Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Three dimensional study to quantify the relationship between facial hard and soft tissue movement as a result of orthognathic surgery

Introduction Prediction of soft tissue changes following orthognathic surgery has been frequently attempted in the past decades. It has gradually progressed from the classic “cut and paste” of photographs to the computer assisted 2D surgical prediction planning; and finally, comprehensive 3D surgical planning was introduced to help surgeons and patients to decide on the magnitude and direction of surgical movements as well as the type of surgery to be considered for the correction of facial dysmorphology. A wealth of experience was gained and numerous published literature is available which has augmented the knowledge of facial soft tissue behaviour and helped to improve the ability to closely simulate facial changes following orthognathic surgery. This was particularly noticed following the introduction of the three dimensional imaging into the medical research and clinical applications. Several approaches have been considered to mathematically predict soft tissue changes in three dimensions, following orthognathic surgery. The most common are the Finite element model and Mass tensor Model. These were developed into software packages which are currently used in clinical practice. In general, these methods produce an acceptable level of prediction accuracy of soft tissue changes following orthognathic surgery. Studies, however, have shown a limited prediction accuracy at specific regions of the face, in particular the areas around the lips. Aims The aim of this project is to conduct a comprehensive assessment of hard and soft tissue changes following orthognathic surgery and introduce a new method for prediction of facial soft tissue changes.   Methodology The study was carried out on the pre- and post-operative CBCT images of 100 patients who received their orthognathic surgery treatment at Glasgow dental hospital and school, Glasgow, UK. Three groups of patients were included in the analysis; patients who underwent Le Fort I maxillary advancement surgery; bilateral sagittal split mandibular advancement surgery or bimaxillary advancement surgery. A generic facial mesh was used to standardise the information obtained from individual patient’s facial image and Principal component analysis (PCA) was applied to interpolate the correlations between the skeletal surgical displacement and the resultant soft tissue changes. The identified relationship between hard tissue and soft tissue was then applied on a new set of preoperative 3D facial images and the predicted results were compared to the actual surgical changes measured from their post-operative 3D facial images. A set of validation studies was conducted. To include: • Comparison between voxel based registration and surface registration to analyse changes following orthognathic surgery. The results showed there was no statistically significant difference between the two methods. Voxel based registration, however, showed more reliability as it preserved the link between the soft tissue and skeletal structures of the face during the image registration process. Accordingly, voxel based registration was the method of choice for superimposition of the pre- and post-operative images. The result of this study was published in a refereed journal. • Direct DICOM slice landmarking; a novel technique to quantify the direction and magnitude of skeletal surgical movements. This method represents a new approach to quantify maxillary and mandibular surgical displacement in three dimensions. The technique includes measuring the distance of corresponding landmarks digitized directly on DICOM image slices in relation to three dimensional reference planes. The accuracy of the measurements was assessed against a set of “gold standard” measurements extracted from simulated model surgery. The results confirmed the accuracy of the method within 0.34mm. Therefore, the method was applied in this study. The results of this validation were published in a peer refereed journal. • The use of a generic mesh to assess soft tissue changes using stereophotogrammetry. The generic facial mesh played a major role in the soft tissue dense correspondence analysis. The conformed generic mesh represented the geometrical information of the individual’s facial mesh on which it was conformed (elastically deformed). Therefore, the accuracy of generic mesh conformation is essential to guarantee an accurate replica of the individual facial characteristics. The results showed an acceptable overall mean error of the conformation of generic mesh 1 mm. The results of this study were accepted for publication in peer refereed scientific journal. Skeletal tissue analysis was performed using the validated “Direct DICOM slices landmarking method” while soft tissue analysis was performed using Dense correspondence analysis. The analysis of soft tissue was novel and produced a comprehensive description of facial changes in response to orthognathic surgery. The results were accepted for publication in a refereed scientific Journal. The main soft tissue changes associated with Le Fort I were advancement at the midface region combined with widening of the paranasal, upper lip and nostrils. Minor changes were noticed at the tip of the nose and oral commissures. The main soft tissue changes associated with mandibular advancement surgery were advancement and downward displacement of the chin and lower lip regions, limited widening of the lower lip and slight reversion of the lower lip vermilion combined with minimal backward displacement of the upper lip were recorded. Minimal changes were observed on the oral commissures. The main soft tissue changes associated with bimaxillary advancement surgery were generalized advancement of the middle and lower thirds of the face combined with widening of the paranasal, upper lip and nostrils regions. In Le Fort I cases, the correlation between the changes of the facial soft tissue and the skeletal surgical movements was assessed using PCA. A statistical method known as ’Leave one out cross validation’ was applied on the 30 cases which had Le Fort I osteotomy surgical procedure to effectively utilize the data for the prediction algorithm. The prediction accuracy of soft tissue changes showed a mean error ranging between (0.0006mm±0.582) at the nose region to (-0.0316mm±2.1996) at the various facial regions.

Cell-cell communication in three dimensional microenvironments

Cellular behavior is dependent on a variety of extracellular cues required for normal tissue function, wound healing, and activation of the immune system. Removed from their in vivo microenvironment and cultured in vitro, cells lose many environmental cues and that may result in abberant behavior, making it difficult to study cellular processes. In order to mimic native tissue environments, optical tweezer and microfluidic technologies were used to place cells within defined areas of the culture environment. To provide three dimensional supports found in natural tissues, hydrogel scaffolds of poly (ethylene glycol) diacrylate and the basement membrane matrix Matrigel were used. Optical tweezer technology allowed precision placement and formation of homotypic and heterotypic arrays of human U937, HEK 293, and porcine mesenchymal stem cells. Alternatively, two microfluidic devices were designed to pattern Matrigel scaffolds. The first microfluidic device utilized laminar flow to spatially pattern multiple cell types within the device. Gradients of soluble molecules were then be formed and manipulated across the Matrigel scaffolds. Patterning Matrigel using laminar flow techniques require microfluidic expertise and do not produce consistent patterning conditions, limiting their use difficult in most cell culture laboratories. Thus, a buried Matrigel polydimethylsiloxane (PDMS) device was developed for spatial patterning of biological scaffolds. Matrigel is injected into micron sized channels of PDMS fabricated by soft lithography and allowed to thermally cure. Following curing, a second PDMS device was placed on top of the buried Matrigel channels to support media flow. In order to validate these systems, a cell-cell communication model system was developed utilizing LPS and TNFα signaling with fluorescent reporter systems to monitor communication in real time. We demonstrated the utility of microfluidic devices to support the cell-cell communication model system by co culturing three cell types within Matrigel scaffolds and monitoring signaling activity via fluorescent reporters.

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Fully Anisotropic Solution of the Three Dimensional Boltzmann Transport Equation

The development of accurate modeling techniques for nanoscale thermal transport is an active area of research. Modern day nanoscale devices have length scales of tens of nanometers and are prone to overheating, which reduces device performance and lifetime. Therefore, accurate temperature profiles are needed to predict the reliability of nanoscale devices. The majority of models that appear in the literature obtain temperature profiles through the solution of the Boltzmann transport equation (BTE). These models often make simplifying assumptions about the nature of the quantized energy carriers (phonons). Additionally, most previous work has focused on simulation of planar two dimensional structures. This thesis presents a method which captures the full anisotropy of the Brillouin zone within a three dimensional solution to the BTE. The anisotropy of the Brillouin zone is captured by solving the BTE for all vibrational modes allowed by the Born Von-Karman boundary conditions.

A three-dimensional representation method for noisy point clouds based on growing self-organizing maps accelerated on GPUs

The research described in this thesis was motivated by the need of a robust model capable of representing 3D data obtained with 3D sensors, which are inherently noisy. In addition, time constraints have to be considered as these sensors are capable of providing a 3D data stream in real time. This thesis proposed the use of Self-Organizing Maps (SOMs) as a 3D representation model. In particular, we proposed the use of the Growing Neural Gas (GNG) network, which has been successfully used for clustering, pattern recognition and topology representation of multi-dimensional data. Until now, Self-Organizing Maps have been primarily computed offline and their application in 3D data has mainly focused on free noise models, without considering time constraints. It is proposed a hardware implementation leveraging the computing power of modern GPUs, which takes advantage of a new paradigm coined as General-Purpose Computing on Graphics Processing Units (GPGPU). The proposed methods were applied to different problem and applications in the area of computer vision such as the recognition and localization of objects, visual surveillance or 3D reconstruction.

Noninvasive imaging of three-dimensional micro and nanostructures by topological methods

We present topological derivative and energy based procedures for the imaging of micro and nano structures using one beam of visible light of a single wavelength. Objects with diameters as small as 10 nm can be located and their position tracked with nanometer precision. Multiple objects dis-tributed either on planes perpendicular to the incidence direction or along axial lines in the incidence direction are distinguishable. More precisely, the shape and size of plane sections perpendicular to the incidence direction can be clearly determined, even for asymmetric and nonconvex scatterers. Axial resolution improves as the size of the objects decreases. Initial reconstructions may proceed by gluing together two-dimensional horizontal slices between axial peaks or by locating objects at three-dimensional peaks of topological energies, depending on the effective wavenumber. Below a threshold size, topological derivative based iterative schemes improve initial predictions of the lo-cation, size, and shape of objects by postprocessing fixed measured data. For larger sizes, tracking the peaks of topological energy fields that average information from additional incident light beams seems to be more effective.

Three-dimensional kinetic adaptations of gait throughout pregnancy and postpartum

Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.

Critical behavior of the three-dimensional Ising spin glass

We have simulated, using parallel tempering, the three-dimensional Ising spin glass model with binary couplings in a helicoidal geometry. The largest lattice (L520) has been studied using a dedicated computer (the SUE machine). We have obtained, measuring the correlation length in the critical region, strong evidence for a second-order finite-temperature phase transition, ruling out other possible scenarios like a KosterlitzThouless phase transition. Precise values for the ν and ƞ critical exponents are also presented.

Critical behavior in the site-diluted three-dimensional three-state Potts model

We have studied numerically the effect of quenched site dilution on a weak first-order phase transition in three dimensions. We have simulated the site diluted three-states Potts model studying in detail the secondorder region of its phase diagram. We have found that the n exponent is compatible with the one of the three-dimensional diluted Ising model, whereas the h exponent is definitely different.

Three-dimensional kinetic adaptations of gait throughout pregnancy and postpartum

Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.

Vortex evolution in the wake of accelerating low-aspect-ratio plates and three-dimensional bodies of revolution

To find examples of effecient locomotion and manoeuvrability, one need only turn to the elegant solutions natural flyers and swimmers have converged upon. This dissertation is specifically motivated by processes of evolutionary convergence, which have led to the propulsors and body shapes in nature that exhibit strong geometric collapse over diverse scales. These body features are abstracted in the studies presented herein using low-aspect-ratio at plates and a three-dimensional body of revolution (a sphere). The highly-separated vortical wakes that develop during accelerations are systematically characterized as a function of planform shape, aspect ratio, Reynolds number, and initial boundary conditions. To this end, force measurements and time-resolved (planar) particle image velocimetry have been used throughout to quantify the instantaneous forces and vortex evolution in the wake of the bluff bodies. During rectilinear motions, the wake development for the flat plates is primarily dependent on plate aspect ratio, with edge discontinuities and curvature playing only a secondary role. Furthermore, the axisymmetric case, i.e. the circular plate, shows strong sensitivity to Reynolds number, while this sensitivity quickly diminishes with increasing aspect ratio. For rotational motions, global insensitivity to plate aspect ratio has been observed. For the sphere, it has been shown that accelerations play an important role in the mitigation of flow separation. These results - expounded upon in this dissertation - have begun to shed light on the specific vortex dynamics that may be coopted by flying and swimming species of all shapes and sizes towards efficient locomotion.

In vitro characterization of the three-dimensional strain pattern in human vertebrae affected by metastases

La colonna vertebrale è la principale sede di metastasi, le quali possono alterare la normale distribuzione dei tessuti ossei e ridurre la capacità della vertebra di sostenere carichi. L’instabilità spinale causata dalle metastasi, tuttavia, è di difficile determinazione. La caratterizzazione meccanica delle vertebre metastatiche permetterebbe di identificare e, di conseguenza trattare, quelle ad alto rischio di frattura. In questo studio, ho valutato il comportamento meccanico a rottura di vertebre umane affette da metastasi misurando in vitro il campo di deformazione. Undici provini, costituiti da due vertebre centrali, una metastatica e una sana, sono stati preparati e scansionati applicando carichi graduali di compressione in una micro-tomografia computerizzata (μCT). Le deformazioni principali sono state misurate attraverso un algoritmo globale di Digital Volume Correlation (DVC) e successivamente sono state analizzate. Lo studio ha rivelato che le vertebre con metastasi litiche raggiungono deformazioni maggiori delle vertebre sane. Invece, le metastasi miste non assicurano un comportamento univoco in quanto combinano gli effetti antagonisti delle lesioni litiche e blastiche. Dunque la valutazione è stata estesa a possibili correlazioni tra il campo di deformazione e la microstruttura della vertebra. L'analisi ha identificato le regioni in cui parte la frattura (a più alta deformazione), senza identificare, in termini microstrutturali, una zona preferenziale di rottura a priori. Infatti, alcune zone con un pattern trabecolare denso, presunte più rigide, hanno mostrato deformazioni maggiori di quelle dei tessuti sani, sottolineando l’importanza della valutazione della qualità del tessuto osseo. Questi risultati, generalizzati su un campione più ampio, potrebbero essere utilizzati per implementare nuovi criteri negli attuali sistemi di valutazione dell'instabilità spinale.

The three-dimensional single-bin-size bin packing problem: combining metaheuristic and machine learning approaches

The Three-Dimensional Single-Bin-Size Bin Packing Problem is one of the most studied problem in the Cutting & Packing category. From a strictly mathematical point of view, it consists of packing a finite set of strongly heterogeneous “small” boxes, called items, into a finite set of identical “large” rectangles, called bins, minimizing the unused volume and requiring that the items are packed without overlapping. The great interest is mainly due to the number of real-world applications in which it arises, such as pallet and container loading, cutting objects out of a piece of material and packaging design. Depending on these real-world applications, more objective functions and more practical constraints could be needed. After a brief discussion about the real-world applications of the problem and a exhaustive literature review, the design of a two-stage algorithm to solve the aforementioned problem is presented. The algorithm must be able to provide the spatial coordinates of the placed boxes vertices and also the optimal boxes input sequence, while guaranteeing geometric, stability, fragility constraints and a reduced computational time. Due to NP-hard complexity of this type of combinatorial problems, a fusion of metaheuristic and machine learning techniques is adopted. In particular, a hybrid genetic algorithm coupled with a feedforward neural network is used. In the first stage, a rich dataset is created starting from a set of real input instances provided by an industrial company and the feedforward neural network is trained on it. After its training, given a new input instance, the hybrid genetic algorithm is able to run using the neural network output as input parameter vector, providing as output the optimal solution. The effectiveness of the proposed works is confirmed via several experimental tests.

Uno studio dell'anatomia in 3 D per l'ingegneria biomedica

Il progresso tecnologico permette l’introduzione di sempre più nuove risorse e sistemi virtuali nel campo dell’ingegneria biomedica e della medicina. La Anatomage Table 7.0 (Anatomage Inc., San Jose, CA, USA) si presenta, ad oggi, come un dispositivo d’avanguardia. Utilizzato principalmente per l’insegnamento e lo studio tridimensionale di anatomia, fisiologia e istologia del corpo umano, mediante riproduzioni reali e ad alta definizione di ogni sezione corporea, potrebbe diventare utile e d’innovazione anche per il settore biomedicale. Per investigare il suo possibile utilizzo nel campo della biomedica, sono state analizzate le funzioni principali di questo tavolo anatomico. La ricerca non ha riguardato solo la parte anatomica, ma soprattutto la cinematica e la corposa Case library, che permette uno studio approfondito di numerose patologie, attraverso simulazioni ed esami caricati nell’applicazione TableEDU 8.0.2. Inoltre, per dare un esempio delle numerose capacità di questo device medico, sono andato a studiare l’articolazione di ginocchio, avendo la possibilità di utilizzare immagini DICOM di esami reali e la simulazione di un intervento coronario percutaneo. Questo ha permesso di evidenziare tutte le potenzialità di questo tavolo anatomico e di riflettere su nuove possibilità di utilizzo nel campo della biomedica.