Reducing Tumour Volume Uncertainty for the Benefit of Radiation Therapy Cancer Patients

The efficacy of radiotherapy is dependent on its precision and accuracy. Increasingly conformal, modulated radiation fields can be reproducibly delivered to small, complex volumes within the human body. However, treatment is not without uncertainty. This thesis focuses on limitations in radiotherapy accuracy due to uncertainty in delineation of the volume requiring treatment

Study of spacecraft direct readout meteorological systems

Characteristics are defined of the next generation direct readout meteorological satellite system with particular application to Tiros N. Both space and ground systems are included. The recommended space system is composed of four geosynchronous satellites and two low altitude satellites in sun-synchronous orbit. The goesynchronous satellites transmit to direct readout ground stations via a shared S-band link, relayed FOFAX satellite cloud cover pictures (visible and infrared) and weather charts (WEFAX). Basic sensor data is transmitted to regional Data Utilization Stations via the same S-band link. Basic sensor data consists of 0.5 n.m. sub-point resolution data in the 0.55 - 0.7 micron spectral region, and 4.0 n.m. resolution data in the 10.5 - 12.6 micron spectral region. The two low altitude satellites in sun-synchronous orbit provide data to direct readout ground stations via a 137 MHz link, a 400 Mhz link, and an S-band link

Dynamical models and machine learning for supervised segmentation

This thesis is concerned with the problem of how to outline regions of interest in medical images, when the boundaries are weak or ambiguous and the region shapes are irregular. The focus on machine learning and interactivity leads to a common theme of the need to balance conflicting requirements. First, any machine learning method must strike a balance between how much it can learn and how well it generalises. Second, interactive methods must balance minimal user demand with maximal user control. To address the problem of weak boundaries,methods of supervised texture classification are investigated that do not use explicit texture features. These methods enable prior knowledge about the image to benefit any segmentation framework. A chosen dynamic contour model, based on probabilistic boundary tracking, combines these image priors with efficient modes of interaction. We show the benefits of the texture classifiers over intensity and gradient-based image models, in both classification and boundary extraction. To address the problem of irregular region shape, we devise a new type of statistical shape model (SSM) that does not use explicit boundary features or assume high-level similarity between region shapes. First, the models are used for shape discrimination, to constrain any segmentation framework by way of regularisation. Second, the SSMs are used for shape generation, allowing probabilistic segmentation frameworks to draw shapes from a prior distribution. The generative models also include novel methods to constrain shape generation according to information from both the image and user interactions. The shape models are first evaluated in terms of discrimination capability, and shown to out-perform other shape descriptors. Experiments also show that the shape models can benefit a standard type of segmentation algorithm by providing shape regularisers. We finally show how to exploit the shape models in supervised segmentation frameworks, and evaluate their benefits in user trials

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Konturni regulator za precizne slijedne sustave

This paper discusses the trajectory generation algorithm, contour error construction method and finally the contour controller design. In the trajectory generation algorithm combination of elliptical Fourier descriptors (EFD) and time based spline approximation (TBSA) is used to generate position, velocity and acceleration references. Contour error is constructed using transformation of trajectory tracking errors. Transformation is computationally efficient and requires only reference velocity information. Contour controller is designed using sliding mode control. Experiments are performed on planar linear motion stage and significant contour error reduction is observed.U članku se raspravlja o algoritmu za generiranje trajektorija, metodi za konstrukciju pogreške konture te o sintezi konturnog regulatora. U algoritum za generiranje trajektorija, korištena je kombinacija eliptičnih Fourierovih odrednika (EFD) i vremenske aproksimacije splajnovima (TBSA) za odre.ivanje referentnih vrijednosti položaja, brzine i ubrzanja. Pogreška konture je konstruirana korištenjem transformirane pogreške slije.enja trajektorije. Transformacija je računski efikasna i potrebna joj je samo informacija o referentnoj brzini. Konturni regulator je projektiran koristeći upravljanje u kliznim režimima. Provedeni su eksperimenti na linearnom slijednom sustavu i primijećena su znatna smanjenja pogreške konture

ON THE MEASUREMENT OF A COSMOLOGICAL DIPOLE IN THE PHOTON NUMBER COUNTS OF GAMMA-RAY BURSTS

If gamma-ray bursts are cosmological or in a halo distribution their properties are expected to be isotropic (at least to 1st order). However, our motion with respect to the burst parent population (whose proper frame is expected to be that of the Cosmic Microwave Background (CMB), or that of a static halo) will cause a dipole effect in the distribution of bursts and in their photon number counts (together termed a Compton-Getting effect). We argue that the photon number count information is necessary to distinguish a genuine Compton-Getting effect from some other anisotropy and to fully test the proper frame isotropy of the bursts. Using the 2B burst catalogue and the dipole determined from the CMB, we find the surprising result that although the number weighted distribution is consistent with isotropy, the fluence weighted dipole has a correlation with the CMB dipole that has a probability of occuring only 10% of the time for an isotropic photon distribution. Furthermore, the photon and number dipoles are inconsistent under the hypothesis of isotropy, at the 2-sigma level. This could be an indication that a non-negligible fraction of gamma-ray bursts originate in the local, anisotropic universe. (shortened Abstract)Comment: Accepted by ApJ. Self-unpacking (use csh), uuencoded, compressed Postscript, 16 pages + 4 Figures (5 files

Assistive control for non-contact machining of random shaped contours

Recent achievements in robotics and automation technology has opened the door towards different machining methodologies based on material removal. Considering the non force feedback nature of non-contact machining methods, careful attention on motion control design is a primary requirement for successful achievement of precise cutting both in machining and in surgery processes. This thesis is concerned with the design of pre-processing methods and motion control techniques to provide both automated and human-assistive non-contact machining of random and complex shaped contours. In that sense, the first part of the thesis focuses on extraction of contours and generation of reference trajectories or constraints for the machining system. Based on generated trajectories, two different control schemes are utilized for high precision automated machining. In the first scheme, preview control is adopted for enhancing the tracking performance. In the second scheme, control action is generated based on direct computation of contouring error in the operational space by introducing a new coordinate frame moving with the reference contour. Further, non-contact machining is extended for realization in a master/slave telerobotic framework to enable manual remote cutting by a human operator. With the proposed approach, the human operator (i.e. a surgeon) is limited to conduct motion within a desired virtual constraint and is equipped with the ability of adjusting the cutting depth over a that contour providing advantage for laser surgery applications. The proposed framework is experimentally tested and results of the experiments prove the applicability of proposed motion control schemes and show the validity of contributions made in the context of thesis

Evolutionary modes in protein observable space: the case of Thioredoxins

In this article, we investigated the structural and dynamical evolutionary behaviour of a set of ten thioredoxin proteins as formed by three extant forms and seven resurrected ones in laboratory. Starting from the crystallographic structures, we performed all-atom molecular dynamics simulations and compare the trajectories in terms of structural and dynamical properties. Interestingly, the structural properties related to the protein density (i.e. the number of residues divided by the excluded molecular volume) well describe the protein evolutionary behaviour. Our results also suggest that the changes in sequence as occurred during the evolution have affected the protein essential motions, allowing us to discriminate between ancient and extant proteins in terms of their dynamical behaviour. Such results are yet more evident when the bacterial, archaeal and eukaryotic thioredoxins are separately analysed