymosine, refined to 2.8 Angstrom resolution using synchrotron radiation. The present structures provide explanation for ligand binding, refine the purine-binding site, and can be used for future inhibitor design. (C) 2003 Elsevier B.V. All rights reserved.

Crystal structure of human PNP complexed with hypoxanthine and sulfate ion

Purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme, which plays a key role in the purine salvage pathway, and PNP deficiency in humans leads to an impairment of T-cell function, usually with no apparent effects on B-cell function. Human PNP has been submitted to intensive structure-based design of inhibitors, most of them using low-resolution structures of human PNP. Here we report the crystal structure of human PNP in complex with hypoxanthine, refined to 2.6 Angstrom resolution. The intermolecular interaction between ligand and PNP is discussed. (C) 2004 Elsevier B.V. All rights reserved.

Determination of anaerobic threshold in rats using the lactate minimum test

The break point of the curve of blood lactate vs exercise load has been called anaerobic threshold (AT) and is considered to be an important indicator of endurance exercise capacity in human subjects. There are few studies of AT determination in animals. We describe a protocol for AT determination by the lactate minimum test in rats during swimming exercise. The test is based on the premise that during an incremental exercise test, and after a bout of maximal exercise, blood lactate decreases to a minimum and then increases again. This minimum value indicates the intensity of the AT. Adult male (90 days) Wistar rats adapted to swimming for 2 weeks were used. The initial state of lactic acidosis was obtained by making the animals jump into the water and swim while carrying a load equivalent to 50% of body weight for 6 min (30-s exercise interrupted by a 30-s rest). After a 9-min rest, blood was collected and the incremental swimming test was started. The test consisted of swimming while supporting loads of 4.5, 5.0, 5.5, 6.0 and 7.0% of body weight. Each exercise load lasted 5 min and was followed by a 30-s rest during which blood samples were taken. The blood lactate minimum was determined from a zero-gradient tangent to a spline function fitting the blood lactate vs workload curve. AT was estimated to be 4.95 ± 0.10% of body weight while interpolated blood lactate was 7.17 ± 0.16 mmol/l. These results suggest the application of AT determination in animal studies concerning metabolism during exercise.

Comparação das intensidades correspondentes ao lactato mínimo, limiar de lactato e limiar anaeróbio durante o ciclismo em atletas de endurance

O objetivo deste estudo foi comparar a intensidade de exercício no lactato mínimo (LACmin), com a intensidade correspondente ao limiar de lactato (LL) e limiar anaeróbio (LAn). Participaram do estudo, 11 atletas do sexo masculino (idade, 22,5 + 3,17 anos; altura, 172,3 + 8,2 cm; peso, 66,9 + 8,2kg; e gordura corporal, 9,8 + 3,4%). Os indivíduos foram submetidos, em uma bicicleta eletromagnética (Quinton - Corival 400), a dois testes: 1) exercício contínuo de cargas crescentes - carga inicial de 100W, com incrementos de 25W a cada três min. até a exaustão voluntária; e 2) teste de lactato mínimo - inicialmente os indivíduos pedalaram duas vezes 425W (+ 120%max) durante 30 segundos, com um min. de intervalo, com o objetivo de induzir o acúmulo de lactato. Após oito min. de recuperação passiva, os indivíduos iniciaram um teste contínuo de cargas progressivas, idêntico ao descrito anteriormente. O LL e o LAn foram identificados como sendo o menor valor entre a razão - lactato sanguíneo (mM) / intensidade de exercício (W), e a intensidade correspondente a 3,5mM de lactato sanguíneo, respectivamente. O LACmin foi identificado como sendo a intensidade correspondente a menor concentração de lactato durante o teste de cargas progressivas. Não foi observada diferença significante entre a potência do LL (197,7 + 20,7W) e do LACmin (201,6 + 13,0W), sendo ambas significantemente menores do que do LAn (256,7 + 33,3W). Não foram encontradas também diferenças significantes para o (ml.kg-1.min-1) e a FC (bpm) obtidos no LL (43,2 + 5,01; 152,0 + 13,0) e no LACmin (42,1 + 3,9; 159,0 + 10,0), sendo entretanto significantemente menores do que os obtidos para o LAn (52,2 + 8,2; 174,0 + 13,0, respectivamente). Pode-se concluir que o teste de LACmin, nas condições experimentais deste estudo, pode subestimar a intensidade de MSSLAC (estimada indiretamente pelo LAn), o que concordacom outros estudos que determinaram a MSSLAC diretamente. Assim, são necessários mais estudos que analisem o possível componente tempo-dependente (intensidade inicial) que pode existir no protocolo do LACmin.

Controle de qualidade aplicado na modelagem digital de terreno

Pós-graduação em Ciências Cartográficas - FCT

Polynomials to model the growth of young bulls in performance tests

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Superfici di suddivisione: teoria, algoritmi ed applicazioni

Le superfici di suddivisione sono un ottimo ed importante strumento utilizzato principalmente nell’ambito dell’animazione 3D poichè consentono di definire superfici di forma arbitraria. Questa tecnologia estende il concetto di B-spline e permette di avere un’estrema libertà dei vincoli topologici. Per definire superfici di forma arbitraria esistono anche le Non-Uniform Rational B-Splines (NURBS) ma non lasciano abbastanza libertà per la costruzione di forme libere. Infatti, a differenza delle superfici di suddivisione, hanno bisogno di unire vari pezzi della superficie (trimming). La tecnologia NURBS quindi viene utilizzata prevalentemente negli ambienti CAD mentre nell’ambito della Computer Graphics si è diffuso ormai da più di 30 anni, l’utilizzo delle superfici di suddivisione. Lo scopo di questa tesi è quello di riassumere, quindi, i concetti riguardo questa tecnologia, di analizzare alcuni degli schemi di suddivisione più utilizzati e parlare brevemente di come questi schemi ed algoritmi vengono utilizzati nella realt`a per l’animazione 3D.

ANALYSIS AND VISUALIZATION OF FLOW FIELDS USING INFORMATION-THEORETIC TECHNIQUES AND GRAPH-BASED REPRESENTATIONS

Three-dimensional flow visualization plays an essential role in many areas of science and engineering, such as aero- and hydro-dynamical systems which dominate various physical and natural phenomena. For popular methods such as the streamline visualization to be effective, they should capture the underlying flow features while facilitating user observation and understanding of the flow field in a clear manner. My research mainly focuses on the analysis and visualization of flow fields using various techniques, e.g. information-theoretic techniques and graph-based representations. Since the streamline visualization is a popular technique in flow field visualization, how to select good streamlines to capture flow patterns and how to pick good viewpoints to observe flow fields become critical. We treat streamline selection and viewpoint selection as symmetric problems and solve them simultaneously using the dual information channel [81]. To the best of my knowledge, this is the first attempt in flow visualization to combine these two selection problems in a unified approach. This work selects streamline in a view-independent manner and the selected streamlines will not change for all viewpoints. My another work [56] uses an information-theoretic approach to evaluate the importance of each streamline under various sample viewpoints and presents a solution for view-dependent streamline selection that guarantees coherent streamline update when the view changes gradually. When projecting 3D streamlines to 2D images for viewing, occlusion and clutter become inevitable. To address this challenge, we design FlowGraph [57, 58], a novel compound graph representation that organizes field line clusters and spatiotemporal regions hierarchically for occlusion-free and controllable visual exploration. We enable observation and exploration of the relationships among field line clusters, spatiotemporal regions and their interconnection in the transformed space. Most viewpoint selection methods only consider the external viewpoints outside of the flow field. This will not convey a clear observation when the flow field is clutter on the boundary side. Therefore, we propose a new way to explore flow fields by selecting several internal viewpoints around the flow features inside of the flow field and then generating a B-Spline curve path traversing these viewpoints to provide users with closeup views of the flow field for detailed observation of hidden or occluded internal flow features [54]. This work is also extended to deal with unsteady flow fields. Besides flow field visualization, some other topics relevant to visualization also attract my attention. In iGraph [31], we leverage a distributed system along with a tiled display wall to provide users with high-resolution visual analytics of big image and text collections in real time. Developing pedagogical visualization tools forms my other research focus. Since most cryptography algorithms use sophisticated mathematics, it is difficult for beginners to understand both what the algorithm does and how the algorithm does that. Therefore, we develop a set of visualization tools to provide users with an intuitive way to learn and understand these algorithms.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (function was evaluated using the validated Gastrointestinal Quality of Life Index questionnaire and an institutional questionnaire regarding post-cystectomy outcome. Local recurrences and distal metastases were evaluated using computed tomography and bone scan at the regular follow-up visits. RESULTS There was no significant difference between the two groups in terms of the rate of local (pelvic) recurrence (5/95 [5.3%] in group A; 7/93 [7.5%] in group B; p = 0.53), the rate of distant metastases (21/95 [22.1%] in group A; 23/93 [24.7%] in group B; p = 0.67), cancer-specific survival (p = 0.37), and overall survival (p = 0.59). Group A had significantly better bowel function at 3 (p < 0.001), 6 (p < 0.006), 12 (p <0.006) and 24 months (p = 0.04), and significantly less postoperative abdominal pain and bloating at 3 (p = 0.002) and 6 months (p = 0.01). CONCLUSION Readaptation of the dorsolateral peritoneal layer following PLND and cystectomy has a beneficial long-term impact on bowel function and postoperative pain without compromising oncological radicality. This article is protected by copyright. All rights reserved.

Non-rigid Free-Form 2D-3D Registration Using Statistical Deformation Model

This paper presents a non-rigid free-from 2D-3D registration approach using statistical deformation model (SDM). In our approach the SDM is first constructed from a set of training data using a non-rigid registration algorithm based on b-spline free-form deformation to encode a priori information about the underlying anatomy. A novel intensity-based non-rigid 2D-3D registration algorithm is then presented to iteratively fit the 3D b-spline-based SDM to the 2D X-ray images of an unseen subject, which requires a computationally expensive inversion of the instantiated deformation in each iteration. In this paper, we propose to solve this challenge with a fast B-spline pseudo-inversion algorithm that is implemented on graphics processing unit (GPU). Experiments conducted on C-arm and X-ray images of cadaveric femurs demonstrate the efficacy of the present approach.

Super-Resolution in Respiratory Synchronized Positron Emission Tomography

Respiratory motion is a major source of reduced quality in positron emission tomography (PET). In order to minimize its effects, the use of respiratory synchronized acquisitions, leading to gated frames, has been suggested. Such frames, however, are of low signal-to-noise ratio (SNR) as they contain reduced statistics. Super-resolution (SR) techniques make use of the motion in a sequence of images in order to improve their quality. They aim at enhancing a low-resolution image belonging to a sequence of images representing different views of the same scene. In this work, a maximum a posteriori (MAP) super-resolution algorithm has been implemented and applied to respiratory gated PET images for motion compensation. An edge preserving Huber regularization term was used to ensure convergence. Motion fields were recovered using a B-spline based elastic registration algorithm. The performance of the SR algorithm was evaluated through the use of both simulated and clinical datasets by assessing image SNR, as well as the contrast, position and extent of the different lesions. Results were compared to summing the registered synchronized frames on both simulated and clinical datasets. The super-resolution image had higher SNR (by a factor of over 4 on average) and lesion contrast (by a factor of 2) than the single respiratory synchronized frame using the same reconstruction matrix size. In comparison to the motion corrected or the motion free images a similar SNR was obtained, while improvements of up to 20% in the recovered lesion size and contrast were measured. Finally, the recovered lesion locations on the SR images were systematically closer to the true simulated lesion positions. These observations concerning the SNR, lesion contrast and size were confirmed on two clinical datasets included in the study. In conclusion, the use of SR techniques applied to respiratory motion synchronized images lead to motion compensation combined with improved image SNR and contrast, without any increase in the overall acquisition times.

MBIS: Multivariate Bayesian Image Segmentation Tool

We present MBIS (Multivariate Bayesian Image Segmentation tool), a clustering tool based on the mixture of multivariate normal distributions model. MBIS supports multi-channel bias field correction based on a B-spline model. A second methodological novelty is the inclusion of graph-cuts optimization for the stationary anisotropic hidden Markov random field model. Along with MBIS, we release an evaluation framework that contains three different experiments on multi-site data. We first validate the accuracy of segmentation and the estimated bias field for each channel. MBIS outperforms a widely used segmentation tool in a cross-comparison evaluation. The second experiment demonstrates the robustness of results on atlas-free segmentation of two image sets from scan-rescan protocols on 21 healthy subjects. Multivariate segmentation is more replicable than the monospectral counterpart on T1-weighted images. Finally, we provide a third experiment to illustrate how MBIS can be used in a large-scale study of tissue volume change with increasing age in 584 healthy subjects. This last result is meaningful as multivariate segmentation performs robustly without the need for prior knowledge.

Parametric Generation of Planing Hulls with NURBS Surfaces

This article presents a mathematical method for producing hard-chine ship hulls based on a set of numerical parameters that are directly related to the geometric features of the hull and uniquely define a hull form for this type of ship. The term planing hull is used generically to describe the majority of hard-chine boats being built today. This article is focused on unstepped, single-chine hulls. B-spline curves and surfaces were combined with constraints on the significant ship curves to produce the final hull design. The hard-chine hull geometry was modeled by decomposing the surface geometry into boundary curves, which were defined by design constraints or parameters. In planing hull design, these control curves are the center, chine, and sheer lines as well as their geometric features including position, slope, and, in the case of the chine, enclosed area and centroid. These geometric parameters have physical, hydrodynamic, and stability implications from the design point of view. The proposed method uses two-dimensional orthogonal projections of the control curves and then produces three-dimensional (3-D) definitions using B-spline fitting of the 3-D data points. The fitting considers maximum deviation from the curve to the data points and is based on an original selection of the parameterization. A net of B-spline curves (stations) is then created to match the previously defined 3-D boundaries. A final set of lofting surfaces of the previous B-spline curves produces the hull surface.

Regression models with MoPs Bayesian networks

We present a model of Bayesian network for continuous variables, where densities and conditional densities are estimated with B-spline MoPs. We use a novel approach to directly obtain conditional densities estimation using B-spline properties. In particular we implement naive Bayes and wrapper variables selection. Finally we apply our techniques to the problem of predicting neurons morphological variables from electrophysiological ones.