Quantitative structure-activity relationships for a series of inhibitors of cruzain from Trypanosoma cruzi: Molecular modeling, CoMFA and CoMSIA studies

Human parasitic diseases are the foremost threat to human health and welfare around the world. Trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. Therefore, there is an urgent need for new chemotherapeutic agents. One attractive drug target is the major cysteine protease from Trypanosoma cruzi, cruzain. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted on a series of thiosemicarbazone and semicarbazone derivatives as inhibitors of cruzain. Molecular modeling studies were performed in order to identify the preferred binding mode of the inhibitors into the enzyme active site, and to generate structural alignments for the three-dimensional quantitative structure-activity relationship (3D QSAR) investigations. Statistically significant models were obtained (CoMFA. r(2) = 0.96 and q(2) = 0.78; CoMSIA, r(2) = 0.91 and q(2) = 0.73), indicating their predictive ability for untested compounds. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the information gathered from the 3D CoMFA and CoMSIA contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of cruzain inhibitors, and should be useful for the design of new structurally related analogs with improved potency. (C) 2009 Elsevier Inc. All rights reserved.

Structure-Based Approach for the Study of Estrogen Receptor Binding Affinity and Subtype Selectivity

Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpa (hER alpha) and beta (hER beta). Because the levels and relative proportion of hER alpha and hER beta differ significantly in different target cells, selective hER ligands could target specific tissues or pathways regulated by one receptor subtype without affecting the other. To understand the structural and chemical basis by which small molecule modulators are able to discriminate between the two subtypes, we have applied three-dimensional target-based approaches employing a series of potent hER-ligands. Comparative molecular field analysis (CoMFA) studies were applied to a data set of 81 hER modulators, for which binding affinity values were collected for both hER alpha and hER beta. Significant statistical coefficients were obtained (hER alpha, q(2) = 0.76; hER beta, q(2) = 0.70), indicating the internal consistency of the models. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. Five hER crystal structures were used in GRID/PCA investigations to generate molecular interaction fields (MIF) maps. hER alpha and hER beta were separated using one factor. The resulting 3D information was integrated with the aim of revealing the most relevant structural features involved in hER subtype selectivity. The final QSAR and GRID/PCA models and the information gathered from 3D contour maps should be useful for the design or novel hER modulators with improved selectivity.

Temporomandibular joint condylar changes following maxillomandibular advancement and articular disc repositioning

Purpose To evaluate condylar changes 1 year after bimaxillary surgical advancement with or without articular disc repositioning using longitudinal quantitative measurements in 3-dimensional (3D) temporomandibular joint (TMJ) models. Methods Twenty-seven patients treated with maxillomandibular advancement (MMA) underwent cone-beam computed tomography before surgery, immediately after surgery, and at 1-year follow-up. All patients underwent magnetic resonance imaging before surgery to assess disc displacements. Ten patients without disc displacement received MMA only. Seventeen patients with articular disc displacement received MMA with simultaneous TMJ disc repositioning (MMA-Drep). Pre- and postsurgical 3D models were superimposed using a voxel-based registration on the cranial base. Results The location, direction, and magnitude of condylar changes were displayed and quantified by graphic semitransparent overlays and 3D color-coded surface distance maps. Rotational condylar displacements were similar in the 2 groups. Immediately after surgery, condylar translational displacements of at least 1.5 mm occurred in a posterior, superior, or mediolateral direction in patients treated with MMA, whereas patients treated with MMA-Drep presented more marked anterior, inferior, and mediolateral condylar displacements. One year after surgery, more than half the patients in the 2 groups presented condylar resorptive changes of at least 1.5 mm. Patients treated with MMA-Drep presented condylar bone apposition of at least 1.5 mm at the superior surface in 26.4%, the anterior surface in 23.4%, the posterior surface in 29.4%, the medial surface in 5.9%, or the lateral surface in 38.2%, whereas bone apposition was not observed in patients treated with MMA. Conclusions One year after surgery, condylar resorptive changes greater than 1.5 mm were observed in the 2 groups. Articular disc repositioning facilitated bone apposition in localized condylar regions in patients treated with MMA-Drep. © 2013 American Association of Oral and Maxillofacial Surgeons.

Modelo petrofísico 3D do Arenito Namorado no Campo de Namorado - Bacia de Campos, RJ

The Namorado Oil Field represents the beginning of the oil exploration in Brazil, in the 70s, and it is still a subject of researches because the importance of this turbidite sandstone in the brazilian oil production. The Namorado’s production level was denominated “Namorado sandstone”, it is composed by turbidite sandstone deposited during the Albian-Cenomanian. In order to define the structural geometry of the main reservoir, geological and geophysical tools like RECON and Geographix (Prizm – Seisvision) softwares were used, and its application was focused on geological facies analysis, for that propose well logs, seismic interpretation and petrophysical calculations were applied. Along this work 15 vertical wells were used and the facies reservoirs were mapped of along the oil field; it is important to mentioned that the all the facies were calibrated by the correlation rock vs log profile, and 12 reservoir-levels (NA-1, NA-2, NA-3, NA-4, NA-5, NA-6, NA-7, NA-8, NA-9, NA-10, NA-11 e NA-12) were recognized and interpreted. Stratigraphic sections (NE-SW and NW-SE) were also built based on stratigraphic well correlation of each interpreted level, and seismic interpretation (pseudo-3D seismic data) on the southeastern portion of the oil field. As results it was interpreted on two- and three-dimensional maps that the deposition reservoir’s levels are hight controlled by normal faults systems. This research also shows attribute maps interpretation and its relationship with the selection of the reservoir attribute represented on it. Finally the data integration of stratigraphic, geophysical and petrophysical calculations lets us the possibility of obtain a detail geological/petrophysical 3D model of the main reservoir levels of “Namorado sandstone” inside the oil/gás field

Preferência por marcos em mapas 3D de sistema de navegação e guia de rota em automóvel

Pós-graduação em Ciências Cartográficas - FCT

Interactive quadrangulation with reeb atlases and connectivity textures

Creating high-quality quad meshes from triangulated surfaces is a highly nontrivial task that necessitates consideration of various application specific metrics of quality. In our work, we follow the premise that automatic reconstruction techniques may not generate outputs meeting all the subjective quality expectations of the user. Instead, we put the user at the center of the process by providing a flexible, interactive approach to quadrangulation design. By combining scalar field topology and combinatorial connectivity techniques, we present a new framework, following a coarse to fine design philosophy, which allows for explicit control of the subjective quality criteria on the output quad mesh, at interactive rates. Our quadrangulation framework uses the new notion of Reeb atlas editing, to define with a small amount of interactions a coarse quadrangulation of the model, capturing the main features of the shape, with user prescribed extraordinary vertices and alignment. Fine grain tuning is easily achieved with the notion of connectivity texturing, which allows for additional extraordinary vertices specification and explicit feature alignment, to capture the high-frequency geometries. Experiments demonstrate the interactivity and flexibility of our approach, as well as its ability to generate quad meshes of arbitrary resolution with high-quality statistics, while meeting the user's own subjective requirements.

Regularization of 3D cylindrical surfaces

[EN] In this paper we present a method for the regularization of 3D cylindrical surfaces. By a cylindrical surface we mean a 3D surface that can be expressed as an application S(l; µ) ! R3 , where (l; µ) represents a cylindrical parametrization of the 3D surface. We built an initial cylindrical parametrization of the surface. We propose a new method to regularize such cylindrical surface. This method takes into account the information supplied by the disparity maps computed between pair of images to constraint the regularization of the set of 3D points. We propose a model based on an energy which is composed of two terms: an attachment term that minimizes the difference between the image coordinates and the disparity maps and a second term that enables a regularization by means of anisotropic diffusion. One interesting advantage of this approach is that we regularize the 3D surface by using a bi-dimensional minimization problem.

Study of the circulation processes in the northern Adriatic sea - coastal area and Venice lagoon inlets

This work is a detailed study of hydrodynamic processes in a defined area, the littoral in front of the Venice Lagoon and its inlets, which are complex morphological areas of interconnection. A finite element hydrodynamic model of the Venice Lagoon and the Adriatic Sea has been developed in order to study the coastal current patterns and the exchanges at the inlets of the Venice Lagoon. This is the first work in this area that tries to model the interaction dynamics, running together a model for the lagoon and the Adriatic Sea. First the barotropic processes near the inlets of the Venice Lagoon have been studied. Data from more than ten tide gauges displaced in the Adriatic Sea have been used in the calibration of the simulated water levels. To validate the model results, empirical flux data measured by ADCP probes installed inside the inlets of Lido and Malamocco have been used and the exchanges through the three inlets of the Venice Lagoon have been analyzed. The comparison between modelled and measured fluxes at the inlets outlined the efficiency of the model to reproduce both tide and wind induced water exchanges between the sea and the lagoon. As a second step, also small scale processes around the inlets that connect the Venice lagoon with the Northern Adriatic Sea have been investigated by means of 3D simulations. Maps of vorticity have been produced, considering the influence of tidal flows and wind stress in the area. A sensitivity analysis has been carried out to define the importance of the advection and of the baroclinic pressure gradients in the development of vortical processes seen along the littoral close to the inlets. Finally a comparison with real data measurements, surface velocity data from HF Radar near the Venice inlets, has been performed, which allows for a better understanding of the processes and their seasonal dynamics. The results outline the predominance of wind and tidal forcing in the coastal area. Wind forcing acts mainly on the mean coastal current inducing its detachment offshore during Sirocco events and an increase of littoral currents during Bora events. The Bora action is more homogeneous on the whole coastal area whereas the Sirocco strengthens its impact in the South, near Chioggia inlet. Tidal forcing at the inlets is mainly barotropic. The sensitivity analysis shows how advection is the main physical process responsible for the persistent vortical structures present along the littoral between the Venice Lagoon inlets. The comparison with measurements from HF Radar not only permitted a validation the model results, but also a description of different patterns in specific periods of the year. The success of the 2D and the 3D simulations on the reproduction both of the SSE, inside and outside the Venice Lagoon, of the tidal flow, through the lagoon inlets, and of the small scale phenomena, occurring along the littoral, indicates that the finite element approach is the most suitable tool for the investigation of coastal processes. For the first time, as shown by the flux modeling, the physical processes that drive the interaction between the two basins were reproduced.

Use of a 3D perfusion bioreactor with osteoblasts and osteoblast/endothelial cell co-cultures to improve tissue-engineered bone

The delivery of oxygen, nutrients, and the removal of waste are essential for cellular survival. Culture systems for 3D bone tissue engineering have addressed this issue by utilizing perfusion flow bioreactors that stimulate osteogenic activity through the delivery of oxygen and nutrients by low-shear fluid flow. It is also well established that bone responds to mechanical stimulation, but may desensitize under continuous loading. While perfusion flow and mechanical stimulation are used to increase cellular survival in vitro, 3D tissue-engineered constructs face additional limitations upon in vivo implantation. As it requires significant amounts of time for vascular infiltration by the host, implants are subject to an increased risk of necrosis. One solution is to introduce tissue-engineered bone that has been pre-vascularized through the co-culture of osteoblasts and endothelial cells on 3D constructs. It is unclear from previous studies: 1) how 3D bone tissue constructs will respond to partitioned mechanical stimulation, 2) how gene expression compares in 2D and in 3D, 3) how co-cultures will affect osteoblast activity, and 4) how perfusion flow will affect co-cultures of osteoblasts and endothelial cells. We have used an integrated approach to address these questions by utilizing mechanical stimulation, perfusion flow, and a co-culture technique to increase the success of 3D bone tissue engineering. We measured gene expression of several osteogenic and angiogenic genes in both 2D and 3D (static culture and mechanical stimulation), as well as in 3D cultures subjected to perfusion flow, mechanical stimulation and partitioned mechanical stimulation. Finally, we co-cultured osteoblasts and endothelial cells on 3D scaffolds and subjected them to long-term incubation in either static culture or under perfusion flow to determine changes in gene expression as well as histological measures of osteogenic and angiogenic activity. We discovered that 2D and 3D osteoblast cultures react differently to shear stress, and that partitioning mechanical stimulation does not affect gene expression in our model. Furthermore, our results suggest that perfusion flow may rescue 3D tissue-engineered constructs from hypoxic-like conditions by reducing hypoxia-specific gene expression and increasing histological indices of both osteogenic and angiogenic activity. Future research to elucidate the mechanisms behind these results may contribute to a more mature bone-like structure that integrates more quickly into host tissue, increasing the potential of bone tissue engineering.

Isopach Maps and Discussion of the Ordovician and Devonian of Montana and Adjacent Areas

The intensive postwar search for new petroleum horizons has resulted in widespread prospecting in the northern Great Plains. No commercial production has as yet been derived from Ordovician or Devonian rocks in Montana, but the relat­ively few tests that have penetrated to critical depths have disclosed encouraging conditions which merit further consider­ation, especially in Devonian strata.

Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

Intervertebral disc (IVD) cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC) is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5) by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

Mechanical Loading Promoted Discogenic Differentiation of Human Mesenchymal Stem Cells Incorporated in 3D-PEG Scaffolds with RhGDF5 and RGD

Hydrogels have been described as ideal scaffolds for cells of 3D tissue constructs and hold strong promises with respect to in vitro 3D-cell-culture, where cells are isolated from native extracellular matrix (ECM). Synthesized polyethyleneglycol (PEG) hydrogels are appealing with regard to potential for cell therapy or as vehicles for drug delivery or even to regenerate tissue with similar hydrogel-like properties such as the nucleus pulposus of the intervertebral disc (IVD). Here, we tested whether incorporation of RGD motive would hinder discogenic differentiation of primary bone marrow-derived human mesenchymal stem cells (hMSCs) but favor proliferation of undifferentiated hMSCs. HMSCs were embedded in +RGD containing or without RGD PEG hydrogel and pre-conditioned with or without growth and differentiation factor-5 (rhGDF-5) for 13 days. Afterwards, all hMSCs-PEG gels were subsequently cyclically loaded (15% strain, 1Hz) for 5 consecutive days in a bioreactor to generate an IVD-like phenotype. Higher metabolic activity (resazurin assay) was found in groups with rhGDF5 in both gel types with and without RGD. Cell viability and morphology measured by confocal laser microscopy and DNA content showed decreased values (~60%) after 18 days of culture. Real-time RT-PCR of an array of 15 key genes suspected to be distinctive for IVD cells revealed moderate response to rhGDF5 and mechanical loading as also shown by histology staining. Preconditioning and mechanical loading showed relatively moderate responses revealed from both RT-PCR and histology although hMSCs were demonstrated to be potent to differentiate into chondrocyte-progenitor cells in micro- mass and 3D alginate bead culture.

Accuracy of linear measurements using three imaging modalities: two lateral cephalograms and one 3D model from CBCT data

BACKGROUND The aim of this study was to evaluate the accuracy of linear measurements on three imaging modalities: lateral cephalograms from a cephalometric machine with a 3 m source-to-mid-sagittal-plane distance (SMD), from a machine with 1.5 m SMD and 3D models from cone-beam computed tomography (CBCT) data. METHODS Twenty-one dry human skulls were used. Lateral cephalograms were taken, using two cephalometric devices: one with a 3 m SMD and one with a 1.5 m SMD. CBCT scans were taken by 3D Accuitomo® 170, and 3D surface models were created in Maxilim® software. Thirteen linear measurements were completed twice by two observers with a 4 week interval. Direct physical measurements by a digital calliper were defined as the gold standard. Statistical analysis was performed. RESULTS Nasion-Point A was significantly different from the gold standard in all methods. More statistically significant differences were found on the measurements of the 3 m SMD cephalograms in comparison to the other methods. Intra- and inter-observer agreement based on 3D measurements was slightly better than others. LIMITATIONS Dry human skulls without soft tissues were used. Therefore, the results have to be interpreted with caution, as they do not fully represent clinical conditions. CONCLUSIONS 3D measurements resulted in a better observer agreement. The accuracy of the measurements based on CBCT and 1.5 m SMD cephalogram was better than a 3 m SMD cephalogram. These findings demonstrated the linear measurements accuracy and reliability of 3D measurements based on CBCT data when compared to 2D techniques. Future studies should focus on the implementation of 3D cephalometry in clinical practice.

Exploring Cultural Heritage Resources in a 3D Collaborative Environment

Cultural heritage is a complex and diverse concept, which brings together a wide domain of information. Resources linked to a cultural heritage site may consist of physical artefacts, books, works of art, pictures, historical maps, aerial photographs, archaeological surveys and 3D models. Moreover, all these resources are listed and described by a set of a variety of metadata specifications that allow their online search and consultation on the most basic characteristics of them. Some examples include Norma ISO 19115, Dublin Core, AAT, CDWA, CCO, DACS, MARC, MoReq, MODS, MuseumDat, TGN, SPECTRUM, VRA Core and Z39.50. Gateways are in place to fit in these metadata standards into those used in a SDI (ISO 19115 or INSPIRE), but substantial work still remains to be done for the complete incorporation of cultural heritage information. Therefore, the aim of this paper is to demonstrate how the complexity of cultural heritage resources can be dealt with by a visual exploration of their metadata within a 3D collaborative environment. The 3D collaborative environments are promising tools that represent the new frontier of our capacity of learning, understanding, communicating and transmitting culture.

Interpersonal relations and nurses' job satisfaction through knowledge and usage of relational skills

Background/rationale: Many interpersonal labor disputes stem from the lack of communication skills and the relational problems in the interactions between health professionals. Aims/methods: A qualitative study was conducted in a Spanish hospital in order to get to know how the communicative interaction between hospital nurses is like in relation to the nurses' interpersonal interaction and communication skills developed in their working relationships. Twenty-one hospital nurses between 29 and 55 years old, working in different wards, were interviewed. Open-ended interview discourses were transcribed verbatim and analyzed using qualitative content analysis. Results: The following four key themes were analyzed: communication and sender; communication and awareness of who has the problem; non-verbal communication; communication and recipient. Conclusion: The results of this study highlight the need to broaden nurses' relational–communication skills in order to increase job satisfaction.