Histology of damaged acetabular cartilage in symptomatic femoroacetabular impingement: an observational analysis

This prospective study on symptomatic adult patients with femoroacetabular impingement (FAI) who underwent open surgical intervention for management was designed to identify any obvious histological differences in the damaged acetabular cartilage within different subgroups of FAI. 20 patients underwent surgical intervention following safe surgical dislocation of the hip. There were 6 cases of cam impingement, 5 cases of pincer impingement and 9 of the mixed type. Pincer impingement cases demonstrated a characteristic focal, well-circumscribed and localized area of severe damage. On the other hand, cases with cam impingement showed a diffuse area of involvement affecting a larger surface of the acetabular cartilage, with degenerative changes, superficial erosions and some discontinuities. A small biopsy specimen of the acetabular rim including bone, cartilage and labrum from the affected zone was obtained in all cases. Histological evaluation was performed under normal and polarized light microscopy. Histological findings helped corroborate the pre-operative diagnosis and also define the unique nature of impingement and specific damage according to the type of impingement.

Arthroscopic versus open cam resection in the treatment of femoroacetabular impingement

PURPOSE The purpose of this study was to evaluate if osseous correction of the femoral neck achieved arthroscopically is comparable to that achieved by surgical dislocation. METHODS We retrospectively analyzed all patients who were treated with hip arthroscopy or surgical dislocation for cam or mixed type femoroacetabular impingement (FAI) in our institution between 2006 and 2009. Inclusion criteria were complete clinical and radiologic documentation with standardized radiographs. Group 1 consisted of 66 patients (49 female patients, mean age 33.8 years) treated with hip arthroscopy. Group 2 consisted of 135 patients (91 male patients, mean age 31.2 years) treated with surgical hip dislocation. We compared the preoperative and postoperative alpha and gamma angles, as well as the triangular index. Mean follow-up was 16.7 months (range, 2 to 79 months). RESULTS In group 1, the mean alpha angle improved from 60.7° preoperatively to 47.8° postoperatively (P < .001) and the mean gamma angle improved from 47.3° to 44.5° (P < .001). Over time, the preoperative mean alpha angle increased from 56.3° in 2006 to 67.5° in 2009, whereas the postoperative mean alpha angle decreased from 51.2° in 2006 to 47.5° in 2009. In group 2, the mean alpha angle improved from 75.3° preoperatively to 44.8° postoperatively (P < .001), and the mean gamma angle improved from 65.1° to 52.2° (P < .001). Arthroscopic revision of intra-articular adhesions was performed in 4 patients (6.1%) in group 1 and 16 patients (12%) in group 2. Three patients (2.2%) in group 2 underwent revision for nonunion of the greater trochanter. CONCLUSIONS Osseous correction of cam-type FAI with hip arthroscopy is comparable to the correction achieved by surgical hip dislocation. There is a significant learning curve for hip arthroscopy, with postoperative osseous correction showing improved results with increasing surgical experience. LEVEL OF EVIDENCE Level III, retrospective comparative study.

Quantification of coronary artery stenosis with high-resolution CT in comparison with histopathology in an ex vivo study

PURPOSE To investigate the ex vivo performance of high-resolution computed tomography (CT) for quantitative assessment of percentage diameter stenosis in coronary arteries compared to histopathology. MATERIALS AND METHODS High-resolution CT was performed in 26 human heart specimens after the injection of iodinated contrast media into the coronary arteries. Coronary artery plaques were visually identified on CT images and the grade of stenosis for each plaque was measured with electronic calipers. All coronary plaques were characterized by histopathology according to the Stary classification, and the percentage of stenosis was measured. RESULTS CT depicted 84% (274/326) of all coronary plaques identified by histology. Missed plaques by CT were of Stary type I (n=31), type II (n=16), and type III (n=5). The stenosis degree significantly correlated between CT and histology (r=0.81, p<0.001). CT systematically overestimated the stenosis of calcified plaques (mean difference - 11.0 ± 9.5%, p<0.01) and systematically underestimated the stenosis of non-calcified plaques (mean difference -6.8 ± 10.4%, p<0.05), while there was no significant difference for mixed-type plaques (mean difference -0.4 ± 11.7%, p=0.85). There was a significant underestimation of stenosis degree as measured by CT for Stary II plaques (mean difference -14 ± 9%, p<0.01) and a significant overestimation for Stary VII plaques (mean difference 9 ± 10%, p<0.05), but there was no significant difference in stenosis degree between both modalities for other plaque types. CONCLUSIONS High-resolution CT reliably depicts advanced stage coronary plaques with an overall good correlation of stenosis degree compared to histology, however, the degree of stenosis is systematically overestimated in calcified and underestimated in non-calcified plaques.

Long-term storage affects adhesion between titanium and zirconia using resin cements.

PURPOSE To determine the impact of long-term storage on adhesion between titanium and zirconia using resin cements. MATERIALS AND METHODS Titanium grade 4 blocks were adhesively fixed onto zirconia disks with four resin cements: Panavia F 2.0 (Kuraray Europe), GC G-Cem (GC Europe), RelyX Unicem (3M ESPE), and SmartCem 2 (Dentsply DeguDent). Shear bond strength was determined after storage in a water bath for 24 h, 16, 90, and 150 days at 37°C, and after 6000 cycles between 5°C and 55°C. Fracture behavior was evaluated using scanning electron microscopy. RESULTS After storage for at least 90 days and after thermocycling, GC G-Cem (16.9 MPa and 15.1 MPa, respectively) and RelyX Unicem (10.8 MPa and 15.7 MPa, respectively) achieved higher shear bond strength compared to SmartCem 2 (7.1 MPa and 4.0 MPa, respectively) and Panavia F2 (4.1 MPa and 7.4 MPa, respectively). At day 150, GC G-Cem and RelyX Unicem caused exclusively mixed fractures. SmartCem 2 and Panavia F2 showed adhesive fractures in one-third of the cases; all other fractures were of mixed type. After 24 h (GC G-Cem: 26.0, RelyX Unicem: 20.5 MPa, SmartCem 2: 16.1 MPa, Panavia F2: 23.6 MPa) and 16 days (GC G-Cem: 12.8, RelyX Unicem: 14.2 MPa, SmartCem 2: 9.8 MPa, Panavia F2: 14.7 MPa) of storage, shear bond strength was similar among the four cements. CONCLUSION Long-term storage and thermocycling differentially affects the bonding of resin cement between titanium and zirconia.

Androgen receptor status is highly conserved during tumor progression of breast cancer

BACKGROUND With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. METHODS AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. RESULTS AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). CONCLUSIONS Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

Facies and diagenesis of organic matter in sediments at DSDP Leg 87

A series of upper Pliocene to Pleistocene sediment samples from DSDP Sites 582 and 583 (Nankai Trough, active margin off Japan) were investigated by organic geochemical methods including organic carbon determination, Rock- Eval pyrolysis, gas chromatography of extractable hydrocarbons, and kerogen microscopy. The organic carbon content is fairly uniform and moderately low (0.35 to 0.77%) at both sites, although accompanied by high sedimentation rates. The low organic matter concentrations are the result of the combined effect of several factors: low bioproductivity, oxic depositional environment, and dilution with lithogenic material. Organic petrography revealed a mixture of three maceral types: (1) fresh, green fluorescent alginites of aquatic origin probably transported by turbidites from the shelf edge, (2) gelified huminites and paniculate liptinites derived from the erosion of unconsolidated peat, and (3) highly reflecting inertinites derived from continental erosion. By a combination of organic petrography and Rock-Eval pyrolysis results, the organic matter is characterized as mainly type III kerogen with a slight tendency to a mixed type II-III. During Rock-Eval pyrolysis, a mineral matrix effect on the generated hydrocarbons was observed. The organic matter in all sediments has a low level of maturity (below 0.45% Rm) and has not yet reached the onset of thermal hydrocarbon generation according to several geochemical maturation parameters. This low maturity is in contrast to anomalously high extract yields at both sites and large hydrocarbon proportions in the extracts at Site 583. This contrast may be due to early generation of polar compounds and perhaps redistribution of hydrocarbons caused by subduction tectonics. Carbon isotope data of the interstitial hydrocarbon gases indicate their origin from bacterial degradation of organic matter, although only very few bacterially degraded maceral components were detected.

Técnicas y materiales de la construcción fortificada altomedieval en el centro de la Península Ibérica: métodos de análisis a través de la arqueología y la historia de la construcción

Esta tesis doctoral tiene como objeto el acercamiento histórico-constructivo a la realidad material de las fortificaciones edificadas en el centro de la Península Ibérica durante los primeros siglos de la Edad Media. El marco geográfico se extiende desde el cauce del río Duero, delimitado por los valles de sus afluentes, el Duratón, al oeste, y el Escalote al este, hasta las cumbres del Sistema Central oriental en su entronque con el Ibérico, para descender por la falda sur de la sierra hasta los valles altos del Lozoya, Jarama y Henares. Siguiendo las demarcaciones actuales, el marco de estudio ocupa parcialmente las provincias de Soria, Guadalajara, Madrid, Segovia, Burgos y Valladolid. Desde un punto de vista cronológico, el espacio temporal se inicia con la conquista musulmana de la Península Ibérica de 711 y culmina con la incorporación definitiva al reino de Castilla de las zonas estudiadas, en torno al año 1150. Se trata de un espacio de transición, tanto desde el punto de vista social como ecológico. Los territorios al sur de la sierra correspondían a los confines septentrionales de la Marca Media de al-Andalus, mientras que la falta norte, los extrema durii, fueron un territorio escasamente poblado y desorganizado, foco de la expansión de los reinos de León y Castilla y zona de conflicto con al-Andalus a principios del siglo X. Un territorio tan amplio y heterogéneo, unido a una compleja evolución histórica y social y la parquedad de las fuentes escritas, ha necesitado de un acercamiento con una metodología de tipo mixto, en la que han convergido las técnicas propias de la documentación histórica, de la arqueología y de la historia de la construcción. Esta metodología parte de un exhaustivo vaciado bibliográfico, tras lo cual se planteó una prospección arqueológica dirigida que permitió realizar un catálogo de elementos fortificados en el área de estudio susceptibles de contener fases altomedievales. Sobre cada uno de los elementos localizados se realizó una toma de datos de tipo gráfico métrico y constructivo. Cruzando los datos recabados en cada edificio con técnicas propias de la estratigrafía e historia de la construcción se identificaron y aislaron las fases de la cronología analizada. Entre las fortificaciones que evidenciaron fases altomedievales y atendiendo a su singularidad, representatividad y calidad estratigráfica se ha profundizado en el análisis de nueve casos de estudio: el conjunto fortificado de Atienza, el castillo de Cogolludo, el recinto amurallado de Buitrago de Lozoya, el castillo de Caracena, la iglesia parroquial de la Inmaculada Concepción de Mezquetillas, la alcazaba de Gormaz, la torre de San Andrés de Sepúlveda, la iglesia parroquial de San Miguel de Ayllón y la fortificación rupestre de Alcolea de las Peñas. La investigación ha servido para dos fines principales. El primero se centra en el aspecto material. En este sentido no solo se ha identificado la presencia o ausencia de fases altomedievales en cado uno de los edificio lo que ha permitido realizar una lectura territorial, la caracterización de las diferentes técnicas y materiales constructivos y valorar la posibilidad de establecer una cronotipología. El segundo se centra en aspectos históricos y sociales. La vinculación de estos restos materiales con la documentación histórica ha devenido en un medio para conocer la historia de las gentes que construyeron estos edificios, la motivación que les llevó a emprender tales proyectos, así como el contexto en el que cada una de estas fortificaciones desempeñó las funciones para las que fue creada. Este estudio ha puesto de manifiesto la ruptura que supuso la ocupación estatal de esta zona por parte del ejército cordobés desde mediados del siglo X, tanto desde el punto de vista social como constructivo. Se ha podido documentar materialmente esta ocupación tras la restauración de Medinaceli, en torno a 946, y la sucedida tras la toma de Sepúlveda por parte de Almanzor en 984, diferenciándose claramente las técnicas constructivas propias de este momento, ejecutadas directamente por talleres foráneos, procedentes de Córdoba y Toledo. La posición estratigráfica de estas fábricas diagnósticas ha permito identificar fases constructivas inmediatamente anteriores y posteriores a este momento. También se ha podido comprobar la hipótesis inicial en relación a la pérdida de conocimientos constructivos durante el final de la Antigüedad y los primeros siglos del medievo en la zona estudiada. La sillería y la explotación de canteras, así como el ciclo productivo del ladrillo por completo, son recuperados sin recurrir a un sustrato tecnológico local, propiciados de manera efímera por la ocupación califal. Cuando se produce el desmembramiento del califato a partir del año 1010 estas técnicas se vuelven a abandonar. A finales del siglo XI y principios del siglo XII se produce un nuevo cambio en la construcción, recuperándose de nuevo estas técnicas de la mano del románico y del establecimiento de la red parroquial diocesana. En una zona y periodo histórico apenas explotado por la investigación, esta tesis doctoral busca no solo establecer una metodología de trabajo sino sentar las bases para futuros estudios, tanto desde el punto de vista particular, profundizando en el estudio constructivo y estratigráfico de cada uno de los elementos recogidos, como en otros aspectos más trasversales. ABSTRACT This doctoral thesis has a constructive historical material approach to the reality of the fortifications built in the center of the Iberian Peninsula during the first centuries of the middle Ages. The geographical framework extends from the Duero´s riverbed, bounded by the valleys of its tributaries, the Duratón on the west, and the Escalote on the east, until to the peaks of the eastern Central System at its connection with the Iberian, to descend the hillside of the mountain range to the high valleys of Lozoya, Jarama and Henares. Following the current demarcations under this framework study, partially cover the provinces of Soria, Guadalajara, Madrid, Segovia, Burgos and Valladolid. From a chronological point of view, the temporal space began with the Muslim conquest of the Iberian Peninsula in 711 A.D and ends with the final incorporation into the Kingdom of Castile in the studied areas, around the year 1150 A.D. It is a transitional gathering point, both socially and ecologically. The southern territories of the Sierra or mountain range corresponded to the northern boundaries of the Middle mark of al- Andalus , while the northern missing, the extrema Durii , were a disorganized sparsely populated territory and point of the expansion of the kingdoms of Leon and Castile and zone of conflict with al- Andalus at the beginning of the tenth century. Such a wide and diverse territory, connected with a complex historical, social evolution and the lack of written sources , has required an approach with a mixed type methodology, which have converged the techniques of historical documentation of the archeology and building history. This methodology comes from a comprehensive bibliographic study, after which an archaeological survey was directed that allowed building a fortified elements ‘catalog in the study area likely to contain high medieval period phases were raised. On each of the elements located one metric data collection and constructive graphic type was performed. Checking against the data collected in each building with its own history of stratigraphy and construction techniques and finally, they were identified and isolated the timing analysis phases. Among the early medieval fortifications that showed high period Medieval phases and according to its uniqueness , representativeness and stratigraphy’s quality of the nine case studies : the fortified complex of Atienza, Cogolludo Castle, the Buitrago de Lozoya´s walled enclosure , the Caracena´s castle , the Mezquetillas´ parish church, the Gormaz´s fortress, the San Andres toser in Sepulveda, the church of San Miguel de Ayllón and the Alcolea de las Peñas´ rock fortress. This research study has served two main purposes. The first focuses on the material side. In this sense it does not only identified the presence or absence of early medieval period phases in each one of the building, which has allowed a territorial reading and the characterization of the different construction techniques and materials, but it also assess the possibility of establishing a chrono–typology. The second focuses on historical and social aspects. The bound of these materials remains with the historical documentation has become a means to know the history of the people who built these buildings, the motivation that led them to undertake such projects as well as the context in which each of these fortifications played the functions for which it was created. This study has revealed the breach that led to the state occupation of the Cordovan army in this area by since mid-tenth century, from the social point of view and also from the structural one. It has been materially document this occupation after the restoration of Medinaceli, around 946, and succeeded after taking Sepulveda by Almanzor in 984, clearly differentiating their own building techniques currently implemented directly by foreign workshops, from Cordova and Toledo. The stratigraphic position of these factories has made it possible to identify earlier and later construction phases at this time. It has also been able to verify the initial hypothesis in relation with constructive knowledge loss during late antiquity and early medieval centuries in the studied area. Also ashlar, masonries as well as the brick production is recovered without resorting to a local technological substrate, fleetingly brought about by the Caliphate occupation. When the dismemberment of the Caliphate is produced from the year 1010 these techniques were abandoned again. In the late eleventh and early twelfth century these techniques are recovered from Romanesque and a new change came, also from the establishment of the diocesan parish network. In one historical period that has been hardly exploited by research, this thesis seeks not only to establish a working methodology but lay the groundwork for future studies, both from the particular point of view, paying special attention in the constructive and stratigraphic studies of each of the evidence collected , and additionally in other more transversal aspects.

Clusters of charged residues in protein three-dimensional structures.

Statistically significant charge clusters (basic, acidic, or of mixed charge) in tertiary protein structures are identified by new methods from a large representative collection of protein structures. About 10% of protein structures show at least one charge cluster, mostly of mixed type involving about equally anionic and cationic residues. Positive charge clusters are very rare. Negative (or histidine-acidic) charge clusters often coordinate calcium, or magnesium or zinc ions [e.g., thermolysin (PDB code: 3tln), mannose-binding protein (2msb), aminopeptidase (1amp)]. Mixed-charge clusters are prominent at interchain contacts where they stabilize quaternary protein formation [e.g., glutathione S-transferase (2gst), catalase (8act), and fructose-1,6-bisphosphate aldolase (1fba)]. They are also involved in protein-protein interaction and in substrate binding. For example, the mixed-charge cluster of aspartate carbamoyl-transferase (8atc) envelops the aspartate carbonyl substrate in a flexible manner (alternating tense and relaxed states) where charge associations can vary from weak to strong. Other proteins with charge clusters include the P450 cytochrome family (BM-3, Terp, Cam), several flavocytochromes, neuraminidase, hemagglutinin, the photosynthetic reaction center, and annexin. In each case in Table 2 we discuss the possible role of the charge clusters with respect to protein structure and function.

Improving the physical status and quality of life of women treated for breast cancer: A pilot study of a structured exercise intervention

Background and Objectives: This pilot project assessed the acceptability of a mixed-type, moderate-intensity exercise programme following breast cancer treatment, and the impact on presence of lymphoedema, fitness, body composition, fatigue, mood and quality of life. Methods: Ten women completed the programme and measures of fitness (submaximal ergometer test), body composition (bio-electrical impedance), lympoedema (bio-electrical impedance and arm circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety and Depression Scale), quality of life (FACT-B) and general well-being, at baseline, completion of the programme, and 6-week and 3-month follow-up. Results: Participation in the programme caused no adverse effect on the presence of lymphoedema. There was a trend towards reduction in fatigue and improved quality of life across the testing phases. Women rated the programme extremely favourably, citing benefits of the support of other women, trained guidance, and the opportunity to experience different types of exercise. Conclusions: A mixed-type, moderate-intensity exercise program in a group format is acceptable to women following breast cancer treatment, with the potential to reduce fatigue and improve quality of life, without exacerbating or precipitating lymphoedema. This pilot work needs to be confirmed in larger randomised studies. (C) 2004 Wiley-Liss, Inc.

Random vibration of the functionally graded laminates in thermal environments

This work deals with the random free vibration of functionally graded laminates with general boundary conditions and subjected to a temperature change, taking into account the randomness in a number of independent input variables such as Young's modulus, Poisson's ratio and thermal expansion coefficient of each constituent material. Based on third-order shear deformation theory, the mixed-type formulation and a semi-analytical approach are employed to derive the standard eigenvalue problem in terms of deflection, mid-plane rotations and stress function. A mean-centered first-order perturbation technique is adopted to obtain the second-order statistics of vibration frequencies. A detailed parametric study is conducted, and extensive numerical results are presented in both tabular and graphical forms for laminated plates that contain functionally graded material which is made of aluminum and zirconia, showing the effects of scattering in thermo-clastic material constants, temperature change, edge support condition, side-to-thickness ratio, and plate aspect ratio on the stochastic characteristics of natural frequencies. (c) 2005 Elsevier B.V. All rights reserved.

Representation and parameterisation issues in genetic algorithms

A multi-chromosome GA (Multi-GA) was developed, based upon concepts from the natural world, allowing improved flexibility in a number of areas including representation, genetic operators, their parameter rates and real world multi-dimensional applications. A series of experiments were conducted, comparing the performance of the Multi-GA to a traditional GA on a number of recognised and increasingly complex test optimisation surfaces, with promising results. Further experiments demonstrated the Multi-GA's flexibility through the use of non-binary chromosome representations and its applicability to dynamic parameterisation. A number of alternative and new methods of dynamic parameterisation were investigated, in addition to a new non-binary 'Quotient crossover' mechanism. Finally, the Multi-GA was applied to two real world problems, demonstrating its ability to handle mixed type chromosomes within an individual, the limited use of a chromosome level fitness function, the introduction of new genetic operators for structural self-adaptation and its viability as a serious real world analysis tool. The first problem involved optimum placement of computers within a building, allowing the Multi-GA to use multiple chromosomes with different type representations and different operators in a single individual. The second problem, commonly associated with Geographical Information Systems (GIS), required a spatial analysis location of the optimum number and distribution of retail sites over two different population grids. In applying the Multi-GA, two new genetic operators (addition and deletion) were developed and explored, resulting in the definition of a mechanism for self-modification of genetic material within the Multi-GA structure and a study of this behaviour.

Face context interferes with local part processing in a prosopagnosic patient

We investigated the role of local and global information on perceptual encoding of faces in patient HJA, who shows prosopagnosia and visual agnosia following occipito-temporal damage. HJA and an age-matched control were tested in a simultaneous matching task which focused on detection of local changes in faces: the inversion of central parts (eyes and mouth) relative to their context (as in the Thatcher illusion). Same-different judgements were made to normal, “thatcherised” and mixed type face pairs. Whole faces (Experiment 1), or face parts (Experiment 2), were presented in upright and inverted orientations. Compared to the control, HJA was severely impaired at matching whole faces, but he improved dramatically when face parts were presented in isolation. This suggests an inhibitory influence of face context on HJAs processing of local parts and a relatively intact ability to process part-based information from a face (when context cannot interfere). Face inversion did not affect HJAs performance. A control experiment (Experiment 3) with non-face stimuli (houses) suggested that the inhibitory influence of context on HJAs performance was restricted to faces. These results indicate that contextual information in a face can have an adverse influence on the processing of local part-based information in prosopagnosia.

Visualisation of bioinformatics datasets

Analysing the molecular polymorphism and interactions of DNA, RNA and proteins is of fundamental importance in biology. Predicting functions of polymorphic molecules is important in order to design more effective medicines. Analysing major histocompatibility complex (MHC) polymorphism is important for mate choice, epitope-based vaccine design and transplantation rejection etc. Most of the existing exploratory approaches cannot analyse these datasets because of the large number of molecules with a high number of descriptors per molecule. This thesis develops novel methods for data projection in order to explore high dimensional biological dataset by visualising them in a low-dimensional space. With increasing dimensionality, some existing data visualisation methods such as generative topographic mapping (GTM) become computationally intractable. We propose variants of these methods, where we use log-transformations at certain steps of expectation maximisation (EM) based parameter learning process, to make them tractable for high-dimensional datasets. We demonstrate these proposed variants both for synthetic and electrostatic potential dataset of MHC class-I. We also propose to extend a latent trait model (LTM), suitable for visualising high dimensional discrete data, to simultaneously estimate feature saliency as an integrated part of the parameter learning process of a visualisation model. This LTM variant not only gives better visualisation by modifying the project map based on feature relevance, but also helps users to assess the significance of each feature. Another problem which is not addressed much in the literature is the visualisation of mixed-type data. We propose to combine GTM and LTM in a principled way where appropriate noise models are used for each type of data in order to visualise mixed-type data in a single plot. We call this model a generalised GTM (GGTM). We also propose to extend GGTM model to estimate feature saliencies while training a visualisation model and this is called GGTM with feature saliency (GGTM-FS). We demonstrate effectiveness of these proposed models both for synthetic and real datasets. We evaluate visualisation quality using quality metrics such as distance distortion measure and rank based measures: trustworthiness, continuity, mean relative rank errors with respect to data space and latent space. In cases where the labels are known we also use quality metrics of KL divergence and nearest neighbour classifications error in order to determine the separation between classes. We demonstrate the efficacy of these proposed models both for synthetic and real biological datasets with a main focus on the MHC class-I dataset.

Mathematical Modeling and Simulation of Radial Temperature Profile of Strontium Bromide Lasers

For metal and metal halide vapor lasers excited by high frequency pulsed discharge, the thermal effect mainly caused by the radial temperature distribution is of considerable importance for stable laser operation and improvement of laser output characteristics. A short survey of the obtained analytical and numerical-analytical mathematical models of the temperature profile in a high-powered He-SrBr2 laser is presented. The models are described by the steady-state heat conduction equation with mixed type nonlinear boundary conditions for the arbitrary form of the volume power density. A complete model of radial heat flow between the two tubes is established for precise calculating the inner wall temperature. The models are applied for simulating temperature profiles for newly designed laser. The author’s software prototype LasSim is used for carrying out the mathematical models and simulations.

Quasi-Regular Solutions for 3D Equations of Tricomi and Keldish Types

Цветан Д. Христов, Недю Ив. Попиванов, Манфред Шнайдер - Изучени са някои тримерни гранични задачи за уравнения от смесен тип. За уравнения от типа на Трикоми те са формулирани от М. Протер през 1952, като тримерни аналози на задачите на Дарбу или Коши–Гурса в равнината. Добре известно е, че новите задачи са некоректни. Ние формулираме нова гранична задача за уравнения от типа на Келдиш и даваме понятие за квазиругулярно решение на тази задача и на eдна от задачите на Протер. Намерени са достатъчни условия за единственост на такива решения.